Rajiv Agarwal1, Andrew E Cramer2, Mary Balmes-Fenwick2, Arjun D Sinha2, Fangqian Ouyang3, Wanzhu Tu3. 1. Division of Nephrology, Department of Medicine, Indiana University School of Medicine and Richard L. Roudebush Veterans Administration Medical Center, Indianapolis, Indiana, USA, ragarwal@iu.edu. 2. Division of Nephrology, Department of Medicine, Indiana University School of Medicine and Richard L. Roudebush Veterans Administration Medical Center, Indianapolis, Indiana, USA. 3. Department of Biostatistics, Richard M. Fairbanks School of Public Health, Indiana University School of Medicine, Indianapolis, Indiana, USA.
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-hABP 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, and24-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.
RCT Entities:
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.
Authors: O Ortiz; M Russell; T L Daley; R N Baumgartner; M Waki; S Lichtman; J Wang; R N Pierson; S B Heymsfield Journal: Am J Clin Nutr Date: 1992-01 Impact factor: 7.045
Authors: Michael E Ernst; Barry L Carter; Chris J Goerdt; Jennifer J G Steffensmeier; Beth Bryles Phillips; M Bridget Zimmerman; George R Bergus Journal: Hypertension Date: 2006-01-23 Impact factor: 10.190
Authors: Paul A James; Suzanne Oparil; Barry L Carter; William C Cushman; Cheryl Dennison-Himmelfarb; Joel Handler; Daniel T Lackland; Michael L LeFevre; Thomas D MacKenzie; Olugbenga Ogedegbe; Sidney C Smith; Laura P Svetkey; Sandra J Taler; Raymond R Townsend; Jackson T Wright; Andrew S Narva; Eduardo Ortiz Journal: JAMA Date: 2014-02-05 Impact factor: 56.272
Authors: Javed Butler; Daniel E Forman; William T Abraham; Stephen S Gottlieb; Evan Loh; Barry M Massie; Christopher M O'Connor; Michael W Rich; Lynne Warner Stevenson; Yongfei Wang; James B Young; Harlan M Krumholz Journal: Am Heart J Date: 2004-02 Impact factor: 4.749
Authors: Laura C Plantinga; Edgar R Miller; Lesley A Stevens; Rajiv Saran; Kassandra Messer; Nicole Flowers; Linda Geiss; Neil R Powe Journal: Hypertension Date: 2009-05-26 Impact factor: 10.190
Authors: Ron T Gansevoort; Ricardo Correa-Rotter; Brenda R Hemmelgarn; Tazeen H Jafar; Hiddo J Lambers Heerspink; Johannes F Mann; Kunihiro Matsushita; Chi Pang Wen Journal: Lancet Date: 2013-05-31 Impact factor: 79.321
Authors: Rajiv Agarwal; Arjun D Sinha; Andrew E Cramer; Mary Balmes-Fenwick; Jazmyn H Dickinson; Fangqian Ouyang; Wanzhu Tu Journal: N Engl J Med Date: 2021-11-05 Impact factor: 176.079