PASSReviewer 1· 95% conf
The study design is rigorous: a randomized, double-blind, placebo-controlled phase 3 trial with a pre-specified power analysis, clear inclusion/exclusion criteria, and a hierarchical testing procedure to control Type I error.
Evidence
direct quote[Methods, paragraph 1]
“BaxHTN is a phase 3, multicenter, randomized, double-blind, placebo-controlled trial, described previously.”direct quote[Methods, Statistical Analyses]
“It was estimated that 720 participants would need to be randomized to achieve 98% power to detect a mean (standard deviation [SD]) difference of 6 (15) mmHg for change from baseline in seated-SBP at week 12 in favor of baxdrostat versus placebo using a two-sample t-test with a two-sided significance level of 0.025.”direct quote[Methods, paragraph 3]
“The trial enrolled men and women aged ≥18 years with either uncontrolled or resistant hypertension, defined by a mean seated-SBP ≥140 mmHg and <170 mmHg despite treatment with maximally tolerated doses of either 2 (uncontrolled hypertension) or ≥3 (resistant hypertension) antihypertensive medications of different classes, including a diuretic, for ≥4 weeks before screening.”PASSReviewer 2· 90% conf
The study design is rigorous for a phase 3 RCT: randomization is described, stratification factors are stated, power analysis is provided, and inclusion/exclusion criteria are reported. Blinding and controls (placebo) are appropriate. Some sub-criteria are not applicable for a human trial.
Evidence
direct quote[Methods, Trial Design section]
“Participants were randomly assigned 1:1:1 to receive baxdrostat 1 mg, baxdrostat 2 mg, or placebo once daily. Randomization was stratified by baseline hypertension status (uncontrolled hypertension, resistant hypertension) and baseline seated-SBP (<145, ≥145 mmHg).”direct quote[Methods, Statistical Analyses section]
“It was estimated that 720 participants would need to be randomized to achieve 98% power to detect a mean (standard deviation [SD]) difference of 6 (15) mmHg for change from baseline in seated-SBP at week 12 in favor of baxdrostat versus placebo using a two-sample t-test with a two-sided significance level of 0.025.”paraphrase[Methods, Trial Design and Statistical Analyses sections]
“Inclusion criteria: seated-SBP ≥140 and <170 mmHg despite stable treatment with 2 or ≥3 medications including a diuretic. After a placebo run-in, participants with SBP ≥135 mmHg were randomized. Exclusion criteria are referenced to the supplement. Missing data were handled by multiple imputation with a retrieved dropout method.”WARNReviewer 3· 80% conf
The trial design is robust with randomization, blinding, and stratification described. However, a few criteria relevant to human trials are inadequately reported: the a priori power analysis is described but the effect size justification is incomplete, and while the trial is clearly not a bench study, the criteria for blinding levels, inclusion/exclusion, controls, and independent replication are met or not applicable.
Evidence
direct quote[Methods, Trial Design]
“Participants were randomly assigned 1:1:1 to receive baxdrostat 1 mg, baxdrostat 2 mg, or placebo once daily. Randomization was stratified by baseline hypertension status ... and baseline seated-SBP.”direct quote[Methods, Statistical Analyses]
“It was estimated that 720 participants would need to be randomized to achieve 98% power to detect a mean (standard deviation [SD]) difference of 6 (15) mmHg for change from baseline in seated-SBP at week 12 in favor of baxdrostat versus placebo using a two-sample t-test with a two-sided significance level of 0.025.”direct quote[Methods, Trial Design]
“The trial enrolled men and women aged ≥18 years with either uncontrolled or resistant hypertension, defined by a mean seated-SBP ≥140 mmHg and <170 mmHg despite treatment with maximally tolerated doses of either 2 (uncontrolled hypertension) or ≥3 (resistant hypertension) antihypertensive medications... Full inclusion and exclusion criteria are in the Supplementary Appendix.”