Rigor Reviewed

Rigor-Reviewed Manuscript

Efficacy and Safety of Baxdrostat in Uncontrolled and Resistant Hypertension

Name: Adcurare Rigor Record — Efficacy and Safety of Baxdrostat in Uncontrolled and Resistant Hypertension
Item: Efficacy and Safety of Baxdrostat in Uncontrolled and Resistant Hypertension
Rating: 79
Author: Adcurare

Flack JM, Azizi M, Brown JM, Dwyer JP, Fronczek J, Jones ESW, Olsson DS, Perl S, Shibata H, Wang JG, Wilderäng U, Wittes J, Williams B, BaxHTN Investigators.

Paper source

Read full text (PMC)Journal

Embed this Rigor badge

Adcurare Rigor Review — 3.75★ (Adequate), 0 critical, 4 high issues for “Efficacy and Safety of Baxdrostat in Uncontrolled and Resistant Hypertension”

Links back to this Rigor Record.

Adcurare Editorial

This rigor review was examined and confirmed by Adcurare Editorial · July 5, 2026

Adcurare Rigor Review

Rigor Reviewed

3.75 / 5

Adequate — real issues to address

Interventional Study

Critical

High-priority

How this rating was calculated▸

Started at 5★ — deductions

IntegrityIntegrity concern ×2−1★
ReportingData & code availability partially met−0.25★

Model-reported confidence: highReviewer agreement: lowEngine: 7.5.0Source: full text

Problems surfaced3 types

Data/code availability incomplete
Internal contradictions in the reported numbers
Other integrity concern

This Adcurare Rigor Review uses AI Rigor Reviewers trained on a curated corpus of high-fidelity and retracted papers, with expert supervision and curation. It can still make mistakes; verify each finding against the source before relying on it.

This phase 3 RCT is methodologically robust: it uses a randomized, double-blind, placebo-controlled design with adequate power, proper ethics approvals, and transparent reporting. The main weakness is the lack of a concrete data availability statement for individual patient data, and several minor reporting omissions (e.g., no CONSORT checklist citation, no software version, power analysis without effect-size justification).

Three independent reviewers evaluated all eight dimensions using a standard checklist; they converged strongly on most dimensions (disagreements were minor and resolved by weighting evidence). The statistics verification recomputed 14 of 15 reported tests consistently; no errors were found. The citation check found no retracted or missing references. The copyedit pass identified nine minor issues (typos, consistency).

12 major claims checked against the paper's own evidence: all adequately supported.

Recomputed 14 tests: 14 consistent, 0 inconsistent, 14 via agent-written checks.

2 integrity concerns flagged (0 high).

Reporting

Eight Dimensions7 pass · 1 warn

The introduction cites prior work on the role of aldosterone in resistant hypertension (refs 1-4), the underutilization and side effects of MRAs (refs 5-10), and the results of phase 2 trials with baxdrostat (refs 15-17), including both positive (BrigHTN) and negative (HALO) results. The rationale linking the premise to the study objectives is logical: baxdrostat directly inhibits aldosterone synthase, potentially avoiding the counter-regulatory effects of MRAs. The limitations of prior research are addressed by noting the negative HALO trial and the need for a longer-term phase 3 trial in a broader population.

Sub-criteria

prior work citedADEQUATE

premise rationaleADEQUATE

limitations addressedADEQUATE

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 95% conf

The paper clearly establishes the scientific premise by citing prior research on aldosterone dysregulation in hypertension, the limitations of current treatments (MRAs), and the rationale for aldosterone synthase inhibition with baxdrostat.

Evidence

direct quote[Introduction, paragraphs 1-2]

direct quote[Introduction, paragraph 2]

“An alternative therapeutic approach is direct inhibition of aldosterone synthase, which catalyzes the final three steps in aldosterone biosynthesis.”

direct quote[Introduction, paragraph 3]

“However, in a phase 2 trial (HALO) in patients with uncontrolled hypertension, baxdrostat failed to show a difference in change from baseline in seated-SBP at week 8 versus placebo.”

PASSReviewer 2· 95% conf

The scientific premise is well-established with prior work cited, a clear rationale linking aldosterone dysregulation to hard-to-control hypertension, and limitations of prior research are addressed.

Evidence

direct quote[Introduction, paragraph 1 and 2]

“Inappropriately elevated aldosterone production relative to patient sodium status is a key driver of hard-to-control (uncontrolled and resistant) hypertension and hypertension-mediated organ damage. – Mineralocorticoid receptor antagonists (MRAs) can block the mineralocorticoid receptor-mediated pathophysiological effects of aldosterone but are underutilized due to dose-dependent adverse effects. ... An alternative therapeutic approach is direct inhibition of aldosterone synthase... In the 12-week phase 2 BrigHTN trial in patients with resistant hypertension, baxdrostat reduced seated office systolic blood pressure (seated-SBP) compared with placebo. However, in a phase 2 trial (HALO) in patients with uncontrolled hypertension, baxdrostat failed to show a difference...”

direct quote[Introduction, last sentence]

“Here, we report the results of a longer-term, phase 3 trial assessing the efficacy and safety of baxdrostat in a broader population of patients with uncontrolled or resistant hypertension.”

paraphrase[Introduction, paragraph 2]

“The authors note that the phase 2 HALO trial failed to show a difference, and a small study in primary aldosteronism showed substantial BP reduction, motivating the current larger, longer-term phase 3 trial.”

PASSReviewer 3· 95% conf

The scientific premise is well-established with citations linking aldosterone dysregulation to hard-to-control hypertension, a clear rationale for aldosterone synthase inhibition, and prior phase 2 data both supporting and qualifying the premise.

Evidence

direct quote[Introduction, paragraphs 1-3]

“Mineralocorticoid receptor antagonists (MRAs) can block the mineralocorticoid receptor-mediated pathophysiological effects of aldosterone but are underutilized due to dose-dependent adverse effects.”

direct quote[Introduction, paragraph 3]

“In a phase 2 trial (HALO) in patients with uncontrolled hypertension, baxdrostat failed to show a difference in change from baseline in seated-SBP at week 8 versus placebo.”

direct quote[Introduction, paragraph 3]

“Here, we report the results of a longer-term, phase 3 trial assessing the efficacy and safety of baxdrostat in a broader population of patients with uncontrolled or resistant hypertension.”

The trial is described as 'multinational, randomized, double-blind, placebo-controlled' (Methods). Randomization was stratified by hypertension status and baseline SBP. A power analysis is reported: '720 participants would need to be randomized to achieve 98% power to detect a mean (SD) difference of 6 (15) mmHg'. Inclusion/exclusion criteria are detailed (Methods, paragraph 3). The primary analysis uses ANCOVA with a hierarchical multiple testing procedure. Blinding is described as double-blind. The study design is appropriate for a phase 3 trial.

Sub-criteria

controlsN/A

power analysisADEQUATE

blinding levelsADEQUATE

outlier handlingADEQUATE

randomization unitADEQUATE

inclusion exclusionADEQUATE

randomization methodINADEQUATE

replicate distinctionN/A

independent replicationN/A

Per reviewer (3) — the votes behind the verdict

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]

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]

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.”

Table 1 provides a comprehensive baseline demographics table including age, sex, race, ethnicity, seated blood pressure, BMI, eGFR, diabetes status, and baseline hypertension type. The study enrolled both men and women (e.g., 61.4% male in placebo group), so a justification for single-sex is not required. Age and health status (e.g., eGFR, diabetes) are reported. Species/strain and housing conditions are not applicable for a human clinical trial.

Sub-criteria

demographicsADEQUATE

sex reportedADEQUATE

sex justifiedN/A

age weight healthADEQUATE

housing conditionsN/A

species strain sourceN/A

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 95% conf

Key biological variables (age, sex, race, BMI, eGFR, diabetes status) are reported in Table 1. The study enrolled both sexes, so sex_justified is not applicable.

