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NCT Number: NCT02841280

Chlorthalidone in Chronic Kidney Disease

It is estimated that in the United States there are approximately 8 million individuals who have moderate to severe chronic kidney disease (CKD). Among them hypertension is common and is often poorly controlled due to an expanded volume state; diuretics are frequently prescribed. Loop diuretics are potent and effective in lowering blood pressure (BP) but their use is associated with acute kidney injury. Thiazide diuretics, on the other hand, are less potent, their use may be associated with less acute kidney injury, but as yet there are no firm data to support that thiazide diuretic therapy can improve BP among subjects with advanced CKD. The investigators found 13 studies on the use of thiazide diuretics in advanced CKD either alone or in combination with loop diuretics and concluded that thiazides may be useful. Thiazides cause a negative Na balance, increase Na excretion by 10-15% and weight loss by 1-2 kg in observational studies. Observational data show that thiazides lead to an improvement in seated clinic BP of about 10-15 mmHg systolic and 5-10 mmHg diastolic whereas randomized trials show about a 15 mmHg reduction in mean BP. Randomized trials had only between 7 and 23 subjects each; accordingly, larger studies are needed to evaluate their safety and efficacy in moderate to advanced CKD.

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Key information

Conditions

Renal Insufficiency, Chronic Cardiovascular Diseases Chronic Disease Disease Attributes Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Hypertension Kidney Diseases Male Urogenital Diseases Pathologic Processes Pathological Conditions, Signs and Symptoms Renal Insufficiency Urogenital Diseases Urologic Diseases Vascular Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Indiana University School of Medicine, Division of Nephrology

Indianapolis, Indiana, 46202, United States

About this study

This is a placebo-controlled, double-blind, randomized controlled trial of chlorthalidone (CTD) in patients with CKD and poorly controlled hypertension

Who can participate

Healthy volunteers accepted: No

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

Inclusion criteria

  • Age greater than 18 years.
  • Calculated glomerular filtration rate (GFR) by 4-component Modification of Diet in Renal Disease (MDRD) formula < 30 ml/min/1.73m2 but ≥15 mL/min/1.73m2. The hospital laboratory uses isotope dilution mass spectrometry (IDMS) calibrated creatinine and the appropriate formula is used to estimate GFR.
  • Hypertension. This is defined as BP of either ≥130 systolic or ≥80 mmHg by 24-hour ambulatory BP monitoring.
  • Treatment with antihypertensive drugs: This would require the use of at least one antihypertensive drug. One of the drugs should be either an angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB). If these are contraindicated then use of a beta-blocker is required prior to randomization.

Exclusion criteria

  • Use of thiazide or thiazide-like drugs in the previous 12 weeks.
  • Use of furosemide in a dose >200 mg/d.
  • BP of either ≥160 systolic or ≥100 mmHg by 24-hour ambulatory BP monitoring.
  • Expected to receive renal replacement therapy within the next 3 months.
  • Myocardial infarction, heart failure hospitalization, or stroke ≤3 months prior to randomization.
  • Pregnant or breastfeeding women or women who are planning to become pregnant or those not using a reliable form of contraception (oral contraceptives. condoms and diaphragms will be considered reliable).
  • Known hypersensitivity to thiazide or sulfa drugs.
  • Organ transplant recipient or therapy with immunosuppressive agents.

Treatment and study plan

Chlorthalidone

Drug

This is a forced-titration study and the study drug will be increased if goal BP is not achieved (dosage of chlorthalidone not to exceed 50 mg)

Placebo

Drug

This is a forced-titration study and placebo will be increased if goal BP is not achieved.

Primary outcomes

  1. Change From Baseline to 12 Weeks in Systolic Ambulatory Blood Pressure in the Chlorthalidone Group Compared to Placebo.

    Time frame: Baseline to 12 weeks

Secondary outcomes

  1. Changes in Albuminuria From Baseline at Each 4 Week Visit in the Log Transformed Albumin/Creatinine Ratio in the Chlorthalidone Group Compared to Placebo

    Time frame: Baseline to 12 weeks

  2. Change From Baseline at Each 4 Week Visit in Log of Aldosterone and Log of Renin in the Chlorthalidone Group Compared to Placebo. No Adjustments Will be Made for Multiple Comparisons.

    Time frame: Baseline to 12 weeks

  3. Change From Baseline at Each 4 Week Visit in Log of N-terminal Pro B-type Natriuretic Peptide (NTproBNP) in the Chlorthalidone Group Compared to Placebo. No Adjustments Will be Made for Multiple Comparisons.

    Time frame: Baseline to 12 weeks

  4. Change From Baseline at Each 4 Week Visit in Body Volume in the Chlorthalidone Group Compared to Placebo. No Adjustments Will be Made for Multiple Comparisons.

    Time frame: Baseline to 12 weeks

Sponsors and collaborators

Lead sponsor

Indiana University

Other

Registry information

Acronym: CLICK

Important dates

Study start
2016
Primary completion
2021
Study completion
2021
First posted
Jul 22, 2016
Registry last updated
May 15, 2023

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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