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Chlorthalidone in Chronic Kidney Disease (CLICK)

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ClinicalTrials.gov Identifier: NCT02841280
Recruitment Status : Recruiting
First Posted : July 22, 2016
Last Update Posted : January 24, 2019
Sponsor:
Information provided by (Responsible Party):
Rajiv Agarwal, Indiana University

Tracking Information
First Submitted Date  ICMJE May 27, 2016
First Posted Date  ICMJE July 22, 2016
Last Update Posted Date January 24, 2019
Study Start Date  ICMJE July 2016
Estimated Primary Completion Date January 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 19, 2016)
Change from baseline to 12 weeks in systolic ambulatory blood pressure in the chlorthalidone group compared to placebo. [ Time Frame: Baseline to 12 weeks ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02841280 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 19, 2016)
  • Changes in albuminuria from baseline at each 4 week visit in the log transformed albumin/creatinine ratio in the chlorthalidone group compared to placebo, as measured by overnight urine collection. [ Time Frame: Baseline to 12 weeks ]
  • Change from baseline at each 4 week visit in log of aldosterone to renin ratio in the chlorthalidone group compared to placebo. No adjustments will be made for multiple comparisons. [ Time Frame: Baseline to 12 weeks ]
  • Change from baseline at each 4 week visit in log of B-type natriuretic peptide in the chlorthalidone group compared to placebo. No adjustments will be made for multiple comparisons. [ Time Frame: Baseline to 12 weeks ]
  • 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 ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Outcome Measures  ICMJE Not Provided
Original Other Outcome Measures  ICMJE Not Provided
 
Descriptive Information
Brief Title  ICMJE Chlorthalidone in Chronic Kidney Disease
Official Title  ICMJE Not Provided
Brief Summary 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.
Detailed Description This is a two-center, placebo-controlled, double-blind, randomized controlled trial of chlorthalidone (CTD) in patients with CKD and poorly controlled hypertension
Study Type  ICMJE Interventional
Study Phase Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Renal Insufficiency, Chronic
  • Hypertension
Intervention  ICMJE
  • Drug: Chlorthalidone
    This is a forced-titration study and the study drug or placebo will be increased if goal BP is not achieved (dosage of chlorthalidone not to exceed 50 mg)
  • Drug: Placebo
    This is a forced-titration study and the study drug or placebo will be increased if goal BP is not achieved (dosage of chlorthalidone not to exceed 50 mg)
Study Arms
  • Experimental: Chlorthalidone
    Subjects with stage 4 chronic kidney disease (CKD) and poorly controlled hypertension confirmed by 24 hour ambulatory blood pressure monitoring will be randomized into two groups, one receiving placebo and one receiving a diuretic called chlorthalidone (12.5 mg at randomization). Doubling of the dose of the diuretic (up to 50 mg) or placebo will occur every 4 weeks if required by home blood pressure (BP) results.
    Intervention: Drug: Chlorthalidone
  • Placebo Comparator: Placebo
    Subjects with stage 4 CKD and poorly controlled hypertension confirmed by 24 hour ambulatory blood pressure monitoring will be randomized into two groups, one receiving placebo and one receiving a diuretic called chlorthalidone (12.5 mg at randomization). Doubling of the dose of the diuretic (up to 50 mg) or placebo will occur every 4 weeks if required by home BP results.
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 19, 2016)
160
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date January 2022
Estimated Primary Completion Date January 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Age greater than 18 years.
  2. 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.
  3. Hypertension. This is defined as BP of either ≥130 systolic or ≥80 mmHg by 24-hour ambulatory BP monitoring.
  4. 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:

  1. Use of thiazide or thiazide-like drugs in the previous 12 weeks.
  2. Use of furosemide in a dose >200 mg/d.
  3. BP of either ≥160 systolic or ≥100 mmHg by 24-hour ambulatory BP monitoring.
  4. Expected to receive renal replacement therapy within the next 3 months.
  5. Myocardial infarction, heart failure hospitalization, or stroke ≤3 months prior to randomization.
  6. 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).
  7. Known hypersensitivity to thiazide or sulfa drugs.
  8. Organ transplant recipient or therapy with immunosuppressive agents.
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts  ICMJE
Contact: Rajiv Agarwal, MD 317-988-2241 ragarwal@iu.edu
Contact: William B Rogers, BS 317-988-3024 rogersbe@iu.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02841280
Other Study ID Numbers  ICMJE 1507540384
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement Not Provided
Responsible Party Rajiv Agarwal, Indiana University
Study Sponsor  ICMJE Indiana University
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Rajiv Agarwal, MD Indiana University
PRS Account Indiana University
Verification Date January 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP