Completed

NCT Number: NCT04622709

Pilot Study of Loop Diuretics Among Individuals Receiving Hemodialysis

Individuals with kidney failure receiving maintenance hemodialysis (HD) have high mortality rates, driven largely by cardiovascular causes. Volume-related factors are critical, modifiable contributors to cardiovascular complications. Reversing volume overload has been shown to improve blood pressure and cardiac remodeling. Use of loop diuretics may represent a pragmatic, low-cost, and low-burden strategy to improve outcomes in people receiving HD. Lack of data on optimal furosemide dosing, safety, and acceptability are barriers to expanded use. This study investigates whether oral furosemide is safe and effective at increasing urine volume in HD patients.

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Key information

Conditions

Chronic Kidney Disease Requiring Chronic Dialysis Chronic Disease Disease Attributes Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Kidney Diseases Kidney Failure, Chronic Male Urogenital Diseases Pathologic Processes Pathological Conditions, Signs and Symptoms Renal Insufficiency Renal Insufficiency, Chronic Urogenital Diseases Urologic Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Carolina Dialysis - Carrboro, Carrboro, North Carolina, United States

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

Patient self-report of at least 1 cup urine/24-hours
Age ≥18 years
Receipt of thrice weekly in-center HD at a participating clinic (UNC-associated Carolina Dialysis- Carrboro, Siler City, Pittsboro, Sanford, and Lee County)
≥60 days receiving in-center HD
Willingness to take study medication and undergo study testing
Ability to provide informed consent

Exclusion criteria

Known allergy to loop diuretic
History of poor adherence to HD or medical regimen per nephrologist
>1 hospitalization in prior 30-days
Frequent hypotension (systolic BP <80 mmHg at >30% of HD treatments in prior 30-days)
Cirrhosis per nephrologist
Hearing disorder per nephrologist
Serum potassium <3.5 mEq/L, magnesium <1 mg/dL, or corrected calcium <8 mg/dL in prior 30-days
Taking a non-loop diuretic (e.g. spironolactone, eplerenone, ethacrynic acid, thiazides)
Taking an aminoglycoside, cisplatin, methotrexate, cyclosporine, adrenocorticotropic hormone (ACTH), lithium, phenytoin, or oral/intravenous steroid
Natural licorice consumption
Prisoners, patients with significant mental illness
Pregnant patients and nursing mothers

Treatment and study plan

Furosemide (loop diuretic) Tablets

Drug

Open label dose escalation study of furosemide in people receiving maintenance hemodialysis. Participants will take furosemide oral tablets twice daily for 18 weeks. Doses will be titrated every 2 weeks for 6 weeks if safe, effective, tolerated, and accepted by the participant. First 2 weeks of the study: participants not taking oral furosemide at enrollment will take 80mg furosemide twice daily, those taking oral furosemide at enrollment will stay on their prescribed dose, and those taking another loop diuretic at enrollment will discontinue their prescription and take an equivalent oral furosemide dose. At week 4: dose escalation if tolerated (from 80mg to 120mg twice daily for the 1st group, and a 50% increased dose not >320mg/day for the 2nd & 3rd groups). At week 6: dose escalation if tolerated (from 120mg to 160mg twice daily for the 1st group, and a 50% increased dose not >320mg/day for the 2nd & 3rd groups). Final 12 weeks: all participants will take the maximum tolerated dose.

Primary outcomes

Percentage of Participants Who Have a Defined Increase in 24-hour Urine Volume From Baseline to Week 5

Time frame: Baseline and study week 5 (5 weeks after study medication start
Participants will follow standard dialysis clinic protocols for 24-urine volume collection. Classifying participants as has having an increase in 24-hour urine volume will be contingent on the amount of urine the participant makes at baseline.
- Among participants with baseline 24-hour urine volume ≥200 mL: ≥25% increase in urine volume is considered an increase.
- Among participants with baseline 24-hour urine volume <200 mL: ≥50 mL increase in urine volume to a urine volume of at least 100 mL/24-hours is considered an increase.
The percentage of participants who have a defined increase in 24-urine volume from baseline to week 5 will be determined.
Percentage of Participants Who Have a Defined Increase in 24-hour Urine Volume From Baseline to Week 12

Time frame: Baseline and study week 12 (12 weeks after study medication start)
Participants will follow standard dialysis clinic protocols for 24-urine volume collection. Classifying participants as has having an increase in 24-hour urine volume will be contingent on the amount of urine the participant makes at baseline.
- Among participants with baseline 24-hour urine volume ≥200 mL: ≥25% increase in urine volume is considered an increase.
- Among participants with baseline 24-hour urine volume <200 mL: ≥50 mL increase in urine volume to a urine volume of at least 100 mL/24-hours is considered an increase.
The percentage of participants who have a defined increase in 24-urine volume from baseline to week 12 will be determined.
Percentage of Participants Who Have a Defined Increase in 24-hour Urine Volume From Baseline to Week 18

Time frame: Baseline and study week 18 (18 weeks after study medication start)
Participants will follow standard dialysis clinic protocols for 24-urine volume collection. Classifying participants as has having an increase in 24-hour urine volume will be contingent on the amount of urine the participant makes at baseline.
- Among participants with baseline 24-hour urine volume ≥200 mL: ≥25% increase in urine volume is considered an increase.
- Among participants with baseline 24-hour urine volume <200 mL: ≥50 mL increase in urine volume to a urine volume of at least 100 mL/24-hours is considered an increase.
The percentage of participants who have a defined increase in 24-urine volume from baseline to week 18 will be determined.
Percentage of Participants With A Serum Potassium <3.2 mEq/L at Week 1

Time frame: Study week 1 (1 week after study medication start)

Blood samples will be collected from participants prior to their dialysis treatments at the week 1 study visit. The percentage of participants who have a serum potassium <3.2 mEq/L will be determined.
Percentage of Participants With a Serum Potassium <3.2 mEq/L at Week 2

Time frame: Study week 2 (2 weeks after study medication start)

Blood samples will be collected from participants prior to their dialysis treatments at the week 2 study visit. The percentage of participants who have a serum potassium <3.2 mEq/L will be determined.
Percentage of Participants With a Serum Potassium <3.2 mEq/L at Week 3

Time frame: Study week 3 (3 weeks after study medication start)

Blood samples will be collected from participants prior to their dialysis treatments at the week 3 study visit. The percentage of participants who have a serum potassium <3.2 mEq/L will be determined.
Percentage of Participants With a Serum Potassium <3.2 mEq/L at Week 4

Time frame: Study week 4 (4 weeks after study medication start)

Blood samples will be collected from participants prior to their dialysis treatments at the week 4 study visit. The percentage of participants who have a serum potassium <3.2 mEq/L will be determined.
Percentage of Participants With a Serum Potassium <3.2 mEq/L at Week 5

Time frame: Study week 5 (5 weeks after study medication start)

Blood samples will be collected from participants prior to their dialysis treatments at the week 5 study visit. The percentage of participants who have a serum potassium <3.2 mEq/L will be determined.
Percentage of Participants With a Serum Potassium <3.2 mEq/L at Week 6

Time frame: Study week 6 (6 weeks after study medication start)

Blood samples will be collected from participants prior to their dialysis treatments at the week 6 study visit. The percentage of participants who have a serum potassium <3.2 mEq/L will be determined.
Percentage of Participants With a Serum Potassium <3.2 mEq/L at Week 9

Time frame: Study week 9 (9 weeks after study medication start)

Blood samples will be collected from participants prior to their dialysis treatments at the week 9 study visit. The percentage of participants who have a serum potassium <3.2 mEq/L will be determined.
Percentage of Participants With a Serum Potassium <3.2 mEq/L at Week 13

Time frame: Study week 13 (13 weeks after study medication start)

Blood samples will be collected from participants prior to their dialysis treatments at the week 13 study visit. The percentage of participants who have a serum potassium <3.2 mEq/L will be determined.
Percentage of Participants With a Serum Potassium <3.2 mEq/L at Week 17

Time frame: Study week 17 (17 weeks after study medication start)

Blood samples will be collected from participants prior to their dialysis treatments at the week 17 study visit. The percentage of participants who have a serum potassium <3.2 mEq/L will be determined.
Percentage of Participants With a Serum Magnesium <0.8 mEq/L at Week 1

Time frame: Study week 1 (1 week after study medication start)

Blood samples will be collected from participants prior to their dialysis treatments at the week 1 study visit. The percentage of participants who have a serum magnesium <0.8 mEq/L will be determined.
Percentage of Participants With a Serum Magnesium <0.8 mEq/L at Week 2

Time frame: Study week 2 (2 weeks after study medication start)

Blood samples will be collected from participants prior to their dialysis treatments at the week 2 study visit. The percentage of participants who have a serum magnesium <0.8 mEq/L will be determined.
Percentage of Participants With a Serum Magnesium <0.8 mEq/L at Week 3

Time frame: Study week 3 (3 weeks after study medication start)

Blood samples will be collected from participants prior to their dialysis treatments at the week 3 study visit. The percentage of participants who have a serum magnesium <0.8 mEq/L will be determined.
Percentage of Participants With a Serum Magnesium <0.8 mEq/L at Week 4

Time frame: Study week 4 (4 weeks after study medication start)

Blood samples will be collected from participants prior to their dialysis treatments at the week 4 study visit. The percentage of participants who have a serum magnesium <0.8 mEq/L will be determined.
Percentage of Participants With a Serum Magnesium <0.8 mEq/L at Week 5

Time frame: Study week 5 (5 weeks after study medication start)

Blood samples will be collected from participants prior to their dialysis treatments at the week 5 study visit. The percentage of participants who have a serum magnesium <0.8 mEq/L will be determined.
Percentage of Participants With a Serum Magnesium <0.8 mEq/L at Week 6

Time frame: Study week 6 (6 weeks after study medication start)

Blood samples will be collected from participants prior to their dialysis treatments at the week 6 study visit. The percentage of participants who have a serum magnesium <0.8 mEq/L will be determined.
Percentage of Participants With a Serum Magnesium <0.8 mEq/L at Week 9

Time frame: Study week 9 (9 weeks after study medication start)

Blood samples will be collected from participants prior to their dialysis treatments at the week 9 study visit. The percentage of participants who have a serum magnesium <0.8 mEq/L will be determined.
Percentage of Participants With a Serum Magnesium <0.8 mEq/L at Week 13

Time frame: Study week 13 (13 weeks after study medication start)

Blood samples will be collected from participants prior to their dialysis treatments at the week 13 study visit. The percentage of participants who have a serum magnesium <0.8 mEq/L will be determined.
Percentage of Participants With a Serum Magnesium <0.8 mEq/L at Week 17

Time frame: Study week 17 (17 weeks after study medication start)

