Design and Baseline Characteristics of the Chlorthalidone in Chronic Kidney Disease (CLICK) Trial

Abstract

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.