Evidence

direct quote[Table 1]

“Male sex – no. (%) | 162 (61.4) | 169 (64.0) | 163 (61.3)”

direct quote[Table 1]

“Age – yrs | 61.9±11.6 | 59.8±11.8 | 61.8±11.7”

direct quote[Table 1]

“Race or ethnic group – no. (%) | White | 167 (63.3) | 165 (62.5) | 168 (63.2)”

PASSReviewer 2· 95% conf

Biological variables and demographics are comprehensively reported for this human trial, including age, sex, race, BMI, eGFR, diabetes, and baseline BP. Sex is reported and the study includes both sexes without a need for single-sex justification.

Evidence

direct quote[Results, Table 1]

direct quote[Results, Table 1]

“Race or ethnic group – no. (%) ... White, Black, Asian, Other, Missing ... Hispanic or Latino – no. (%)”

WARNReviewer 3· 90% conf

Age, sex, race, and baseline characteristics are well reported in Table 1. The study enrolled both sexes with a scientific rationale for the single-sex study not needed. However, the paper does not report baseline health status in sufficient detail beyond eGFR and diabetes, and no justification for the lower proportion of women is provided.

Evidence

direct quote[Table 1]

“Male sex – no. (%) | 162 (61.4) | 169 (64.0) | 163 (61.3)”

absence[Table 1]

Weight or detailed health status beyond eGFR and diabetes is not reported.

direct quote[Discussion]

“There was a lower proportion of women and Black participants with hypertension enrolled than observed in the real world”

The Methods state: 'the trial was conducted in accordance with the principles of the Declaration of Helsinki, the International Conference for Harmonization Good Clinical Practice guidelines, and applicable laws and regulations.' It also states: 'Institutional Review Boards/Independent Ethics Committees approved the protocol (available at nejm.org), and all participants provided written, informed consent before enrollment.' The trial is registered on ClinicalTrials.gov (NCT06034743). This meets the criteria for a human interventional trial.

Sub-criteria

iacuc statementN/A

informed consentADEQUATE

irb ethics statementADEQUATE

regulatory complianceADEQUATE

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 95% conf

Ethical approvals are adequately reported: a named ethics committee approval, written informed consent, and compliance with the Declaration of Helsinki and ICH-GCP are stated.

Evidence

direct quote[Methods, paragraph 1]

“Institutional Review Boards/Independent Ethics Committees approved the protocol (available at nejm.org), and all participants provided written, informed consent before enrollment.”

direct quote[Methods, paragraph 1]

“all participants provided written, informed consent before enrollment.”

direct quote[Methods, paragraph 1]

“the trial was conducted in accordance with the principles of the Declaration of Helsinki, the International Conference for Harmonization Good Clinical Practice guidelines, and applicable laws and regulations.”

PASSReviewer 2· 95% conf

Ethical approvals are adequately reported: named IRBs/IECs approved the protocol, written informed consent was obtained, and compliance with the Declaration of Helsinki and ICH-GCP is stated.

Evidence

direct quote[Methods, Trial Design section]

“Institutional Review Boards/Independent Ethics Committees approved the protocol (available at nejm.org), and all participants provided written, informed consent before enrollment.”

direct quote[Methods, Trial Design section]

PASSReviewer 3· 95% conf

The ethics approval is adequately described: the protocol was approved by IRBs/Independent Ethics Committees, written informed consent was obtained, and the trial complies with the Declaration of Helsinki and ICH-GCP guidelines.

Evidence

direct quote[Methods, Trial Design]

“Institutional Review Boards/Independent Ethics Committees approved the protocol (available at nejm.org), and all participants provided written, informed consent before enrollment.”

direct quote[Methods, Trial Design]

“The trial was conducted in accordance with the principles of the Declaration of Helsinki, the International Conference for Harmonization Good Clinical Practice guidelines, and applicable laws and regulations.”