Blood samples will be collected from participants prior to their dialysis treatments at the week 17 study visit. The percentage of participants who have a serum magnesium <0.8 mEq/L will be determined.
Percentage of Participants With a Serum Corrected Calcium <7.0 mg/dL at Week 1

Time frame: Study week 1 (1 week after study medication start)

Blood samples will be collected from participants prior to their dialysis treatments at the week 1 study visit. The percentage of participants who have a serum corrected calcium <7.0 mg/dL will be determined.
Percentage of Participants With a Serum Corrected Calcium <7.0 mg/dL at Week 2

Time frame: Study week 2 (2 weeks after study medication start)

Blood samples will be collected from participants prior to their dialysis treatments at the week 2 study visit. The percentage of participants who have a serum corrected calcium <7.0 mg/dL will be determined.
Percentage of Participants With a Serum Corrected Calcium <7.0 mg/dL at Week 3

Time frame: Study week 3 (3 weeks after study medication start)

Blood samples will be collected from participants prior to their dialysis treatments at the week 3 study visit. The percentage of participants who have a serum corrected calcium <7.0 mg/dL will be determined.
Percentage of Participants With a Serum Corrected Calcium <7.0 mg/dL at Week 4

Time frame: Study week 4 (4 weeks after study medication start)

Blood samples will be collected from participants prior to their dialysis treatments at the week 4 study visit. The percentage of participants who have a serum corrected calcium <7.0 mg/dL will be determined.
Percentage of Participants With a Serum Corrected Calcium <7.0 mg/dL at Week 5

Time frame: Study week 5 (5 weeks after study medication start)

Blood samples will be collected from participants prior to their dialysis treatments at the week 5 study visit. The percentage of participants who have a serum corrected calcium <7.0 mg/dL will be determined.
Percentage of Participants With a Serum Corrected Calcium <7.0 mg/dL at Week 6

Time frame: Study week 6 (6 weeks after study medication start)

Blood samples will be collected from participants prior to their dialysis treatments at the week 6 study visit. The percentage of participants who have a serum corrected calcium <7.0 mg/dL will be determined.
Percentage of Participants With a Serum Corrected Calcium <7.0 mg/dL at Week 9

Time frame: Study week 9 (9 weeks after study medication start)

Blood samples will be collected from participants prior to their dialysis treatments at the week 9 study visit. The percentage of participants who have a serum corrected calcium <7.0 mg/dL will be determined.
Percentage of Participants With a Serum Corrected Calcium <7.0 mg/dL at Week 13

Time frame: Study week 13 (13 weeks after study medication start)

Blood samples will be collected from participants prior to their dialysis treatments at the week 13 study visit. The percentage of participants who have a serum corrected calcium <7.0 mg/dL will be determined.
Percentage of Participants With a Serum Corrected Calcium <7.0 mg/dL at Week 17

Time frame: Study week 17 (17 weeks after study medication start)

Blood samples will be collected from participants prior to their dialysis treatments at the week 17 study visit. The percentage of participants who have a serum corrected calcium <7.0 mg/dL will be determined.
Percentage of Participants With a Serum Furosemide Level >12 Micrograms/L at Week 1.

Time frame: Study week 1 (1 week after study medication start)

Blood samples will be collected from participants prior to their dialysis treatments at the week 1 study visit. The percentage of participants who have a serum furosemide level >12 micrograms/L will be determined.
Percentage of Participants With a Serum Furosemide Level >12 Micrograms/L at Week 2.

Time frame: Study week 2 (2 weeks after study medication start)

Blood samples will be collected from participants prior to their dialysis treatments at the week 2 study visit. The percentage of participants who have a serum furosemide level >12 micrograms/L will be determined.
Percentage of Participants With a Serum Furosemide Level >12 Micrograms/L at Week 3.

Time frame: Study week 3 (3 weeks after study medication start)

Blood samples will be collected from participants prior to their dialysis treatments at the week 3 study visit. The percentage of participants who have a serum furosemide level >12 micrograms/L will be determined.
Percentage of Participants With a Serum Furosemide Level >12 Micrograms/L at Week 4.

Time frame: Study week 4 (4 weeks after study medication start)

Blood samples will be collected from participants prior to their dialysis treatments at the week 4 study visit. The percentage of participants who have a serum furosemide level >12 micrograms/L will be determined.
Percentage of Participants With a Serum Furosemide Level >12 Micrograms/L at Week 5.

Time frame: Study week 5 (5 weeks after study medication start)

Blood samples will be collected from participants prior to their dialysis treatments at the week 5 study visit. The percentage of participants who have a serum furosemide level >12 micrograms/L will be determined.
Percentage of Participants With a Serum Furosemide Level >12 Micrograms/L at Week 6.

Time frame: Study week 6 (6 weeks after study medication start)

Blood samples will be collected from participants prior to their dialysis treatments at the week 6 study visit. The percentage of participants who have a serum furosemide level >12 micrograms/L will be determined.
Percentage of Participants With a Serum Furosemide Level >12 Micrograms/L at Week 9.

Time frame: Study week 9 (9 weeks after study medication start)

Blood samples will be collected from participants prior to their dialysis treatments at the week 9 study visit. The percentage of participants who have a serum furosemide level >12 micrograms/L will be determined.
Percentage of Participants With a Serum Furosemide Level >12 Micrograms/L at Week 13.

Time frame: Study week 13 (13 weeks after study medication start)

Blood samples will be collected from participants prior to their dialysis treatments at the week 13 study visit. The percentage of participants who have a serum furosemide level >12 micrograms/L will be determined.
Percentage of Participants With a Serum Furosemide Level >12 Micrograms/L at Week 17.

Time frame: Study week 17 (17 weeks after study medication start)

Blood samples will be collected from participants prior to their dialysis treatments at the week 17 study visit. The percentage of participants who have a serum furosemide level >12 micrograms/L will be determined.
Percentage of Participants That Experience Dialysis-associated Hypotension up to Week 1

Time frame: Up to study week 1 (1 week after study medication start)

Participants' blood pressure will be measured with an upper extremity cuff in a seated position at 15-minute intervals during each hemodialysis treatment per standard dialysis clinic protocols. Dialysis-associated hypotension will be defined as hypotension during dialysis requiring hospitalization or treatment in an emergency room and not attributable to overt sepsis, acute myocardial infarction, or other cardiovascular event (e.g. aortic dissection). The percentage of participants who have dialysis-associated hypotension up to week 1 will be determined.
Percentage of Participants That Experience Dialysis-associated Hypotension up to Week 2

Time frame: Up to study week 2 (2 weeks after study medication start)

Participants' blood pressure will be measured with an upper extremity cuff in a seated position at 15-minute intervals during each hemodialysis treatment per standard dialysis clinic protocols. Dialysis-associated hypotension will be defined as hypotension during dialysis requiring hospitalization or treatment in an emergency room and not attributable to overt sepsis, acute myocardial infarction, or other cardiovascular event (e.g. aortic dissection). The percentage of participants who have dialysis-associated hypotension up to week 2 will be determined.
Percentage of Participants That Experience Dialysis-associated Hypotension up to Week 3

Time frame: Up to study week 3 (3 weeks after study medication start)

Participants' blood pressure will be measured with an upper extremity cuff in a seated position at 15-minute intervals during each hemodialysis treatment per standard dialysis clinic protocols. Dialysis-associated hypotension will be defined as hypotension during dialysis requiring hospitalization or treatment in an emergency room and not attributable to overt sepsis, acute myocardial infarction, or other cardiovascular event (e.g. aortic dissection). The percentage of participants who have dialysis-associated hypotension up to week 3 will be determined.
Percentage of Participants That Experience Dialysis-associated Hypotension up to Week 4

Time frame: Up to study week 4 (4 weeks after study medication start)

Participants' blood pressure will be measured with an upper extremity cuff in a seated position at 15-minute intervals during each hemodialysis treatment per standard dialysis clinic protocols. Dialysis-associated hypotension will be defined as hypotension during dialysis requiring hospitalization or treatment in an emergency room and not attributable to overt sepsis, acute myocardial infarction, or other cardiovascular event (e.g. aortic dissection). The percentage of participants who have dialysis-associated hypotension up to week 4 will be determined.
Percentage of Participants That Experience Dialysis-associated Hypotension up to Week 5

Time frame: Up to study week 5 (5 weeks after study medication start)

Participants' blood pressure will be measured with an upper extremity cuff in a seated position at 15-minute intervals during each hemodialysis treatment per standard dialysis clinic protocols. Dialysis-associated hypotension will be defined as hypotension during dialysis requiring hospitalization or treatment in an emergency room and not attributable to overt sepsis, acute myocardial infarction, or other cardiovascular event (e.g. aortic dissection). The percentage of participants who have dialysis-associated hypotension up to week 5 will be determined.
Percentage of Participants That Experience Dialysis-associated Hypotension up to Week 6

Time frame: Up to study week 6 (6 weeks after study medication start)

Participants' blood pressure will be measured with an upper extremity cuff in a seated position at 15-minute intervals during each hemodialysis treatment per standard dialysis clinic protocols. Dialysis-associated hypotension will be defined as hypotension during dialysis requiring hospitalization or treatment in an emergency room and not attributable to overt sepsis, acute myocardial infarction, or other cardiovascular event (e.g. aortic dissection). The percentage of participants who have dialysis-associated hypotension up to week 6 will be determined.
Percentage of Participants That Experience Dialysis-associated Hypotension up to Week 7

Time frame: Up to study week 7 (7 weeks after study medication start)

Participants' blood pressure will be measured with an upper extremity cuff in a seated position at 15-minute intervals during each hemodialysis treatment per standard dialysis clinic protocols. Dialysis-associated hypotension will be defined as hypotension during dialysis requiring hospitalization or treatment in an emergency room and not attributable to overt sepsis, acute myocardial infarction, or other cardiovascular event (e.g. aortic dissection). The percentage of participants who have dialysis-associated hypotension up to week 7 will be determined.
Percentage of Participants That Experience Dialysis-associated Hypotension up to Week 8

Time frame: Up to study week 8 (8 weeks after study medication start)

Participants' blood pressure will be measured with an upper extremity cuff in a seated position at 15-minute intervals during each hemodialysis treatment per standard dialysis clinic protocols. Dialysis-associated hypotension will be defined as hypotension during dialysis requiring hospitalization or treatment in an emergency room and not attributable to overt sepsis, acute myocardial infarction, or other cardiovascular event (e.g. aortic dissection). The percentage of participants who have dialysis-associated hypotension up to week 8 will be determined.
Percentage of Participants That Experience Dialysis-associated Hypotension up to Week 9

Time frame: Up to study week 9 (9 weeks after study medication start)

Participants' blood pressure will be measured with an upper extremity cuff in a seated position at 15-minute intervals during each hemodialysis treatment per standard dialysis clinic protocols. Dialysis-associated hypotension will be defined as hypotension during dialysis requiring hospitalization or treatment in an emergency room and not attributable to overt sepsis, acute myocardial infarction, or other cardiovascular event (e.g. aortic dissection). The percentage of participants who have dialysis-associated hypotension up to week 9 will be determined.
Percentage of Participants That Experience Dialysis-associated Hypotension up to Week 10

