CLICK: Chlorthalidone effective in treatment of hypertension in patients with advanced CKD
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Chlorthalidone proved effective in the treatment of persistent hypertension in patients with advanced chronic kidney disease, according to the data presented at ASN Kidney Week.
Chlorthalidone has been approved to treat hypertension since 1961, Rajiv Agarwal, MD, MBBS, FASN, a professor of medicine at Indiana University School of Medicine, said during a press conference at the virtual meeting.
“We asked the question whether the user with a GFR less than 30 – stage 4 chronic kidney disease – who had uncontrolled hypertension could see some benefit from this drug in improving blood pressure control,” he said.
The Chlorthalidone in Chronic Kidney Disease (CLICK) study randomly assigned patients with stage 4 CKD to either a placebo or chlorthalidone group, with dosing at 12.5 mg daily. The dose was increased every 4 weeks if needed to a maximum of 50 mg per day for patients in the chlorthalidone group. Primary endpoint was the change in 24-hour systolic ambulatory blood pressure from baseline to 12 weeks, Agarwal said.
Of the 160 patients randomized for the trial, 76% had type 2 diabetes and 60% were receiving loop diuretics. Outcome measures in the secondary endpoints were the change from baseline to 12 weeks in urine albumin to urine creatinine ratio, NT-pro BNP (B-type natriuretic peptide), plasma renin, aldosterone and total body volume. Long-term follow-up was planned for 3 years, he said.
“Our baseline of mean eGFR was 23.2, and the mean number of antihypertensive drugs used by patients was 3.4,” Agarwal said at the press conference.
The mean 24-hour ambulatory blood pressure at randomization was 140.1 mm Hg for patients in the placebo group and 142.6 mm Hg for patients in the chlorthalidone group.
“The adjusted change from baseline to 12 weeks in 24-hour systolic blood pressure was -0.5 mm Hg in the placebo group and -11.0 mm Hg in the chlorthalidone group,” Agarwal said. “The between group difference was -10.5 mm Hg.”
Compared with placebo, the urine albumin-to-creatinine ratio (UACR) in the chlorthalidone group was 50% lower.
“Chlorthalidone also induced changes in NT-proBNP, renin, aldosterone and total body volume that were directionally consistent with a diuretic effect. Following randomization, hypokalemia, reversible increases in serum creatinine, hyperglycemia, dizziness and hyperuricemia occurred more frequently in the chlorthalidone group,” Agarwal said at the press conference.
In a later presentation of the data during the High-Impact Clinical Trials session, Agarwal said the CLICK trial results showed that in patients with stage 4 CKD, “chlorthalidone effectively reduces systolic blood pressure about 10 mm Hg within 4 weeks, which persists at 12 weeks, showed a reduction in UACR by 50%, suggesting kidney protection, and that blood pressure and volume contraction effects of [chlorthalidone] are long acting.”
He said chlorthalidone was “a potential low-cost solution for the treatment of hypertension” in patients with advanced CKD.
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Agarwal R, et al. Paper FR-OR68. Presented at the ASN Kidney Week; Nov. 4-7, 2021 (virtual meeting).
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