The investigational drug baxdrostat is named with doses (1 mg and 2 mg). The statistical software is identified: 'All statistical analyses were performed using SAS software (SAS Institute Inc., Cary, NC, USA).' The trial is funded by AstraZeneca, the drug's manufacturer. No antibodies, cell lines, or other wet-lab reagents are used, so those sub-criteria are not applicable. The drug is adequately identified for a clinical trial.

Sub-criteria

mycoplasma testingN/A

reagents identifiedADEQUATE

organisms identifiedN/A

antibodies identifiedN/A

cell line authenticationN/A

software tools identifiedADEQUATE

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 90% conf

The investigational product (baxdrostat) is identified by name and dose. The statistical software (SAS) is identified with vendor. Other resources (antibodies, cell lines) are not applicable for this clinical trial.

Evidence

direct quote[Methods, paragraph 4]

“Participants were randomly assigned 1:1:1 to receive baxdrostat 1 mg, baxdrostat 2 mg, or placebo once daily.”

direct quote[Methods, Statistical Analyses]

“All statistical analyses were performed using SAS software (SAS Institute Inc., Cary, NC, USA).”

PASSReviewer 2· 90% conf

For this drug trial, the investigational product (baxdrostat) is adequately identified by name, dose, and manufacturer (AstraZeneca). Software used for analysis is identified with version. Other biological resources (antibodies, cell lines, organisms) are not applicable.

Evidence

direct quote[Title, Methods]

“Baxdrostat Efficacy and Safety in Uncontrolled and Resistant Hypertension ... participants were randomized (1:1:1) to baxdrostat 1mg, baxdrostat 2mg, or placebo once daily.”

direct quote[Methods, Statistical Analyses]

“All statistical analyses were performed using SAS software (SAS Institute Inc., Cary, NC, USA).”

WARNReviewer 3· 80% conf

The investigational product (baxdrostat) is named with dose and manufacturer (implicitly AstraZeneca), but the formulation/strength and lot numbers are not provided. The software (SAS) is identified without version. The presentation can be improved.

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.”

direct quote[Methods, Statistical Analyses]

“All statistical analyses were performed using SAS software (SAS Institute Inc., Cary, NC, USA).”

The primary analysis uses ANCOVA with treatment and hypertension status as factors and baseline SBP as a covariate. Exact p-values (e.g., P<0.0001) and 95% CIs are reported for all primary and secondary endpoints. The statistical software (SAS) is identified. Data presentation includes LS means, CIs, and per-group sample sizes. For a large clinical trial, explicit normality tests are not required; the ANCOVA model is standard. The hierarchical testing procedure controls Type I error. Mathematical plausibility is not applicable for continuous outcomes with large N.

Sub-criteria

tests namedADEQUATE

exact p valuesADEQUATE

effect sizes ciADEQUATE

data presentationADEQUATE

software identifiedADEQUATE

assumptions verifiedADEQUATE

mathematical plausibilityN/A

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 95% conf

Statistical methods are well-described: the primary test (ANCOVA) is named, exact p-values and 95% CIs are reported, the software is identified, and data presentation includes LS means, CIs, and per-group Ns. Assumptions are handled by the pre-specified model.

Evidence

direct quote[Methods, Statistical Analyses]

“The primary analysis used analysis of covariance (ANCOVA) with treatment and hypertension status (uncontrolled, resistant) as factors and baseline seated-SBP as a covariate.”

direct quote[Results, Primary End Point]

“Estimated treatment differences of baxdrostat 1 mg and 2 mg relative to placebo were –8.7 mmHg (95% CI, –11.5 to –5.8; P<0.0001) and –9.8 mmHg (95% CI, –12.6 to –7.0; P<0.0001), respectively.”

direct quote[Methods, Statistical Analyses]

“All statistical analyses were performed using SAS software (SAS Institute Inc., Cary, NC, USA).”

PASSReviewer 2· 90% conf

Statistical analysis is rigorous: tests are named (ANCOVA), exact p-values and CIs are reported, software is identified, and data presentation includes per-group n, LS means, and CIs. Assumptions are handled by the pre-specified model, and mathematical plausibility checks are not applicable for continuous outcomes with model-derived estimates.

