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Kidney Week

Abstract: FR-OR68

Chlorthalidone for Hypertension in Advanced CKD (CLICK): A Randomized Double-Blind Trial

Session Information

Category: CKD (Non-Dialysis)

  • 2102 CKD (Non-Dialysis): Clinical, Outcomes, and Trials

Authors

  • Agarwal, Rajiv, Indiana University School of Medicine, Indianapolis, Indiana, United States
  • Sinha, Arjun D., Indiana University School of Medicine, Indianapolis, Indiana, United States
  • Cramer, Andrew E., Indiana University School of Medicine, Indianapolis, Indiana, United States
  • Balmes-Fenwick, Mary, Indiana University School of Medicine, Indianapolis, Indiana, United States
  • Dickinson, Jazmyn H., Indiana University School of Medicine, Indianapolis, Indiana, United States
  • Ouyang, Fangqian, Indiana University School of Medicine, Indianapolis, Indiana, United States
  • Tu, Wanzhu, Indiana University School of Medicine, Indianapolis, Indiana, United States
Background


Hypertension, a common risk factor for both cardiovascular disease and chronic kidney disease (CKD), remains poorly controlled, especially among patients with advanced CKD.

Methods

The chlorthalidone (CTD) in chronic kidney disease (CLICK) study was a placebo-controlled, double-blind, randomized control trial of CTD versus placebo in patients with advanced CKD. Here, patients with stage 4 CKD and poorly controlled hypertension as confirmed by 24-hour ambulatory BP monitoring were randomly assigned to either placebo or CTD 12.5 mg daily in a 1:1 ratio stratified by prior loop diuretic use. The primary end point was the change in 24-hour systolic ambulatory BP from baseline to 12 weeks and was multiply imputed for missing data. Secondary outcome measures were the change from baseline to 12 weeks in the following measures: urine albumin to urine creatinine ratio, NT-pro BNP, plasma renin, plasma aldosterone, and total body volume. Long term follow up was planned for 3 years. An NHLBI-appointed DSMB had trial oversight.

Results

Of the 160 randomized,140 patients (88%) completed the 12 weeks of double-blind exposure phase.

Mean 24-hour ambulatory BP at randomization was 140.1 (8.1)/72.8(9.3) mmHg in the placebo group and 142.6 (8.1)/74.6 (10.1) mmHg in the CTD group. The adjusted change from baseline to 12 weeks in 24-hour systolic blood pressure was -0.5 (95% CI, -3.5 to 2.5) mmHg in the placebo group and -11.0 (95% CI, -13.9 to -8.1) mmHg in the CTD group. The between group difference was -10.5 (95% CI, -14.6 to -6.4: p<0.0001) mmHg.

Compared to placebo, the urine albumin to urine creatinine ratio in the CTD group at 12 weeks was 50% lower (95% CI, 37% to 60%). CTD also induced changes in NT-proBNP, renin, aldosterone and total body volume were directionally consistent with a diuretic effect. Following randomization, hypokalemia, reversible increases in serum creatinine, hyperglycemia, dizziness, and hyperuricemia occurred more frequently in the CTD group.

Conclusion

In summary, this trial showed that treatment with CTD could effectively treat poorly controlled systolic hypertension in patients with advanced CKD. The reduction in albuminuria points to an early effect of target organ protection.

(funded by National Institutes of Health NHLBI R01 HL126903 ; registration number NCT02841280)

Funding

  • Other NIH Support