Effect of baxdrostat on ambulatory blood pressure in patients with resistant hypertension (Bax24): a phase 3, randomised, double-blind, placebo-controlled trial.

We aimed to assess the effect of baxdrostat, a selective aldosterone synthase inhibitor, on ambulatory blood pressure in patients with resistant hypertension.

我们的目标是评估选择性醛固酮合酶抑制剂baxdrostat对难治性高血压患者动态血压的影响。

Methods

The Bax24 international, phase 3, randomised, double-blind, placebo-controlledtrial recruited adults (aged ≥18 years) with seated systolic blood pressure (SBP) ≥140 mm Hg and <170 mm Hg, despite receiving three or more antihypertensive medications, including a diuretic, from 79 clinical sites (primary, secondary, and tertiary centres, in addition to research centres) in 22 countries.

Bax24国际第三阶段随机双盲安慰剂对照试验招募了年龄≥18岁的成年人，这些人的坐位收缩压（SBP）≥140毫米汞柱且<170毫米汞柱，尽管已经接受了包括利尿剂在内的三种或更多种降压药物治疗，从22个国家的79个临床站点（包括初级、二级和三级中心以及研究中心）招募。

Following a 2-week placebo run-in period, patients with 24 h ambulatory SBP ≥130 mm Hg were randomly assigned (1:1) to receive 2 mg baxdrostat or placebo orally once daily for 12 weeks, in addition to background therapy (stratified by baseline ambulatory SBP <140 mm Hg or ≥140 mm Hg).

经过2周的安慰剂导入期后，24小时动态收缩压≥130毫米汞柱的患者被随机分配（1:1），每天一次口服2毫克的baxdrostat或安慰剂，为期12周，除了背景治疗（根据基线动态收缩压<140毫米汞柱或≥140毫米汞柱进行分层）。

Investigators, patients, and trial staff were masked to treatment assignment.

研究者、患者和试验工作人员对治疗分配情况进行了盲法处理。

The primary endpoint was change in 24 h ambulatory SBP from baseline to week 12, assessed by analysis of covariance in patients administered at least one dose of study medication with valid ambulatory SBP measurement at baseline and week 12.

主要终点是基线至第12周24小时动态收缩压（SBP）的变化，通过协方差分析评估至少接受一次研究药物剂量且在基线和第12周具有有效动态收缩压测量的患者。

Missing or invalid ambulatory SBP measurements were not imputed.

未记录或无效的动态血压测量值未进行估算。

The safety analysis included all patients who received at least one dose of study medication.

安全性分析包括了所有至少接受了一剂研究药物的患者。

This trial is registered with ClinicalTrials.gov, NCT06168409, and is complete.

该试验已在ClinicalTrials.gov注册，编号为NCT06168409，并已完成。

Results

Between March 1, 2024, and April 16, 2025, 854 patients were screened, 636 were excluded (437 before the placebo run-in and 199 during the placebo run-in) and 217 were randomly assigned to and received baxdrostat (n=108) or placebo (n=109). 140 patients (65%) were male, 77 (35%) patients were female, and 170 patients (78%) were White.

在2024年3月1日至2025年4月16日期间，共有854名患者接受了筛查，其中636名患者被排除在外（437名在安慰剂启动前被排除，199名在安慰剂启动期间被排除），217名患者被随机分配并接受了baxdrostat（n=108）或安慰剂（n=109）。其中140名患者（65%）为男性，77名患者（35%）为女性，170名患者（78%）为白人。

The median age was 60·0 years (IQR 51·0-68·0).

中位年龄为60·0岁（四分位数间距51·0-68·0）。

At 12 weeks, the change from baseline in the least-squares mean 24 h ambulatory SBP was -16·6 mm Hg (95% CI -18·8 to -14·3) in the baxdrostat group (n=89) and -2·6 mm Hg (-4·7 to -0·4) in the placebo group (n=95); the estimated placebo-corrected difference was -14·0 mm Hg (-17·2 to -10·8; p<0·0001).

在12周时，从基线开始的最小二乘平均24小时动态收缩压变化为baxdrostat组（n=89）的-16·6毫米汞柱（95%置信区间-18·8至-14·3毫米汞柱），安慰剂组（n=95）的-2·6毫米汞柱（-4·7至-0·4毫米汞柱）；估计的安慰剂校正差异为-14·0毫米汞柱（-17·2至-10·8毫米汞柱；p<0·0001）。

Adverse events occurred in 56 (52%) of 108 patients in the baxdrostat group and 40 (37%) of 109 patients in the placebo group.

在接受baxdrostat治疗的108名患者中，有56名（52%）出现了不良事件，而在接受安慰剂治疗的109名患者中，有40名（37%）出现了不良事件。

A confirmed potassium level of more than 6 mmol/L occurred in three (3%) of the 108 baxdrostat recipients and in none of the placebo recipients.

在接受baxdrostat治疗的108名患者中，有三名（3%）出现了确认的钾水平超过6毫摩尔/升，而在安慰剂接受者中没有出现这种情况。

interpretation

Baxdrostat significantly reduced 24 h ambulatory SBP versus placebo in patients with resistant hypertension, providing further evidence of the potential of aldosterone synthase inhibition for treatment of hard-to-control hypertension.

Baxdrostat 显著降低了难治性高血压患者的24小时动态收缩压（SBP），与安慰剂相比，为醛固酮合酶抑制治疗难控制性高血压提供了进一步的证据。

funding

AstraZeneca.

阿斯利康。