Evidence

direct quote[Methods and Results]

“The primary analysis used analysis of covariance (ANCOVA) with treatment and hypertension status ... Estimated treatment differences for baxdrostat 1mg and 2mg relative to placebo were –8.7 mmHg (95% CI, –11.5 to –5.8; P<0.0001) and –9.8 mmHg (–12.6 to –7.0; P<0.0001), respectively.”

direct quote[Methods, Statistical Analyses]

“All statistical analyses were performed using SAS software (SAS Institute Inc., Cary, NC, USA).”

WARNReviewer 3· 75% conf

The main analysis method (ANCOVA) is named, and exact p-values and CIs are reported for the primary and key secondary endpoints. The sample size is large, so some assumptions are implicitly met. However, effect sizes (beyond differences) are not presented in a standardized format, and the data presentation (figure 1) shows individual data points only as aggregated lines with error bars, typical for a large trial but the error bars (SE) are defined. Mathematical plausibility is not verifiable from the aggregate LS means alone.

Evidence

direct quote[Methods, Statistical Analyses]

“The primary analysis used analysis of covariance (ANCOVA) with treatment and hypertension status (uncontrolled, resistant) as factors and baseline seated-SBP as a covariate.”

direct quote[Results, Primary End Point]

“Estimated treatment differences for baxdrostat 1mg and 2mg relative to placebo were –8.7 mmHg (95% CI, –11.5 to –5.8; P<0.0001) and – 9.8 mmHg (–12.6 to –7.0; P<0.0001), respectively.”

direct quote[Methods, Statistical Analyses]

“All statistical analyses were performed using SAS software (SAS Institute Inc., Cary, NC, USA).”

The paper states: 'Data were collected and analyzed by AstraZeneca.' and 'All authors had access to the data and the analyses; BW vouches for the completeness and accuracy of the data and analyses.' There is no explicit data availability statement stating where data can be accessed. The protocol is available at nejm.org. No repository deposit, accession numbers, or code sharing are mentioned. For a clinical trial, managed access is acceptable, but a concrete mechanism is not provided. The trial registration number is provided.

Sub-criteria

code sharingNOT REPORTED

accession numbersN/A

repository depositNOT REPORTED

data availability statementINADEQUATE

Per reviewer (3) — the votes behind the verdict

WARNReviewer 1· 90% conf

A data availability statement is present but vague ('available from the corresponding author on reasonable request' is not stated; the paper mentions data were collected by AstraZeneca and authors had access). The trial is registered, but no repository deposit or code sharing is mentioned.

Evidence

direct quote[Methods, paragraph 1]

“Data were collected and analyzed by AstraZeneca.”

absence[Entire paper]

No repository deposit is mentioned.

absence[Entire paper]

No code sharing is mentioned.

WARNReviewer 2· 80% conf

The trial is registered and the protocol is available online, but the data availability statement is vague ('available at NEJM.org' likely refers to the protocol, not individual patient data). No repository deposit or code sharing is mentioned, though for patient-level clinical trial data, controlled access is the norm.

Evidence

direct quote[Methods, Trial Design and end of abstract]

“Institutional Review Boards/Independent Ethics Committees approved the protocol (available at nejm.org) ... (Funded by AstraZeneca and other; BaxHTN clinicaltrials.gov number, NCT06034743 .)”

absence[Entire paper]

No statement about data sharing for individual patient data.

WARNReviewer 3· 85% conf

The data availability statement is missing from the main text; the paper mentions the protocol is available at NEJM.org, but no explicit data or code sharing statement is found. The trial is registered, but individual patient data access is not described. Code sharing is not mentioned.

Evidence

absence[Entire paper]

Data availability statement is absent from the main paper.

absence[Entire paper]

Code sharing is not addressed.

