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NCT Number: NCT04481919

Randomized Controlled Trial of urinE chemiStry Guided aCute heArt faiLure treATmEnt (ESCALATE)

This is a randomized trial of protocolized diuretic therapy guided by urinary sodium compared to structured usual care in ED patients with AHF. Participants will be recruited following an initial standard evaluation in the ED and randomized in a 1:1 fashion to structured usual care or protocolized diuretic therapy guided by urinary sodium.

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This study is active but is not currently recruiting participants.

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Key information

Age range

19 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

VA Tennessee Valley Health Service, Nashville, Tennessee, United States

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About this study

A standardized protocol driven treatment pathway for hospitalized patients started in the first few hours of ED evaluation and utilizing objective measures of diuretic response is needed. The investigators believe this would maximize diuretic efficiency, facilitate quicker resolution of congestion, avoid WHF and prolonged LOS, and reduce AHF readmissions. Propr data suggests low urine sodium predicts length of stay and outcomes after initial diuretic dosing in the outpatient and inpatient setting. Further, use of our pathway using spot urine sodium to titrate subsequent loop diuretic doses and maximize response in inpatients with AHF has shown compelling improvements in congestion and weight loss. However, a randomized trial is necessary to determine if initiating this protocol ,started in the ED, will improve AHF outcomes relative to structured usual care. Specifically, the investigators hypothesize use of spot urine sodium guided diuretic therapy will result in significant improvement in days of benefit over the 14 days after randomization. Days of benefit combines patient symptoms captured by global clinical status with clinical state quantifying the need for hospitalization and IV diuresis.

Who can participate

Healthy volunteers accepted: No

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

Inclusion criteria

  • Age > 18
  • Emergency Department diagnosis of Acute Heart Failure (AHF)
  • Any one of the following:

i. Chest radiograph or lung ultrasound consistent with AHF ii. Jugular venous distension iii. Pulmonary rales on auscultation iv. Lower extremity edema v. S3 gallop

  • > 10 pounds of volume overload physician estimate or historical dry weight
  • IV diuretic ordered or planned to be during first 24 hours of ED or inpatient stay

Exclusion criteria

  • End Stage Renal Disease (ESRD) requiring dialysis
  • Need for immediate intubation
  • Acute Coronary Syndrome - presentation consistent with myocardial ischemia AND new ST-Segment elevation/depression
  • Temperature > 100.5ºF
  • End Stage Heart Failure: transplant list or ventricular assist device
  • Concurrent use of ototoxic medications including intravenous aminoglycosides and cisplatin
  • Systolic Blood Pressure < 90 mmHg at time of consent
  • LV outflow obstruction, severe uncorrected stenotic valvular disease or severe restrictive cardiomyopathy
  • Greater than 2 doses of IV diuretic administered at the time of screening from the time of the hospital presentation leading to this admission (outside hospital time is included)
  • Severe, uncorrected serum electrolyte abnormalities at the time of consent (serum potassium <3.0 mEq/L, magnesium <1.0 mEq/L or sodium <125 or >150 mEq/l)
  • Lack of informed consent

Treatment and study plan

Protocolized diuretic therapy

Drug

The urine sodium, urine creatinine and serum creatinine results will be input into the diuretic calculator and the diuretic dose will be chosen based on daily goals for urine output and net negative fluid balance.

Primary outcomes

  1. Clinical Status Score

    Time frame: From the time of randomization through day 14

    Daily composite of the clinical state and global clinical status (GCS), expressed as an integer ranging in value from 0 (deceased) to 15 (outpatient; best possible GCS).

Secondary outcomes

  1. Inpatient clinical congestion

    Time frame: from the time of randomization through the end of protocolized IV diuretics, approximately 14 days

    Daily orthodema score

  2. Cardiorenal Death and AHF Readmission

    Time frame: within 30 days of hospital discharge

    Cardiorenal death and Acute Heart Failure Readmission

  3. Global clinical status (GCS)

    Time frame: from the time of randomization through 14 days after randomization

    measured daily using a continuous scale of 1-100

  4. Change in natriuretic peptides

    Time frame: from the time of randomization through the end of protocolized IV diuretics, approximately 14 days

    Blood measurement

  5. Net fluid loss

    Time frame: from the time of randomization through the end of protocolized IV diuretics, approximately 14 days

    difference between fluid input and urine output in ml

  6. Total urine output

    Time frame: from the time of randomization through the end of protocolized IV diuretics, approximately 14 days

    cumulative urine output in ml

  7. Weight Loss

    Time frame: from the time of randomization through the end of protocolized IV diuretics, approximately 14 days

    cumulative weight loss in pounds

  8. Home days

    Time frame: within 30 days from randomization

    Those days not in the hospital, rehab or a skilled nursing facility from the time of randomization through day 30

  9. Subclinical ototoxicity

    Time frame: at two time points: 1) the day of randomization and 2) the next calendar day after protocolized IV diuretics are stopped

    As measured by shoebox audiometry with a significant change in hearing threshold (dB) across frequencies from 250-8000 Hz

  10. Cumulative natriuresis

    Time frame: from the time of randomization through the end of protocolized diuretics, approximately 14 days

    cumulative sodium excretion estimated using the NRPE (based on spot urine creatinine and sodium)

  11. Average daily natriuresis

    Time frame: from the time of randomization through the end of protocolized diuretics, approximately 14 days

    mean daily sodium excretion estimated using the NRPE (based on spot urine creatinine and sodium)

Other outcomes

  1. Dyspnea score

    Time frame: from the time of randomization through the end of protocolized IV diuretics, approximately 14 days

    measured daily using a continuous scale from 1-100

  2. Change in Kidney injury biomarkers

    Time frame: from the time of randomization through the end of protocolized IV diuretics, approximately 14 days

    changes in the urinary tubular injury markers such as KIM-1 and NGAL

  3. Hospital Length of stay

    Time frame: from the ED presentation to hospital discharge, approximately 7 days

    number of days in the hospital

  4. 180-day all cause death

    Time frame: within 180 days of hospital discharge

    all-cause death

  5. Hypotension

    Time frame: from the time of randomization through 7 days off protocolized IV diuretics, or discharge

    Incidence of symptomatic (lightheaded, chest pain) hypotension (SBP < 80 mmHg confirmed on 2 successive measurements at least 30 minutes apart)

  6. Acute Kidney Injury Differences in Epithelial sodium channel (ENaC) levels

    Time frame: from the time of randomization through 7 days off protocolized IV diuretics, or discharge

    AKI (defined as a need for renal replacement therapy or KDIGO stage 2 or greater from a serum creatinine at randomization)

  7. Cardiorenal death or Myocardial Infarction (MI) during hospitalization

    Time frame: from the time of randomization through 7 days off protocolized IV diuretics, or discharge

    Cardiorenal death or MI as adjudicated by a clinical events committee

  8. Ototoxicity or tinnitus

    Time frame: from the time of randomization through 7 days off protocolized IV diuretics, or discharge

    Clinically significant ototoxicity or tinnitus as determined by the study team

Sponsors and collaborators

Lead sponsor

Vanderbilt University Medical Center

Other

Registry information

Official study title

A Randomized Trial of Protocolized Diuretic Therapy Compared to Standard Care in Emergency Department Patients With Acute Heart Failure

Acronym: ESCALATE

Important dates

Study start
2022
Primary completion
2025
Study completion
2026
First posted
Jul 22, 2020
Registry last updated
Jul 24, 2026

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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