Time frame: Up to study week 10 (10 weeks after study medication start)

Participants' blood pressure will be measured with an upper extremity cuff in a seated position at 15-minute intervals during each hemodialysis treatment per standard dialysis clinic protocols. Dialysis-associated hypotension will be defined as hypotension during dialysis requiring hospitalization or treatment in an emergency room and not attributable to overt sepsis, acute myocardial infarction, or other cardiovascular event (e.g. aortic dissection). The percentage of participants who have dialysis-associated hypotension up to week 10 will be determined.
Percentage of Participants That Experience Dialysis-associated Hypotension up to Week 11

Time frame: Up to study week 11 (11 weeks after study medication start)

Participants' blood pressure will be measured with an upper extremity cuff in a seated position at 15-minute intervals during each hemodialysis treatment per standard dialysis clinic protocols. Dialysis-associated hypotension will be defined as hypotension during dialysis requiring hospitalization or treatment in an emergency room and not attributable to overt sepsis, acute myocardial infarction, or other cardiovascular event (e.g. aortic dissection). The percentage of participants who have dialysis-associated hypotension up to week 11 will be determined.
Percentage of Participants That Experience Dialysis-associated Hypotension up to Week 12

Time frame: Up to study week 12 (12 weeks after study medication start)

Participants' blood pressure will be measured with an upper extremity cuff in a seated position at 15-minute intervals during each hemodialysis treatment per standard dialysis clinic protocols. Dialysis-associated hypotension will be defined as hypotension during dialysis requiring hospitalization or treatment in an emergency room and not attributable to overt sepsis, acute myocardial infarction, or other cardiovascular event (e.g. aortic dissection). The percentage of participants who have dialysis-associated hypotension up to week 12 will be determined.
Percentage of Participants That Experience Dialysis-associated Hypotension up to Week 13

Time frame: Up to study week 13 (13 weeks after study medication start)

Participants' blood pressure will be measured with an upper extremity cuff in a seated position at 15-minute intervals during each hemodialysis treatment per standard dialysis clinic protocols. Dialysis-associated hypotension will be defined as hypotension during dialysis requiring hospitalization or treatment in an emergency room and not attributable to overt sepsis, acute myocardial infarction, or other cardiovascular event (e.g. aortic dissection). The percentage of participants who have dialysis-associated hypotension up to week 13 will be determined.
Percentage of Participants That Experience Dialysis-associated Hypotension up to Week 14

Time frame: Up to study week 14 (14 weeks after study medication start)

Participants' blood pressure will be measured with an upper extremity cuff in a seated position at 15-minute intervals during each hemodialysis treatment per standard dialysis clinic protocols. Dialysis-associated hypotension will be defined as hypotension during dialysis requiring hospitalization or treatment in an emergency room and not attributable to overt sepsis, acute myocardial infarction, or other cardiovascular event (e.g. aortic dissection). The percentage of participants who have dialysis-associated hypotension up to week 14 will be determined.
Percentage of Participants That Experience Dialysis-associated Hypotension up to Week 15

Time frame: Up to study week 15 (15 weeks after study medication start)

Participants' blood pressure will be measured with an upper extremity cuff in a seated position at 15-minute intervals during each hemodialysis treatment per standard dialysis clinic protocols. Dialysis-associated hypotension will be defined as hypotension during dialysis requiring hospitalization or treatment in an emergency room and not attributable to overt sepsis, acute myocardial infarction, or other cardiovascular event (e.g. aortic dissection). The percentage of participants who have dialysis-associated hypotension up to week 15 will be determined.
Percentage of Participants That Experience Dialysis-associated Hypotension up to Week 16

Time frame: Up to study week 16 (16 weeks after study medication start)

Participants' blood pressure will be measured with an upper extremity cuff in a seated position at 15-minute intervals during each hemodialysis treatment per standard dialysis clinic protocols. Dialysis-associated hypotension will be defined as hypotension during dialysis requiring hospitalization or treatment in an emergency room and not attributable to overt sepsis, acute myocardial infarction, or other cardiovascular event (e.g. aortic dissection). The percentage of participants who have dialysis-associated hypotension up to week 16 will be determined.
Percentage of Participants That Experience Dialysis-associated Hypotension up to Week 17

Time frame: Up to study week 17 (17 weeks after study medication start)

Participants' blood pressure will be measured with an upper extremity cuff in a seated position at 15-minute intervals during each hemodialysis treatment per standard dialysis clinic protocols. Dialysis-associated hypotension will be defined as hypotension during dialysis requiring hospitalization or treatment in an emergency room and not attributable to overt sepsis, acute myocardial infarction, or other cardiovascular event (e.g. aortic dissection). The percentage of participants who have dialysis-associated hypotension up to week 17 will be determined.
Percentage of Participants That Experience Dialysis-associated Hypotension up to Week 18

Time frame: Up to study week 18 (18 weeks after study medication start)

Participants' blood pressure will be measured with an upper extremity cuff in a seated position at 15-minute intervals during each hemodialysis treatment per standard dialysis clinic protocols. Dialysis-associated hypotension will be defined as hypotension during dialysis requiring hospitalization or treatment in an emergency room and not attributable to overt sepsis, acute myocardial infarction, or other cardiovascular event (e.g. aortic dissection). The percentage of participants who have dialysis-associated hypotension up to week 18 will be determined.
Percentage of Participants Reporting a Severe or Very Severe Rash Attributable to Furosemide at Week 1

Time frame: Study week 1 (1 week after study medication start)

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 1. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious rash will be defined as rash ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting a severe or very severe rash attributable to furosemide will be determined.
Percentage of Participants Reporting a Severe or Very Severe Rash Attributable to Furosemide at Week 2

Time frame: Study week 2 (2 weeks after study medication start)

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 2. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious rash will be defined as rash ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting a severe or very severe rash attributable to furosemide will be determined.
Percentage of Participants Reporting a Severe or Very Severe Rash Attributable to Furosemide at Week 3

Time frame: Study week 3 (3 weeks after study medication start)

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 3. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious rash will be defined as rash ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting a severe or very severe rash attributable to furosemide will be determined.
Percentage of Participants Reporting a Severe or Very Severe Rash Attributable to Furosemide at Week 4

Time frame: Study week 4 (4 weeks after study medication start)

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 4. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious rash will be defined as rash ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting a severe or very severe rash attributable to furosemide will be determined.
Percentage of Participants Reporting a Severe or Very Severe Rash Attributable to Furosemide at Week 5

Time frame: Study week 5 (5 weeks after study medication start)

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 5. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious rash will be defined as rash ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting a severe or very severe rash attributable to furosemide will be determined.
Percentage of Participants Reporting a Severe or Very Severe Rash Attributable to Furosemide at Week 6

Time frame: Study week 6 (6 weeks after study medication start)

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 6. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious rash will be defined as rash ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting a severe or very severe rash attributable to furosemide will be determined.
Percentage of Participants Reporting a Severe or Very Severe Rash Attributable to Furosemide at Week 8

Time frame: Study week 8 (8 weeks after study medication start)

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 8. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious rash will be defined as rash ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting a severe or very severe rash attributable to furosemide will be determined.
Percentage of Participants Reporting a Severe or Very Severe Rash Attributable to Furosemide at Week 10

Time frame: Study week 10 (10 weeks after study medication start)

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 10. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious rash will be defined as rash ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting a severe or very severe rash attributable to furosemide will be determined.
Percentage of Participants Reporting a Severe or Very Severe Rash Attributable to Furosemide at Week 12

Time frame: Study week 12 (12 weeks after study medication start)

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 12. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious rash will be defined as rash ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting a severe or very severe rash attributable to furosemide will be determined.
Percentage of Participants Reporting a Severe or Very Severe Rash Attributable to Furosemide at Week 14

Time frame: Study week 14 (14 weeks after study medication start)

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 14. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious rash will be defined as rash ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting a severe or very severe rash attributable to furosemide will be determined.
Percentage of Participants Reporting a Severe or Very Severe Rash Attributable to Furosemide at Week 16

Time frame: Study week 16 (16 weeks after study medication start)

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 16. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious rash will be defined as rash ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting a severe or very severe rash attributable to furosemide will be determined.
Percentage of Participants Reporting a Severe or Very Severe Rash Attributable to Furosemide at Week 18

Time frame: Study week 18 (18 weeks after study medication start)

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 18. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious rash will be defined as rash ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting a severe or very severe rash attributable to furosemide will be determined.
Percentage of Participants Reporting Severe or Very Severe Tinnitus Attributable to Furosemide at Week 1

Time frame: Study week 1 (1 week after study medication start)

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 1. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious tinnitus will be defined as tinnitus ranked as severe or very severe and attributable to furosemide. Incidence will be defined as percentage of participants who have serious tinnitus. The percentage of participants reporting severe or very severe tinnitus attributable to furosemide will be determined.
Percentage of Participants Reporting Severe or Very Severe Tinnitus Attributable to Furosemide at Week 2

Time frame: Study week 2 (2 weeks after study medication start)

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 2. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious tinnitus will be defined as tinnitus ranked as severe or very severe and attributable to furosemide. Incidence will be defined as percentage of participants who have serious tinnitus. The percentage of participants reporting severe or very severe tinnitus attributable to furosemide will be determined.
Percentage of Participants Reporting Severe or Very Severe Tinnitus Attributable to Furosemide at Week 3

Time frame: Study week 3 (3 weeks after study medication start)

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 3. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious tinnitus will be defined as tinnitus ranked as severe or very severe and attributable to furosemide. Incidence will be defined as percentage of participants who have serious tinnitus. The percentage of participants reporting severe or very severe tinnitus attributable to furosemide will be determined.
Percentage of Participants Reporting Severe or Very Severe Tinnitus Attributable to Furosemide at Week 4

Time frame: Study week 4 (4 weeks after study medication start)

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 4. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious tinnitus will be defined as tinnitus ranked as severe or very severe and attributable to furosemide. Incidence will be defined as percentage of participants who have serious tinnitus. The percentage of participants reporting severe or very severe tinnitus attributable to furosemide will be determined.
Percentage of Participants Reporting Severe or Very Severe Tinnitus Attributable to Furosemide at Week 5

Time frame: Study week 5 (5 weeks after study medication start)

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 5. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious tinnitus will be defined as tinnitus ranked as severe or very severe and attributable to furosemide. Incidence will be defined as percentage of participants who have serious tinnitus. The percentage of participants reporting severe or very severe tinnitus attributable to furosemide will be determined.
Percentage of Participants Reporting Severe or Very Severe Tinnitus Attributable to Furosemide at Week 6

