Related Experiment Video
Updated: Dec 15, 2025
5/6th Nephrectomy in Combination with High Salt Diet and Nitric Oxide Synthase Inhibition to Induce Chronic Kidney Disease in the Lewis Rat
Published on: July 3, 2013
Design and Baseline Characteristics of the Chlorthalidone in Chronic Kidney Disease (CLICK) Trial
Rajiv Agarwal1, Andrew E Cramer2, Mary Balmes-Fenwick2
1Division of Nephrology, Department of Medicine, Indiana University School of Medicine and Richard L. Roudebush Veterans Administration Medical Center, Indianapolis, Indiana, USA, ragarwal@iu.edu.
Insights
Chlorthalidone (CTD) is being studied for its effectiveness in managing hypertension in advanced chronic kidney disease (CKD) patients. The CLICK trial investigates CTD
Area of Science:
- Nephrology
- Cardiology
- Clinical Pharmacology
Background:
- Hypertension is a common comorbidity in chronic kidney disease (CKD).
- Diuretics are standard for blood pressure (BP) management.
- Limited data exist on chlorthalidone (CTD) use in advanced CKD hypertension.
Purpose of the Study:
- To evaluate the efficacy and safety of CTD in patients with stage 4 CKD and uncontrolled hypertension.
- To determine if CTD improves BP control by reducing extracellular fluid volume.
- To assess CTD's potential for target organ protection in this population.
Main Methods:
- Phase II, double-blind, randomized controlled trial (CLICK study).
- 131 patients with stage 4 CKD and hypertension randomized to placebo or CTD.
- 12-week double-blind treatment phase with dose escalation for CTD.
Main Results:
- Average patient age 65.8 years, 79% male, 79% with diabetes.
- Mean eGFR 23.2 mL/min/1.73 m2; high baseline BP (141.7/73.8 mm Hg).
- 60% of patients were on loop diuretics prior to randomization.
Conclusions:
- The CLICK study aims to determine CTD's safety and effectiveness in stage 4 CKD patients.
- Results will inform clinical practice regarding diuretic choice in advanced CKD.
Background:
Hypertension often accompanies chronic kidney disease (CKD), and diuretics are widely prescribed to reduce blood pressure (BP). Chlorthalidone (CTD) is a thiazide-like diuretic and an effective antihypertensive drug, yet little data exist to support its use in treating hypertension in individuals with advanced CKD.
Methods:
Chlorthalidone in Chronic Kidney Disease (CLICK) is a phase II, single-institution, multicenter, double-blind randomized control trial to test the hypothesis that CTD improves BP, through reduction of extracellular fluid volume, and results in target organ protection in patients with stage 4 CKD and poorly controlled hypertension. After a single-blind placebo run-in for 2 weeks and confirmation of hypertension by 24-h ambulatory blood pressure (ABP), patients are randomized to either placebo or CTD 12.5 mg once daily (QD) followed by dose escalation. Randomization is stratified by prior loop diuretic use, and the double-blind phase lasts 12 weeks. With a total of 160 patients, the study will have ≥80% power to detect a 6 mm Hg difference in systolic 24-h ABP between the 2 treatment groups.
Results:
Between June 2016 and October 2019, 131 patients have been randomized. The baseline characteristics are as follows: average age 65.8 years, 79% men, 36% Black, 79% with diabetes, mean eGFR 23.2 mL/min/1.73 m2, median urine albumin/creatinine ratio 923 mg/g, average number of BP medications 3.4, 60% on loop diuretics, and 24-h ABP averaged 141.7/73.8 mm Hg.
Conclusion:
Among patients with stage 4 CKD and uncontrolled hypertension, CLICK should answer the question whether CTD is safe and effective.
Related Concept Videos
01:25Chronic Kidney Disease I: Introduction
01:18Chronic Kidney Disease IV: Nursing Management
01:24Chronic Kidney Disease II: Clinical Manifestations
01:28Chronic Kidney Disease III: Interprofessional Care
01:25Drug Dosing in Renal Diseases: Dose Adjustments Based on Drug Clearance and Elimination Rate Constant
01:15Antihypertensive Drugs: Thiazide-Class Diuretics