Abstract
KEY POINTS: This phase 2 trial assessed baxdrostat, an aldosterone synthase inhibitor, in participants with CKD and uncontrolled hypertension. Baxdrostat showed placebo-corrected reduction in systolic BP of –8.1 (95% confidence interval, –13.4 to –2.8) mm Hg, P = 0.003. Baxdrostat was well tolerated; hyperkalemia was the most frequent treatment-emergent adverse event. BACKGROUND: Aldosterone increases BP and contributes to CKD progression. We evaluated the efficacy and safety of baxdrostat, an aldosterone synthase inhibitor, in participants with CKD and uncontrolled hypertension. METHODS: This was a phase 2, randomized, double-blind, placebo-controlled, multicenter trial (NCT05432167). Eligible participants were treated with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker and had a mean seated office systolic BP ≥140 mm Hg (without diabetes) or ≥130 mm Hg (with type 2 diabetes) and a urine albumin-creatinine ratio of≥100 mg/g. Participants were randomized (1:1:1) to baxdrostat low-dose (0.5 mg up-titrated to 1 mg), high-dose (2 mg up-titrated to 4 mg), or placebo for 26 weeks. The primary end point was change from baseline in mean seated office systolic BP at week 26 in the baxdrostat pooled treatment group versus placebo. The secondary end point assessed this change by high-dose or low-dose baxdrostat; end points were tested sequentially in a hierarchal manner. RESULTS: Between April 29, 2022, and May 2, 2024, 195 participants were randomized. The mean (SD) age was 66 (11) years, 32% were women, 113 (58%) were White, and 80% had type 2 diabetes. The mean (SD) baseline systolic BP was 151.2 (13.1) mm Hg; the mean (SD) baseline eGFR was 44 (14) ml/min per 1.73 m(2), and the median (Q1, Q3) urine albumin-creatinine ratio was 714 (307, 1429) mg/g. The mean placebo-corrected change in systolic BP from baseline to week 26 for the baxdrostat pooled group was –8.1 (95% confidence interval, −13.4 to −2.8; P = 0.003) mm Hg; low-dose −9.0 (−15.1 to −2.9; P = 0.004) mm Hg; high-dose −7.2 (−13.2 to −1.2; P = 0.02) mm Hg. Hyperkalemia was recorded as an adverse event in 41% (53/128) of participants in the baxdrostat pooled group and 5% (3/64) in the placebo group. CONCLUSIONS: Baxdrostat reduced systolic BP in participants with CKD and uncontrolled hypertension. Hyperkalemia was reported more commonly as an adverse event with baxdrostat versus placebo. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: NCT05432167.