Time frame: Study week 6 (6 weeks after study medication start)

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 6. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious tinnitus will be defined as tinnitus ranked as severe or very severe and attributable to furosemide. Incidence will be defined as percentage of participants who have serious tinnitus. The percentage of participants reporting severe or very severe tinnitus attributable to furosemide will be determined.
Percentage of Participants Reporting Severe or Very Severe Tinnitus Attributable to Furosemide at Week 8

Time frame: Study week 8 (8 weeks after study medication start)

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 8. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious tinnitus will be defined as tinnitus ranked as severe or very severe and attributable to furosemide. Incidence will be defined as percentage of participants who have serious tinnitus. The percentage of participants reporting severe or very severe tinnitus attributable to furosemide will be determined.
Percentage of Participants Reporting Severe or Very Severe Tinnitus Attributable to Furosemide at Week 10

Time frame: Study week 10 (10 weeks after study medication start)

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 10. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious tinnitus will be defined as tinnitus ranked as severe or very severe and attributable to furosemide. Incidence will be defined as percentage of participants who have serious tinnitus. The percentage of participants reporting severe or very severe tinnitus attributable to furosemide will be determined.
Percentage of Participants Reporting Severe or Very Severe Tinnitus Attributable to Furosemide at Week 12

Time frame: Study week 12 (12 weeks after study medication start)

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 12. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious tinnitus will be defined as tinnitus ranked as severe or very severe and attributable to furosemide. Incidence will be defined as percentage of participants who have serious tinnitus. The percentage of participants reporting severe or very severe tinnitus attributable to furosemide will be determined.
Percentage of Participants Reporting Severe or Very Severe Tinnitus Attributable to Furosemide at Week 14

Time frame: Study week 14 (14 weeks after study medication start)

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 14. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious tinnitus will be defined as tinnitus ranked as severe or very severe and attributable to furosemide. Incidence will be defined as percentage of participants who have serious tinnitus. The percentage of participants reporting severe or very severe tinnitus attributable to furosemide will be determined.
Percentage of Participants Reporting Severe or Very Severe Tinnitus Attributable to Furosemide at Week 16

Time frame: Study week 16 (16 weeks after study medication start)

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 16. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious tinnitus will be defined as tinnitus ranked as severe or very severe and attributable to furosemide. Incidence will be defined as percentage of participants who have serious tinnitus. The percentage of participants reporting severe or very severe tinnitus attributable to furosemide will be determined.
Percentage of Participants Reporting Severe or Very Severe Tinnitus Attributable to Furosemide at Week 18

Time frame: Study week 18 (18 weeks after study medication start)

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 18. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious tinnitus will be defined as tinnitus ranked as severe or very severe and attributable to furosemide. Incidence will be defined as percentage of participants who have serious tinnitus. The percentage of participants reporting severe or very severe tinnitus attributable to furosemide will be determined.
Percentage of Participants Reporting a Severe or Very Severe Hearing Change Attributable to Furosemide at Week 1

Time frame: Study week 1 (1 week after study medication start)

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 1. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious hearing change will be defined as hearing change ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting a severe or very severe hearing change attributable to furosemide will be determined.
Percentage of Participants Reporting a Severe or Very Severe Hearing Change Attributable to Furosemide at Week 2

Time frame: Study week 2 (2 weeks after study medication start)

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 2. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious hearing change will be defined as hearing change ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting a severe or very severe hearing change attributable to furosemide will be determined.
Percentage of Participants Reporting a Severe or Very Severe Hearing Change Attributable to Furosemide at Week 3

Time frame: Study week 3 (3 weeks after study medication start)

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 3. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious hearing change will be defined as hearing change ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting a severe or very severe hearing change attributable to furosemide will be determined.
Percentage of Participants Reporting a Severe or Very Severe Hearing Change Attributable to Furosemide at Week 4

Time frame: Study week 4 (4 weeks after study medication start)

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 4. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious hearing change will be defined as hearing change ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting a severe or very severe hearing change attributable to furosemide will be determined.
Percentage of Participants Reporting a Severe or Very Severe Hearing Change Attributable to Furosemide at Week 5

Time frame: Study week 5 (5 weeks after study medication start)

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 5. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious hearing change will be defined as hearing change ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting a severe or very severe hearing change attributable to furosemide will be determined.
Percentage of Participants Reporting a Severe or Very Severe Hearing Change Attributable to Furosemide at Week 6

Time frame: Study week 6 (6 weeks after study medication start)

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 6. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious hearing change will be defined as hearing change ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting a severe or very severe hearing change attributable to furosemide will be determined.
Percentage of Participants Reporting a Severe or Very Severe Hearing Change Attributable to Furosemide at Week 8

Time frame: Study week 8 (8 weeks after study medication start)

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 8. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious hearing change will be defined as hearing change ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting a severe or very severe hearing change attributable to furosemide will be determined.
Percentage of Participants Reporting a Severe or Very Severe Hearing Change Attributable to Furosemide at Week 10

Time frame: Study week 10 (10 weeks after study medication start)

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 10. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious hearing change will be defined as hearing change ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting a severe or very severe hearing change attributable to furosemide will be determined.
Percentage of Participants Reporting a Severe or Very Severe Hearing Change Attributable to Furosemide at Week 12

Time frame: Study week 12 (12 weeks after study medication start)

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 12. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious hearing change will be defined as hearing change ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting a severe or very severe hearing change attributable to furosemide will be determined.
Percentage of Participants Reporting a Severe or Very Severe Hearing Change Attributable to Furosemide at Week 14

Time frame: Study week 14 (14 weeks after study medication start)

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 14. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious hearing change will be defined as hearing change ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting a severe or very severe hearing change attributable to furosemide will be determined.
Percentage of Participants Reporting a Severe or Very Severe Hearing Change Attributable to Furosemide at Week 16

Time frame: Study week 16 (16 weeks after study medication start)

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 16. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious hearing change will be defined as hearing change ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting a severe or very severe hearing change attributable to furosemide will be determined.
Percentage of Participants Reporting a Severe or Very Severe Hearing Change Attributable to Furosemide at Week 18

Time frame: Study week 18 (18 weeks after study medication start)

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 18. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious hearing change will be defined as hearing change ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting a severe or very severe hearing change attributable to furosemide will be determined.
Change in the Inner EAR Instrument Score From Baseline to Week 1

Time frame: Baseline and study week 1 (1 week after study medication start)

Participants' hearing ability during the last week will be assessed using the Inner Effectiveness of Auditory Rehabilitation (Inner EAR) 11-question validated questionnaire administered during study week 1. The total instrument score will be tallied at each administration [range: 10 (low hearing ability) - 59 (high hearing ability)]. Serious hearing change will be defined as a ≥10-point decrease in the Inner EAR instrument score from baseline score.
Percentage of Participants With a Defined Decrease in the Inner EAR Instrument Score From Baseline to Week 2

Time frame: Baseline and study week 2 (2 weeks after study medication start)

Participants' hearing ability during the last week will be assessed using the Inner Effectiveness of Auditory Rehabilitation (Inner EAR) 11-question validated questionnaire administered during study week 2. The total instrument score will be tallied at each administration [range: 10 (low hearing ability) - 59 (high hearing ability)]. Serious hearing change will be defined as a ≥10-point decrease in the Inner EAR instrument score from baseline score. The percentage of participants with a defined decrease in the Inner EAR instrument score will be determined.
Change in the Inner EAR Instrument Score From Baseline to Week 3

Time frame: Baseline and study week 3 (3 weeks after study medication start)

Participants' hearing ability during the last week will be assessed using the Inner Effectiveness of Auditory Rehabilitation (Inner EAR) 11-question validated questionnaire administered during study week 3. The total instrument score will be tallied at each administration [range: 10 (low hearing ability) - 59 (high hearing ability)]. Serious hearing change will be defined as a ≥10-point decrease in the Inner EAR instrument score from baseline score.
Percentage of Participants With a Defined Decrease in the Inner EAR Instrument Score From Baseline to Week 4

Time frame: Baseline and study week 4 (4 weeks after study medication start)

Participants' hearing ability during the last week will be assessed using the Inner Effectiveness of Auditory Rehabilitation (Inner EAR) 11-question validated questionnaire administered during study week 4. The total instrument score will be tallied at each administration [range: 10 (low hearing ability) - 59 (high hearing ability)]. Serious hearing change will be defined as a ≥10-point decrease in the Inner EAR instrument score from baseline score. The percentage of participants with a defined decrease in the Inner EAR instrument score will be determined.
Change in the Inner EAR Instrument Score From Baseline to Week 5

Time frame: Baseline and study week 5 (5 weeks after study medication start)

Participants' hearing ability during the last week will be assessed using the Inner Effectiveness of Auditory Rehabilitation (Inner EAR) 11-question validated questionnaire administered during study week 5. The total instrument score will be tallied at each administration [range: 10 (low hearing ability) - 59 (high hearing ability)]. Serious hearing change will be defined as a ≥10-point decrease in the Inner EAR instrument score from baseline score.
Percentage of Participants With a Defined Decrease in the Inner EAR Instrument Score From Baseline to Week 6

Time frame: Baseline and study week 6 (6 weeks after study medication start)

Participants' hearing ability during the last week will be assessed using the Inner Effectiveness of Auditory Rehabilitation (Inner EAR) 11-question validated questionnaire administered during study week 6. The total instrument score will be tallied at each administration [range: 10 (low hearing ability) - 59 (high hearing ability)]. Serious hearing change will be defined as a ≥10-point decrease in the Inner EAR instrument score from baseline score. The percentage of participants with a defined decrease in the Inner EAR instrument score will be determined.
Change in the Inner EAR Instrument Score From Baseline to Week 8

Time frame: Baseline and study week 8 (8 weeks after study medication start)

Participants' hearing ability during the last week will be assessed using the Inner Effectiveness of Auditory Rehabilitation (Inner EAR) 11-question validated questionnaire administered during study week 8. The total instrument score will be tallied at each administration [range: 10 (low hearing ability) - 59 (high hearing ability)]. Serious hearing change will be defined as a ≥10-point decrease in the Inner EAR instrument score from baseline score.
Percentage of Participants With a Defined Decrease in the Inner EAR Instrument Score From Baseline to Week 10

Time frame: Baseline and study week 10 (10 weeks after study medication start)

Participants' hearing ability during the last week will be assessed using the Inner Effectiveness of Auditory Rehabilitation (Inner EAR) 11-question validated questionnaire administered during study week 10. The total instrument score will be tallied at each administration [range: 10 (low hearing ability) - 59 (high hearing ability)]. Serious hearing change will be defined as a ≥10-point decrease in the Inner EAR instrument score from baseline score. The percentage of participants with a defined decrease in the Inner EAR instrument score will be determined.
Change in the Inner EAR Instrument Score From Baseline to Week 12

