Abstract Body (Do not enter title and authors here): Hypothesis and Purpose: Baxdrostat is a highly selective aldosterone synthase inhibitor that reduced seated office systolic blood pressure (sOSBP) in patients with resistant hypertension (rHTN) in a phase 2 trial, despite a large placebo effect. Guidelines recommend ambulatory blood pressure (BP) monitoring (ABPM) for patients with rHTN to exclude pseudo-rHTN. This phase 3 Bax24 trial was designed to evaluate the effect of baxdrostat on 24-hour average ambulatory SBP (24h-ASBP) in patients with rHTN confirmed by ABPM.
Study Design: Bax24 is a multinational, randomized, double-blind, placebo-controlled phase 3 trial (NCT06168409).
Sample Size: ~212.
Population Studied: Patients aged ≥18 years with apparent rHTN at screening (sOSBP ≥140 mmHg to <170 mmHg despite receiving ≥3 antihypertensive treatments, including a diuretic, at optimal doses) and 24h-ASBP ≥130 mmHg at randomization, estimated glomerular filtration rate ≥45 mL/min/1.73m², and serum potassium ≥3.5 to <5.0 mmol/L.
Interventions: After a 2-week single-blind placebo run-in period, patients with 24h-ASBP ≥130 mmHg were randomized 1:1 to baxdrostat 2 mg or placebo once daily for a 12-week double-blind period. Background antihypertensive treatments were maintained throughout. Ambulatory BP was measured every 20 minutes during daytime and every 30 minutes during nighttime at baseline and Week 12.
Power Calculations: 212 patients provided 88% statistical power to detect a treatment effect of 6 mmHg difference in change from baseline in 24h-ASBP at Week 12, assuming a standard deviation of 12 mmHg and 25% dropout rate, using a two-sample t-test (two-sided alpha level of 0.05).
Primary End Point: Change in 24h-ASBP from baseline to Week 12.
Key Secondary End Points: Change from baseline to Week 12 in: 1) nighttime/daytime ASBP; 2) 24h ambulatory diastolic BP; and 3) sOSBP.
Outcomes: Results for the primary and secondary end points, and key safety/tolerability findings, will be presented. The results will complement baxdrostat trials based on changes in sOSBP and provide further evidence of baxdrostat's BP lowering efficacy in patients with confirmed rHTN.