Effect of KBP-5074 on Blood Pressure in Advanced Chronic Kidney Disease: Results of the BLOCK-CKD Study

Abstract

In patients with resistant or poorly controlled hypertension and advanced chronic kidney disease, mineralocorticoid receptor antagonists are recommended; however, hyperkalemia limits their use. BLOCK-CKD was a phase 2b, multicenter, randomized, double-blind, placebo-controlled, parallel-group study that evaluated the safety, efficacy, and pharmacokinetics of KBP-5074, a nonsteroidal mineralocorticoid receptor antagonist, for uncontrolled hypertension in patients with stage 3b/4 chronic kidney disease. The study tested the hypothesis that addition of KBP-5074 to standard treatment lowers blood pressure without increased risk of hyperkalemia. Patients (N=162) were randomly assigned 1:1:1 to once-daily oral treatment with placebo, KBP-5074 0.25 mg, or KBP-5074 0.5 mg. The primary end point was systolic blood pressure change from baseline at day 84. Baseline mean (SD) systolic blood pressure was 155.3 (13.55) mm Hg. After 84 days, the placebo-subtracted treatment mean difference (SE) was −7.0 (3.37) mm Hg with KBP-5074 0.25 mg ( P =0.0399) and −10.2 (3.32) mm Hg with KBP-5074 0.5 mg ( P =0.0026). Hyperkalemia incidence, ≥5.6 <6 mmol/L, were similar among groups 5 (8.8%) placebo, 6 (11.8%) 0.25 mg, and 9 (16.7%) 0.5 mg patients. No hyperkalemia ≥6.0 mmol/L was observed. We conclude that KBP-5074 effectively lowers blood pressure with some risk of hyperkalemia in individuals with advanced chronic kidney disease and uncontrolled blood pressure. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03574363.