Time frame: Baseline and study week 12 (12 weeks after study medication start)

Participants' hearing ability during the last week will be assessed using the Inner Effectiveness of Auditory Rehabilitation (Inner EAR) 11-question validated questionnaire administered during study week 12. The total instrument score will be tallied at each administration [range: 10 (low hearing ability) - 59 (high hearing ability)]. Serious hearing change will be defined as a ≥10-point decrease in the Inner EAR instrument score from baseline score.
Percentage of Participants With a Defined Decrease in the Inner EAR Instrument Score From Baseline to Week 14

Time frame: Baseline and study week 14 (14 weeks after study medication start)

Participants' hearing ability during the last week will be assessed using the Inner Effectiveness of Auditory Rehabilitation (Inner EAR) 11-question validated questionnaire administered during study week 14. The total instrument score will be tallied at each administration [range: 10 (low hearing ability) - 59 (high hearing ability)]. Serious hearing change will be defined as a ≥10-point decrease in the Inner EAR instrument score from baseline score. The percentage of participants with a defined decrease in the Inner EAR instrument score will be determined.
Change in the Inner EAR Instrument Score From Baseline to Week 16

Time frame: Baseline and study week 16 (16 weeks after study medication start)

Participants' hearing ability during the last week will be assessed using the Inner Effectiveness of Auditory Rehabilitation (Inner EAR) 11-question validated questionnaire administered during study week 16. The total instrument score will be tallied at each administration [range: 10 (low hearing ability) - 59 (high hearing ability)]. Serious hearing change will be defined as a ≥10-point decrease in the Inner EAR instrument score from baseline score.
Percentage of Participants With a Defined Decrease in the Inner EAR Instrument Score From Baseline to Week 18

Time frame: Baseline and study week 18 (18 weeks after study medication start)

Participants' hearing ability during the last week will be assessed using the Inner Effectiveness of Auditory Rehabilitation (Inner EAR) 11-question validated questionnaire administered during study week 18. The total instrument score will be tallied at each administration [range: 10 (low hearing ability) - 59 (high hearing ability)]. Serious hearing change will be defined as a ≥10-point decrease in the Inner EAR instrument score from baseline score. The percentage of participants with a defined decrease in the Inner EAR instrument score will be determined.
Percentage of Participants Reporting Severe or Very Severe Cramping Attributable to Furosemide at Week 1

Time frame: Study week 1 (1 week after study medication start)

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 1. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious cramping will be defined as cramping ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe cramping attributable to furosemide will be determined.
Percentage of Participants Reporting Severe or Very Severe Cramping Attributable to Furosemide at Week 2

Time frame: Study week 2 (2 weeks after study medication start)

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 2. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious cramping will be defined as cramping ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe cramping attributable to furosemide will be determined.
Percentage of Participants Reporting Severe or Very Severe Cramping Attributable to Furosemide at Week 3

Time frame: Study week 3 (3 weeks after study medication start)

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 3. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious cramping will be defined as cramping ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe cramping attributable to furosemide will be determined.
Percentage of Participants Reporting Severe or Very Severe Cramping Attributable to Furosemide at Week 4

Time frame: Study week 4 (4 weeks after study medication start)

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 4. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious cramping will be defined as cramping ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe cramping attributable to furosemide will be determined.
Percentage of Participants Reporting Severe or Very Severe Cramping Attributable to Furosemide at Week 5

Time frame: Study week 5 (5 weeks after study medication start)

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 5. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious cramping will be defined as cramping ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe cramping attributable to furosemide will be determined.
Percentage of Participants Reporting Severe or Very Severe Cramping Attributable to Furosemide at Week 6

Time frame: Study week 6 (6 weeks after study medication start)

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 6. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious cramping will be defined as cramping ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe cramping attributable to furosemide will be determined.
Percentage of Participants Reporting Severe or Very Severe Cramping Attributable to Furosemide at Week 8

Time frame: Study week 8 (8 weeks after study medication start)

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 8. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious cramping will be defined as cramping ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe cramping attributable to furosemide will be determined.
Percentage of Participants Reporting Severe or Very Severe Cramping Attributable to Furosemide at Week 10

Time frame: Study week 10 (10 weeks after study medication start)

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 10. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious cramping will be defined as cramping ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe cramping attributable to furosemide will be determined.
Percentage of Participants Reporting Severe or Very Severe Cramping Attributable to Furosemide at Week 12

Time frame: Study week 12 (12 weeks after study medication start)

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 12. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious cramping will be defined as cramping ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe cramping attributable to furosemide will be determined.
Percentage of Participants Reporting Severe or Very Severe Cramping Attributable to Furosemide at Week 14

Time frame: Study week 14 (14 weeks after study medication start)

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 14. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious cramping will be defined as cramping ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe cramping attributable to furosemide will be determined.
Percentage of Participants Reporting Severe or Very Severe Cramping Attributable to Furosemide at Week 16

Time frame: Study week 16 (16 weeks after study medication start)

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 16. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious cramping will be defined as cramping ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe cramping attributable to furosemide will be determined.
Percentage of Participants Reporting Severe or Very Severe Cramping Attributable to Furosemide at Week 18

Time frame: Study week 18 (18 weeks after study medication start)

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 18. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious cramping will be defined as cramping ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe cramping attributable to furosemide will be determined.
Percentage of Participants Reporting Severe or Very Severe Dizziness/Pre-syncope Attributable to Furosemide at Week 1

Time frame: Study week 1 (1 week after study medication start)

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 1. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious dizziness/pre-syncope will be defined as dizziness/pre-syncope ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe dizziness/pre-syncope attributable to furosemide will be determined.
Percentage of Participants Reporting Severe or Very Severe Dizziness/Pre-syncope Attributable to Furosemide at Week 2

Time frame: Study week 2 (2 weeks after study medication start)

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 2. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious dizziness/pre-syncope will be defined as dizziness/pre-syncope ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe dizziness/pre-syncope attributable to furosemide will be determined.
Percentage of Participants Reporting Severe or Very Severe Dizziness/Pre-syncope Attributable to Furosemide at Week 3

Time frame: Study week 3 (3 weeks after study medication start)

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 3. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious dizziness/pre-syncope will be defined as dizziness/pre-syncope ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe dizziness/pre-syncope attributable to furosemide will be determined.
Percentage of Participants Reporting Severe or Very Severe Dizziness/Pre-syncope Attributable to Furosemide at Week 4

Time frame: Study week 4 (4 weeks after study medication start)

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 4. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious dizziness/pre-syncope will be defined as dizziness/pre-syncope ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe dizziness/pre-syncope attributable to furosemide will be determined.
Percentage of Participants Reporting Severe or Very Severe Dizziness/Pre-syncope Attributable to Furosemide at Week 5

Time frame: Study week 5 (5 weeks after study medication start)

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 5. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious dizziness/pre-syncope will be defined as dizziness/pre-syncope ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe dizziness/pre-syncope attributable to furosemide will be determined.
Percentage of Participants Reporting Severe or Very Severe Dizziness/Pre-syncope Attributable to Furosemide at Week 6

Time frame: Study week 6 (6 weeks after study medication start)

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 6. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious dizziness/pre-syncope will be defined as dizziness/pre-syncope ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe dizziness/pre-syncope attributable to furosemide will be determined.
Percentage of Participants Reporting Severe or Very Severe Dizziness/Pre-syncope Attributable to Furosemide at Week 8

Time frame: Study week 8 (8 weeks after study medication start)

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 8. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious dizziness/pre-syncope will be defined as dizziness/pre-syncope ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe dizziness/pre-syncope attributable to furosemide will be determined.
Percentage of Participants Reporting Severe or Very Severe Dizziness/Pre-syncope Attributable to Furosemide at Week 10

Time frame: Study week 10 (10 weeks after study medication start)

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 10. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious dizziness/pre-syncope will be defined as dizziness/pre-syncope ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe dizziness/pre-syncope attributable to furosemide will be determined.
Percentage of Participants Reporting Severe or Very Severe Dizziness/Pre-syncope Attributable to Furosemide at Week 12

Time frame: Study week 12 (12 weeks after study medication start)

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 12. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious dizziness/pre-syncope will be defined as dizziness/pre-syncope ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe dizziness/pre-syncope attributable to furosemide will be determined.
Percentage of Participants Reporting Severe or Very Severe Dizziness/Pre-syncope Attributable to Furosemide at Week 14

Time frame: Study week 14 (14 weeks after study medication start)

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 14. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious dizziness/pre-syncope will be defined as dizziness/pre-syncope ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe dizziness/pre-syncope attributable to furosemide will be determined.
Percentage of Participants Reporting Severe or Very Severe Dizziness/Pre-syncope Attributable to Furosemide at Week 16

Time frame: Study week 16 (16 weeks after study medication start)

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 16. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious dizziness/pre-syncope will be defined as dizziness/pre-syncope ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe dizziness/pre-syncope attributable to furosemide will be determined.
Percentage of Participants Reporting Severe or Very Severe Dizziness/Pre-syncope Attributable to Furosemide at Week 18

Time frame: Study week 18 (18 weeks after study medication start)

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 18. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious dizziness/pre-syncope will be defined as dizziness/pre-syncope ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe dizziness/pre-syncope attributable to furosemide will be determined.
Percentage of Participants Reporting Severe or Very Severe Unusual Tiredness/Weakness Attributable to Furosemide at Week 1

Time frame: Study week 1 (1 week after study medication start)

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 1. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious unusual tiredness/weakness will be defined as unusual tiredness/weakness ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe unusual tiredness/weakness will be determined.
Percentage of Participants Reporting Severe or Very Severe Unusual Tiredness/Weakness Attributable to Furosemide at Week 2

Time frame: Study week 2 (2 weeks after study medication start)

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 2. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious unusual tiredness/weakness will be defined as unusual tiredness/weakness ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe unusual tiredness/weakness will be determined.
Percentage of Participants Reporting Severe or Very Severe Unusual Tiredness/Weakness Attributable to Furosemide at Week 3

Time frame: Study week 3 (3 weeks after study medication start)

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 3. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious unusual tiredness/weakness will be defined as unusual tiredness/weakness ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe unusual tiredness/weakness will be determined.
Percentage of Participants Reporting Severe or Very Severe Unusual Tiredness/Weakness Attributable to Furosemide at Week 4

Time frame: Study week 4 (4 weeks after study medication start)

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 4. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious unusual tiredness/weakness will be defined as unusual tiredness/weakness ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe unusual tiredness/weakness will be determined.
Percentage of Participants Reporting Severe or Very Severe Unusual Tiredness/Weakness Attributable to Furosemide at Week 5

Time frame: Study week 5 (5 weeks after study medication start)

