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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 : August 22, 2017
Sponsor:
Information provided by (Responsible Party):
Rajiv Agarwal, Indiana University

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.

Condition or disease Intervention/treatment Phase
Renal Insufficiency, Chronic Hypertension Drug: Chlorthalidone Drug: Placebo Phase 2

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 : Interventional  (Clinical Trial)
Estimated Enrollment : 160 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Study Start Date : July 2016
Estimated Primary Completion Date : January 2021
Estimated Study Completion Date : January 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Kidney Diseases

Arm Intervention/treatment
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.
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)

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.
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)




Primary Outcome Measures :
  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 Outcome Measures :
  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, as measured by overnight urine collection. [ Time Frame: Baseline to 12 weeks ]
  2. 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 ]
  3. 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 ]
  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 ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02841280


Contacts
Contact: Rajiv Agarwal, MD 317-988-2241 ragarwal@iu.edu
Contact: William B Rogers, BS 317-988-3024 rogersbe@iu.edu

Locations
United States, Indiana
Indiana University School of Medicine, Division of Nephrology Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Rajiv Agarwal, MD    317-988-2241    ragarwal@iu.edu   
Contact: William Rogers, BS    317-988-3024    rogersbe@iu.edu   
Principal Investigator: Rajiv Agarwal, MD         
Sponsors and Collaborators
Indiana University
Investigators
Principal Investigator: Rajiv Agarwal, MD Indiana University

Responsible Party: Rajiv Agarwal, Professor of Medicine, Indiana University
ClinicalTrials.gov Identifier: NCT02841280     History of Changes
Other Study ID Numbers: 1507540384
First Posted: July 22, 2016    Key Record Dates
Last Update Posted: August 22, 2017
Last Verified: August 2017

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

Additional relevant MeSH terms:
Renal Insufficiency, Chronic
Renal Insufficiency
Kidney Diseases
Urologic Diseases
Chlorthalidone
Antihypertensive Agents
Diuretics
Natriuretic Agents
Physiological Effects of Drugs
Sodium Chloride Symporter Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action