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 5. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious unusual tiredness/weakness will be defined as unusual tiredness/weakness ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe unusual tiredness/weakness will be determined.
Percentage of Participants Reporting Severe or Very Severe Unusual Tiredness/Weakness Attributable to Furosemide at Week 6

Time frame: Study week 6 (6 weeks after study medication start)

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 6. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious unusual tiredness/weakness will be defined as unusual tiredness/weakness ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe unusual tiredness/weakness will be determined.
Percentage of Participants Reporting Severe or Very Severe Unusual Tiredness/Weakness Attributable to Furosemide at Week 8

Time frame: Study week 8 (8 weeks after study medication start)

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 8. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious unusual tiredness/weakness will be defined as unusual tiredness/weakness ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe unusual tiredness/weakness will be determined.
Percentage of Participants Reporting Severe or Very Severe Unusual Tiredness/Weakness Attributable to Furosemide at Week 10

Time frame: Study week 10 (10 weeks after study medication start)

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 10. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious unusual tiredness/weakness will be defined as unusual tiredness/weakness ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe unusual tiredness/weakness will be determined.
Percentage of Participants Reporting Severe or Very Severe Unusual Tiredness/Weakness Attributable to Furosemide at Week 12

Time frame: Study week 12 (12 weeks after study medication start)

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 12. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious unusual tiredness/weakness will be defined as unusual tiredness/weakness ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe unusual tiredness/weakness will be determined.
Percentage of Participants Reporting Severe or Very Severe Unusual Tiredness/Weakness Attributable to Furosemide at Week 14

Time frame: Study week 14 (14 weeks after study medication start)

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 14. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious unusual tiredness/weakness will be defined as unusual tiredness/weakness ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe unusual tiredness/weakness will be determined.
Percentage of Participants Reporting Severe or Very Severe Unusual Tiredness/Weakness Attributable to Furosemide at Week 16

Time frame: Study week 16 (16 weeks after study medication start)

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 16. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious unusual tiredness/weakness will be defined as unusual tiredness/weakness ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe unusual tiredness/weakness will be determined.
Percentage of Participants Reporting Severe or Very Severe Unusual Tiredness/Weakness Attributable to Furosemide at Week 18

Time frame: Study week 18 (18 weeks after study medication start)

Participants' dialysis-related symptoms during the prior week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 18. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious unusual tiredness/weakness will be defined as unusual tiredness/weakness ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe unusual tiredness/weakness will be determined.
Percentage of Participants Reporting Severe or Very Severe Chest Pain Attributable to Furosemide at Week 1

Time frame: Study week 1 (1 week after study medication start)

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 1. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious chest pain will be defined as chest pain ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe chest pain will be determined.
Percentage of Participants Reporting Severe or Very Severe Chest Pain Attributable to Furosemide at Week 2

Time frame: Study week 2 (2 weeks after study medication start)

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 2. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious chest pain will be defined as chest pain ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe chest pain will be determined.
Percentage of Participants Reporting Severe or Very Severe Chest Pain Attributable to Furosemide at Week 3

Time frame: Study week 3 (3 weeks after study medication start)

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 3. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious chest pain will be defined as chest pain ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe chest pain will be determined.
Percentage of Participants Reporting Severe or Very Severe Chest Pain Attributable to Furosemide at Week 4

Time frame: Study week 4 (4 weeks after study medication start)

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 4. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious chest pain will be defined as chest pain ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe chest pain will be determined.
Percentage of Participants Reporting Severe or Very Severe Chest Pain Attributable to Furosemide at Week 5

Time frame: Study week 5 (5 weeks after study medication start)

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 5. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious chest pain will be defined as chest pain ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe chest pain will be determined.
Percentage of Participants Reporting Severe or Very Severe Chest Pain Attributable to Furosemide at Week 6

Time frame: Study week 6 (6 weeks after study medication start)

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 6. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious chest pain will be defined as chest pain ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe chest pain will be determined.
Percentage of Participants Reporting Severe or Very Severe Chest Pain Attributable to Furosemide at Week 8

Time frame: Study week 8 (8 weeks after study medication start)

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 8. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious chest pain will be defined as chest pain ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe chest pain will be determined.
Percentage of Participants Reporting Severe or Very Severe Chest Pain Attributable to Furosemide at Week 10

Time frame: Study week 10 (10 weeks after study medication start)

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 10. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious chest pain will be defined as chest pain ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe chest pain will be determined.
Percentage of Participants Reporting Severe or Very Severe Chest Pain Attributable to Furosemide at Week 12

Time frame: Study week 12 (12 weeks after study medication start)

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 12. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious chest pain will be defined as chest pain ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe chest pain will be determined.
Percentage of Participants Reporting Severe or Very Severe Chest Pain Attributable to Furosemide at Week 14

Time frame: Study week 14 (14 weeks after study medication start)

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 14. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious chest pain will be defined as chest pain ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe chest pain will be determined.
Percentage of Participants Reporting Severe or Very Severe Chest Pain Attributable to Furosemide at Week 16

Time frame: Study week 16 (16 weeks after study medication start)

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 16. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious chest pain will be defined as chest pain ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe chest pain will be determined.
Percentage of Participants Reporting Severe or Very Severe Chest Pain Attributable to Furosemide at Week 18

Time frame: Study week 18 (18 weeks after study medication start)

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 18. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious chest pain will be defined as chest pain ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe chest pain will be determined.
Percentage of Participants Reporting Severe or Very Severe Nausea Attributable to Furosemide at Week 1

Time frame: Study week 1 (1 week after study medication start)

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 1. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious nausea will be defined as nausea ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe nausea will be determined.
Percentage of Participants Reporting Severe or Very Severe Nausea Attributable to Furosemide at Week 2

Time frame: Study week 2 (2 weeks after study medication start)

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 2. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious nausea will be defined as nausea ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe nausea will be determined.
Percentage of Participants Reporting Severe or Very Severe Nausea Attributable to Furosemide at Week 3

Time frame: Study week 3 (3 weeks after study medication start)

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 3. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious nausea will be defined as nausea ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe nausea will be determined.
Percentage of Participants Reporting Severe or Very Severe Nausea Attributable to Furosemide at Week 4

Time frame: Study week 4 (4 weeks after study medication start)

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 4. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious nausea will be defined as nausea ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe nausea will be determined.
Percentage of Participants Reporting Severe or Very Severe Nausea Attributable to Furosemide at Week 5

Time frame: Study week 5 (5 weeks after study medication start)

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 5. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious nausea will be defined as nausea ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe nausea will be determined.
Percentage of Participants Reporting Severe or Very Severe Nausea Attributable to Furosemide at Week 6

Time frame: Study week 6 (6 weeks after study medication start)

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 6. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious nausea will be defined as nausea ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe nausea will be determined.
Percentage of Participants Reporting Severe or Very Severe Nausea Attributable to Furosemide at Week 8

Time frame: Study week 8 (8 weeks after study medication start)

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 8. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious nausea will be defined as nausea ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe nausea will be determined.
Percentage of Participants Reporting Severe or Very Severe Nausea Attributable to Furosemide at Week 10

Time frame: Study week 10 (10 weeks after study medication start)

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 10. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious nausea will be defined as nausea ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe nausea will be determined.
Percentage of Participants Reporting Severe or Very Severe Nausea Attributable to Furosemide at Week 12

Time frame: Study week 12 (12 weeks after study medication start)

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 12. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious nausea will be defined as nausea ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe nausea will be determined.
Percentage of Participants Reporting Severe or Very Severe Nausea Attributable to Furosemide at Week 14

Time frame: Study week 14 (14 weeks after study medication start)

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 14. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious nausea will be defined as nausea ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe nausea will be determined.
Percentage of Participants Reporting Severe or Very Severe Nausea Attributable to Furosemide at Week 16

Time frame: Study week 16 (16 weeks after study medication start)

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 16. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious nausea will be defined as nausea ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe nausea will be determined.
Percentage of Participants Reporting Severe or Very Severe Nausea Attributable to Furosemide at Week 18

Time frame: Study week 18 (18 weeks after study medication start)

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 18. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious nausea will be defined as nausea ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe nausea will be determined.
Percentage of Participants Reporting Severe or Very Severe Vomiting Attributable to Furosemide at Week 1

Time frame: Study week 1 (1 week after study medication start)

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 1. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious vomiting will be defined as vomiting ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe vomiting will be determined.
Percentage of Participants Reporting Severe or Very Severe Vomiting Attributable to Furosemide at Week 2

Time frame: Study week 2 (2 weeks after study medication start)

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 2. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious vomiting will be defined as vomiting ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe vomiting will be determined.
Percentage of Participants Reporting Severe or Very Severe Vomiting Attributable to Furosemide at Week 3

Time frame: Study week 3 (3 weeks after study medication start)

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 3. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious vomiting will be defined as vomiting ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe vomiting will be determined.
Percentage of Participants Reporting Severe or Very Severe Vomiting Attributable to Furosemide at Week 4

Time frame: Study week 4 (4 weeks after study medication start)

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 4. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious vomiting will be defined as vomiting ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe vomiting will be determined.
Percentage of Participants Reporting Severe or Very Severe Vomiting Attributable to Furosemide at Week 5

Time frame: Study week 5 (5 weeks after study medication start)

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 5. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious vomiting will be defined as vomiting ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe vomiting will be determined.
Percentage of Participants Reporting Severe or Very Severe Vomiting Attributable to Furosemide at Week 6

Time frame: Study week 6 (6 weeks after study medication start)

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 6. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious vomiting will be defined as vomiting ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe vomiting will be determined.
Percentage of Participants Reporting Severe or Very Severe Vomiting Attributable to Furosemide at Week 8

Time frame: Study week 8 (8 weeks after study medication start)

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 8. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious vomiting will be defined as vomiting ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe vomiting will be determined.
Percentage of Participants Reporting Severe or Very Severe Vomiting Attributable to Furosemide at Week 10

Time frame: Study week 10 (10 weeks after study medication start)

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 10. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious vomiting will be defined as vomiting ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe vomiting will be determined.
Percentage of Participants Reporting Severe or Very Severe Vomiting Attributable to Furosemide at Week 12

Time frame: Study week 12 (12 weeks after study medication start)

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 12. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious vomiting will be defined as vomiting ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe vomiting will be determined.
Percentage of Participants Reporting Severe or Very Severe Vomiting Attributable to Furosemide at Week 14

Time frame: Study week 14 (14 weeks after study medication start)

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 14. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious vomiting will be defined as vomiting ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe vomiting will be determined.
Percentage of Participants Reporting Severe or Very Severe Vomiting Attributable to Furosemide at Week 16

Time frame: Study week 16 (16 weeks after study medication start)

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 16. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious vomiting will be defined as vomiting ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe vomiting will be determined.
Percentage of Participants Reporting Severe or Very Severe Vomiting Attributable to Furosemide at Week 18

Time frame: Study week 18 (18 weeks after study medication start)

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 18. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious vomiting will be defined as vomiting ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe vomiting will be determined.
Percentage of Participants Reporting Severe or Very Severe Diarrhea Attributable to Furosemide at Week 1

Time frame: Study week 1 (1 week after study medication start)

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 1. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious diarrhea will be defined as diarrhea ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe diarrhea will be determined.
Percentage of Participants Reporting Severe or Very Severe Diarrhea Attributable to Furosemide at Week 2

Time frame: Study week 2 (2 weeks after study medication start)

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 2. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious diarrhea will be defined as diarrhea ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe diarrhea will be determined.
Percentage of Participants Reporting Severe or Very Severe Diarrhea Attributable to Furosemide at Week 3

Time frame: Study week 3 (3 weeks after study medication start)

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 3. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious diarrhea will be defined as diarrhea ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe diarrhea will be determined.
Percentage of Participants Reporting Severe or Very Severe Diarrhea Attributable to Furosemide at Week 4

Time frame: Study week 4 (4 weeks after study medication start)

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 4. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious diarrhea will be defined as diarrhea ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe diarrhea will be determined.
Percentage of Participants Reporting Severe or Very Severe Diarrhea Attributable to Furosemide at Week 5

Time frame: Study week 5 (5 weeks after study medication start)

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 5. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious diarrhea will be defined as diarrhea ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe diarrhea will be determined.
Percentage of Participants Reporting Severe or Very Severe Diarrhea Attributable to Furosemide at Week 6

Time frame: Study week 6 (6 weeks after study medication start)

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 6. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious diarrhea will be defined as diarrhea ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe diarrhea will be determined.
Percentage of Participants Reporting Severe or Very Severe Diarrhea Attributable to Furosemide at Week 8

Time frame: Study week 8 (8 weeks after study medication start)

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 8. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious diarrhea will be defined as diarrhea ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe diarrhea will be determined.
Percentage of Participants Reporting Severe or Very Severe Diarrhea Attributable to Furosemide at Week 10

Time frame: Study week 10 (10 weeks after study medication start)

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 10. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious diarrhea will be defined as diarrhea ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe diarrhea will be determined.
Percentage of Participants Reporting Severe or Very Severe Diarrhea Attributable to Furosemide at Week 12

Time frame: Study week 12 (12 weeks after study medication start)

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 12. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious diarrhea will be defined as diarrhea ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe diarrhea will be determined.
Percentage of Participants Reporting Severe or Very Severe Diarrhea Attributable to Furosemide at Week 14

Time frame: Study week 14 (14 weeks after study medication start)

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 14. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious diarrhea will be defined as diarrhea ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe diarrhea will be determined.
Percentage of Participants Reporting Severe or Very Severe Diarrhea Attributable to Furosemide at Week 16

Time frame: Study week 16 (16 weeks after study medication start)

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 16. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious diarrhea will be defined as diarrhea ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe diarrhea will be determined.
Percentage of Participants Reporting Severe or Very Severe Diarrhea Attributable to Furosemide at Week 18

Time frame: Study week 18 (18 weeks after study medication start)

Participants' dialysis-related symptoms during the last week will be assessed using an investigator-developed 13-question symptom questionnaire administered at study week 18. Each symptom will be graded using a 5-point symptom severity Likert scale (response options: none, mild, moderate, severe, very severe). Serious diarrhea will be defined as diarrhea ranked as severe or very severe and attributable to furosemide. The percentage of participants reporting severe or very severe diarrhea will be determined.
Percentage of Participants Reporting Acceptance of Furosemide at Week 1

Time frame: Study week 1 (1 week after study medication start)

Participants' acceptance of furosemide will be assessed using an investigator-developed 1-question questionnaire administered at study week 1. Patient-reported acceptance of furosemide at the dose during which the questionnaire is administered will be defined as an affirmative response ("yes") to the question "If recommended, would you be willing to stay on the dose of furosemide you have received during the last week?". The percentage of participants reporting acceptance of furosemide will be determined.
Percentage of Participants Reporting Acceptance of Furosemide at Week 2

Time frame: Study week 2 (2 weeks after study medication start)

Participants' acceptance of furosemide will be assessed using an investigator-developed 1-question questionnaire administered at study week 2. Patient-reported acceptance of furosemide at the dose during which the questionnaire is administered will be defined as an affirmative response ("yes") to the question "If recommended, would you be willing to stay on the dose of furosemide you have received during the last week?". The percentage of participants reporting acceptance of furosemide will be determined.
Percentage of Participants Reporting Acceptance of Furosemide at Week 3

Time frame: Study week 3 (3 weeks after study medication start)

Participants' acceptance of furosemide will be assessed using an investigator-developed 1-question questionnaire administered at study week 3. Patient-reported acceptance of furosemide at the dose during which the questionnaire is administered will be defined as an affirmative response ("yes") to the question "If recommended, would you be willing to stay on the dose of furosemide you have received during the last week?". The percentage of participants reporting acceptance of furosemide will be determined.
Percentage of Participants Reporting Acceptance of Furosemide at Week 4

Time frame: Study week 4 (4 weeks after study medication start)

Participants' acceptance of furosemide will be assessed using an investigator-developed 1-question questionnaire administered at study week 4. Patient-reported acceptance of furosemide at the dose during which the questionnaire is administered will be defined as an affirmative response ("yes") to the question "If recommended, would you be willing to stay on the dose of furosemide you have received during the last week?". The percentage of participants reporting acceptance of furosemide will be determined.
Percentage of Participants Reporting Acceptance of Furosemide at Week 5

Time frame: Study week 5 (5 weeks after study medication start)

Participants' acceptance of furosemide will be assessed using an investigator-developed 1-question questionnaire administered at study week 5. Patient-reported acceptance of furosemide at the dose during which the questionnaire is administered will be defined as an affirmative response ("yes") to the question "If recommended, would you be willing to stay on the dose of furosemide you have received during the last week?". The percentage of participants reporting acceptance of furosemide will be determined.
Percentage of Participants Reporting Acceptance of Furosemide at Week 6

Time frame: Study week 6 (6 weeks after study medication start)

Participants' acceptance of furosemide will be assessed using an investigator-developed 1-question questionnaire administered at study week 6. Patient-reported acceptance of furosemide at the dose during which the questionnaire is administered will be defined as an affirmative response ("yes") to the question "If recommended, would you be willing to stay on the dose of furosemide you have received during the last week?". The percentage of participants reporting acceptance of furosemide will be determined.
Percentage of Participants Reporting Acceptance of Furosemide at Week 8

Time frame: Study week 8 (8 weeks after study medication start)

Participants' acceptance of furosemide will be assessed using an investigator-developed 1-question questionnaire administered at study week 8. Patient-reported acceptance of furosemide at the dose during which the questionnaire is administered will be defined as an affirmative response ("yes") to the question "If recommended, would you be willing to stay on the dose of furosemide you have received during the last week?". The percentage of participants reporting acceptance of furosemide will be determined.
Percentage of Participants Reporting Acceptance of Furosemide at Week 10

Time frame: Study week 10 (10 weeks after study medication start)

Participants' acceptance of furosemide will be assessed using an investigator-developed 1-question questionnaire administered at study week 10. Patient-reported acceptance of furosemide at the dose during which the questionnaire is administered will be defined as an affirmative response ("yes") to the question "If recommended, would you be willing to stay on the dose of furosemide you have received during the last week?". The percentage of participants reporting acceptance of furosemide will be determined.
Percentage of Participants Reporting Acceptance of Furosemide at Week 12

Time frame: Study week 12 (12 weeks after study medication start)

Participants' acceptance of furosemide will be assessed using an investigator-developed 1-question questionnaire administered at study week 12. Patient-reported acceptance of furosemide at the dose during which the questionnaire is administered will be defined as an affirmative response ("yes") to the question "If recommended, would you be willing to stay on the dose of furosemide you have received during the last week?". The percentage of participants reporting acceptance of furosemide will be determined.
Percentage of Participants Reporting Acceptance of Furosemide at Week 14

Time frame: Study week 14 (14 weeks after study medication start)

Participants' acceptance of furosemide will be assessed using an investigator-developed 1-question questionnaire administered at study week 14. Patient-reported acceptance of furosemide at the dose during which the questionnaire is administered will be defined as an affirmative response ("yes") to the question "If recommended, would you be willing to stay on the dose of furosemide you have received during the last week?". The percentage of participants reporting acceptance of furosemide will be determined.
Percentage of Participants Reporting Acceptance of Furosemide at Week 16

Time frame: Study week 16 (16 weeks after study medication start)

Participants' acceptance of furosemide will be assessed using an investigator-developed 1-question questionnaire administered at study week 16. Patient-reported acceptance of furosemide at the dose during which the questionnaire is administered will be defined as an affirmative response ("yes") to the question "If recommended, would you be willing to stay on the dose of furosemide you have received during the last week?". The percentage of participants reporting acceptance of furosemide will be determined.
Percentage of Participants Reporting Acceptance of Furosemide at Week 18

Time frame: Study week 18 (18 weeks after study medication start)

Participants' acceptance of furosemide will be assessed using an investigator-developed 1-question questionnaire administered at study week 18. Patient-reported acceptance of furosemide at the dose during which the questionnaire is administered will be defined as an affirmative response ("yes") to the question "If recommended, would you be willing to stay on the dose of furosemide you have received during the last week?". The percentage of participants reporting acceptance of furosemide will be determined.
Percentage of Participants Who Are Adherent to Furosemide (<20% Pills Remaining at Scheduled Pill Counts) at Week 1

Time frame: Study week 1 (1 week after study medication start)

Participants' adherence to furosemide will be assessed at scheduled pill counts conducted by the study team at study week 1. Participants' adherence to furosemide will be defined <20% pills remaining at the scheduled pill counts. The percentage of participants who are adherent to furosemide will be determined.
Percentage of Participants Who Are Adherent to Furosemide (<20% Pills Remaining at Scheduled Pill Counts) at Week 2

Time frame: Study week 2 (2 weeks after study medication start)

Participants' adherence to furosemide will be assessed at scheduled pill counts conducted by the study team at study week 2. Participants' adherence to furosemide will be defined <20% pills remaining at the scheduled pill counts. The percentage of participants who are adherent to furosemide will be determined.
Percentage of Participants Who Are Adherent to Furosemide (<20% Pills Remaining at Scheduled Pill Counts) at Week 3

Time frame: Study week 3 (3 weeks after study medication start)

Participants' adherence to furosemide will be assessed at scheduled pill counts conducted by the study team at study week 3. Participants' adherence to furosemide will be defined <20% pills remaining at the scheduled pill counts. The percentage of participants who are adherent to furosemide will be determined.
Percentage of Participants Who Are Adherent to Furosemide (<20% Pills Remaining at Scheduled Pill Counts) at Week 4

Time frame: Study week 4 (4 weeks after study medication start)

Participants' adherence to furosemide will be assessed at scheduled pill counts conducted by the study team at study week 4. Participants' adherence to furosemide will be defined <20% pills remaining at the scheduled pill counts. The percentage of participants who are adherent to furosemide will be determined.
Percentage of Participants Who Are Adherent to Furosemide (<20% Pills Remaining at Scheduled Pill Counts) at Week 5

Time frame: Study week 5 (5 weeks after study medication start)

Participants' adherence to furosemide will be assessed at scheduled pill counts conducted by the study team at study week 5. Participants' adherence to furosemide will be defined <20% pills remaining at the scheduled pill counts. The percentage of participants who are adherent to furosemide will be determined.
Percentage of Participants Who Are Adherent to Furosemide (<20% Pills Remaining at Scheduled Pill Counts) at Week 6

Time frame: Study week 6 (6 weeks after study medication start)

Participants' adherence to furosemide will be assessed at scheduled pill counts conducted by the study team at study week 6. Participants' adherence to furosemide will be defined <20% pills remaining at the scheduled pill counts. The percentage of participants who are adherent to furosemide will be determined.
Percentage of Participants Who Are Adherent to Furosemide (<20% Pills Remaining at Scheduled Pill Counts) at Week 8

Time frame: Study week 8 (8 weeks after study medication start)

Participants' adherence to furosemide will be assessed at scheduled pill counts conducted by the study team at study week 8. Participants' adherence to furosemide will be defined <20% pills remaining at the scheduled pill counts. The percentage of participants who are adherent to furosemide will be determined.
Percentage of Participants Who Are Adherent to Furosemide (<20% Pills Remaining at Scheduled Pill Counts) at Week 10

Time frame: Study week 10 (10 weeks after study medication start)

Participants' adherence to furosemide will be assessed at scheduled pill counts conducted by the study team at study week 10. Participants' adherence to furosemide will be defined <20% pills remaining at the scheduled pill counts. The percentage of participants who are adherent to furosemide will be determined.
Percentage of Participants Who Are Adherent to Furosemide (<20% Pills Remaining at Scheduled Pill Counts) at Week 12

Time frame: Study week 12 (12 weeks after study medication start)

Participants' adherence to furosemide will be assessed at scheduled pill counts conducted by the study team at study week 12. Participants' adherence to furosemide will be defined <20% pills remaining at the scheduled pill counts. The percentage of participants who are adherent to furosemide will be determined.
Percentage of Participants Who Are Adherent to Furosemide (<20% Pills Remaining at Scheduled Pill Counts) at Week 14

Time frame: Study week 14 (14 weeks after study medication start)

Participants' adherence to furosemide will be assessed at scheduled pill counts conducted by the study team at study week 14. Participants' adherence to furosemide will be defined <20% pills remaining at the scheduled pill counts. The percentage of participants who are adherent to furosemide will be determined.
Percentage of Participants Who Are Adherent to Furosemide (<20% Pills Remaining at Scheduled Pill Counts) at Week 16

Time frame: Study week 16 (16 weeks after study medication start)

Participants' adherence to furosemide will be assessed at scheduled pill counts conducted by the study team at study week 16. Participants' adherence to furosemide will be defined <20% pills remaining at the scheduled pill counts. The percentage of participants who are adherent to furosemide will be determined.
Percentage of Participants Who Are Adherent to Furosemide (<20% Pills Remaining at Scheduled Pill Counts) at Week 18

Time frame: Study week 18 (18 weeks after study medication start)

Participants' adherence to furosemide will be assessed at scheduled pill counts conducted by the study team at study week 18. Participants' adherence to furosemide will be defined <20% pills remaining at the scheduled pill counts. The percentage of participants who are adherent to furosemide will be determined.
Percentage of Participants Who Are Adherent to Furosemide (<20% Pills Remaining at Scheduled Pill Counts) at Week 19

Time frame: Study week 19 (19 weeks after study medication start)

Participants' adherence to furosemide will be assessed at scheduled pill counts conducted by the study team at study week 19. Participants' adherence to furosemide will be defined <20% pills remaining at the scheduled pill counts. The percentage of participants who are adherent to furosemide will be determined.

Sponsors and collaborators

Lead sponsor

University of North Carolina, Chapel Hill

Other

Collaborators

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Registry information

Important dates

Study start: 2020
Primary completion: 2021
Study completion: 2021
First posted: Nov 10, 2020
Registry last updated: Jun 13, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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Key information

Conditions

Age range

Sex eligibility

Study type

Phase

Primary location

Who can participate

Treatment and study plan

Furosemide (loop diuretic) Tablets

Primary outcomes

Percentage of Participants Who Have a Defined Increase in 24-hour Urine Volume From Baseline to Week 5

Percentage of Participants Who Have a Defined Increase in 24-hour Urine Volume From Baseline to Week 12

Percentage of Participants Who Have a Defined Increase in 24-hour Urine Volume From Baseline to Week 18

Percentage of Participants With A Serum Potassium <3.2 mEq/L at Week 1

Percentage of Participants With a Serum Potassium <3.2 mEq/L at Week 2

Percentage of Participants With a Serum Potassium <3.2 mEq/L at Week 3

Percentage of Participants With a Serum Potassium <3.2 mEq/L at Week 4

Percentage of Participants With a Serum Potassium <3.2 mEq/L at Week 5

Percentage of Participants With a Serum Potassium <3.2 mEq/L at Week 6

Percentage of Participants With a Serum Potassium <3.2 mEq/L at Week 9

Percentage of Participants With a Serum Potassium <3.2 mEq/L at Week 13

Percentage of Participants With a Serum Potassium <3.2 mEq/L at Week 17

Percentage of Participants With a Serum Magnesium <0.8 mEq/L at Week 1

Percentage of Participants With a Serum Magnesium <0.8 mEq/L at Week 2

Percentage of Participants With a Serum Magnesium <0.8 mEq/L at Week 3

Percentage of Participants With a Serum Magnesium <0.8 mEq/L at Week 4

Percentage of Participants With a Serum Magnesium <0.8 mEq/L at Week 5

Percentage of Participants With a Serum Magnesium <0.8 mEq/L at Week 6

Percentage of Participants With a Serum Magnesium <0.8 mEq/L at Week 9

Percentage of Participants With a Serum Magnesium <0.8 mEq/L at Week 13

Percentage of Participants With a Serum Magnesium <0.8 mEq/L at Week 17

Percentage of Participants With a Serum Corrected Calcium <7.0 mg/dL at Week 1

Percentage of Participants With a Serum Corrected Calcium <7.0 mg/dL at Week 2

Percentage of Participants With a Serum Corrected Calcium <7.0 mg/dL at Week 3

Percentage of Participants With a Serum Corrected Calcium <7.0 mg/dL at Week 4

Percentage of Participants With a Serum Corrected Calcium <7.0 mg/dL at Week 5

Percentage of Participants With a Serum Corrected Calcium <7.0 mg/dL at Week 6

Percentage of Participants With a Serum Corrected Calcium <7.0 mg/dL at Week 9

Percentage of Participants With a Serum Corrected Calcium <7.0 mg/dL at Week 13

Percentage of Participants With a Serum Corrected Calcium <7.0 mg/dL at Week 17

Percentage of Participants With a Serum Furosemide Level >12 Micrograms/L at Week 1.

Percentage of Participants With a Serum Furosemide Level >12 Micrograms/L at Week 2.

Percentage of Participants With a Serum Furosemide Level >12 Micrograms/L at Week 3.

Percentage of Participants With a Serum Furosemide Level >12 Micrograms/L at Week 4.

Percentage of Participants With a Serum Furosemide Level >12 Micrograms/L at Week 5.

Percentage of Participants With a Serum Furosemide Level >12 Micrograms/L at Week 6.

Percentage of Participants With a Serum Furosemide Level >12 Micrograms/L at Week 9.

Percentage of Participants With a Serum Furosemide Level >12 Micrograms/L at Week 13.

Percentage of Participants With a Serum Furosemide Level >12 Micrograms/L at Week 17.

Percentage of Participants That Experience Dialysis-associated Hypotension up to Week 1

Percentage of Participants That Experience Dialysis-associated Hypotension up to Week 2

Percentage of Participants That Experience Dialysis-associated Hypotension up to Week 3

Percentage of Participants That Experience Dialysis-associated Hypotension up to Week 4

Percentage of Participants That Experience Dialysis-associated Hypotension up to Week 5

Percentage of Participants That Experience Dialysis-associated Hypotension up to Week 6

Percentage of Participants That Experience Dialysis-associated Hypotension up to Week 7

Percentage of Participants That Experience Dialysis-associated Hypotension up to Week 8

Percentage of Participants That Experience Dialysis-associated Hypotension up to Week 9

Percentage of Participants That Experience Dialysis-associated Hypotension up to Week 10

Percentage of Participants That Experience Dialysis-associated Hypotension up to Week 11

Percentage of Participants That Experience Dialysis-associated Hypotension up to Week 12

Percentage of Participants That Experience Dialysis-associated Hypotension up to Week 13

Percentage of Participants That Experience Dialysis-associated Hypotension up to Week 14

Percentage of Participants That Experience Dialysis-associated Hypotension up to Week 15

Percentage of Participants That Experience Dialysis-associated Hypotension up to Week 16

Percentage of Participants That Experience Dialysis-associated Hypotension up to Week 17

Percentage of Participants That Experience Dialysis-associated Hypotension up to Week 18

Percentage of Participants Reporting a Severe or Very Severe Rash Attributable to Furosemide at Week 1

Percentage of Participants Reporting a Severe or Very Severe Rash Attributable to Furosemide at Week 2

Percentage of Participants Reporting a Severe or Very Severe Rash Attributable to Furosemide at Week 3

Percentage of Participants Reporting a Severe or Very Severe Rash Attributable to Furosemide at Week 4

Percentage of Participants Reporting a Severe or Very Severe Rash Attributable to Furosemide at Week 5

Percentage of Participants Reporting a Severe or Very Severe Rash Attributable to Furosemide at Week 6

Percentage of Participants Reporting a Severe or Very Severe Rash Attributable to Furosemide at Week 8

Percentage of Participants Reporting a Severe or Very Severe Rash Attributable to Furosemide at Week 10

Percentage of Participants Reporting a Severe or Very Severe Rash Attributable to Furosemide at Week 12

Percentage of Participants Reporting a Severe or Very Severe Rash Attributable to Furosemide at Week 14

Percentage of Participants Reporting a Severe or Very Severe Rash Attributable to Furosemide at Week 16

Percentage of Participants Reporting a Severe or Very Severe Rash Attributable to Furosemide at Week 18