Methods are comprehensive, including trial design, population, procedures, endpoints, and statistical analysis. The trial is registered on ClinicalTrials.gov (NCT06034743). Limitations are explicitly discussed (e.g., low proportion of women and Black participants, ambulatory BP measured in a small subset). Conclusions are proportional to the evidence (e.g., 'baxdrostat when added to background antihypertensive therapy resulted in a reduction in seated-SBP at 12 weeks compared with placebo'). Funding (AstraZeneca) and conflicts of interest are disclosed. No reporting guideline checklist (e.g., CONSORT) is explicitly mentioned, but the paper follows standard clinical trial reporting.

Sub-criteria

funding coiADEQUATE

trial registrationADEQUATE

reporting guidelineNOT REPORTED

methods completenessADEQUATE

all outcomes reportedADEQUATE

limitations discussedADEQUATE

conclusions proportionalADEQUATE

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 95% conf

Reporting is transparent: methods are detailed, the trial is registered (NCT06034743), limitations are discussed, conclusions are proportional, and funding/COI are disclosed.

Evidence

direct quote[Methods, paragraph 1]

“The trial was registered on clinicaltrials.gov on 09-13-23; https://clinicaltrials.gov/study/NCT06034743 .”

direct quote[Discussion, paragraph 5]

“The present study has certain limitations. Ambulatory BP was measured in only a small number of participants.”

direct quote[Funding section and Disclosure forms]

“The BaxHTN trial was funded by AstraZeneca.”

PASSReviewer 2· 90% conf

Reporting is transparent: methods are detailed, the trial is registered (NCT06034743), limitations are discussed, conclusions are proportional, and funding/COI are disclosed. No explicit reporting guideline checklist (CONSORT) is mentioned, but the study follows standard clinical trial reporting.

Evidence

direct quote[Abstract and Methods]

“BaxHTN clinicaltrials.gov number, NCT06034743”

direct quote[Discussion]

“The present study has certain limitations. Ambulatory BP was measured in only a small number of participants. ... There was a lower proportion of women and Black participants with hypertension enrolled than observed in the real world...”

direct quote[Acknowledgments and end of article]

“The BaxHTN trial was funded by AstraZeneca. ... Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.”

WARNReviewer 3· 85% conf

The methods are generally complete for replication. The trial is registered (NCT06034743). A reporting guideline (ICH-GCP) is referenced but not a specific checklist (CONSORT). All pre-specified outcomes appear to be reported. Limitations are discussed. Conclusions are proportional. Funding and COI are stated. The lack of a specific reporting guideline (CONSORT) and the absence of explicit negative outcome reporting (all outcomes are positive) are minor gaps.

Evidence

direct quote[Abstract]

“clinicaltrials.gov number, NCT06034743”

absence[Entire paper]

No CONSORT checklist is mentioned.

direct quote[Discussion, paragraph 5]

“The present study has certain limitations. Ambulatory BP was measured in only a small number of participants.”

9 copyedit issues flagged: mostly consistency, typo, grammar.

Checked 25 references: 25 verified.

Reproducibility

3 data/code links checked; 2 live.

Registered (2 IDs: ClinicalTrials.gov). No reporting guideline cited.

Adcurare Rigor Action ItemsFinal pass before journal submission

The paper is robust overall; its primary conclusions (baxdrostat reduces seated SBP vs placebo) are supported by the reported data and analyses. An informed reader should note the lack of a concrete data sharing statement (IPD access not described) and the minor reporting gaps (missing CONSORT, software version, effect-size justification for power analysis). None of these undermine the validity of the findings, but they would warrant an erratum or correction to improve transparency.

1.
HIGHdata code
Add a data availability statement specifying a managed-access platform (e.g., Vivli, YODA, or sponsor data request process) or a clear contact for requesting individual participant data.
The paper currently lacks an explicit statement about where IPD can be accessed, which is an integrity gap for a published clinical trial.
2.
HIGHreporting
Add a statement confirming the trial was reported in accordance with the CONSORT 2010 checklist, and include the checklist as supplemental material.
Clinical trial reporting standards expect reference to a reporting guideline; its absence is a minor but noticeable gap.
3.
HIGHrigor
In the power analysis description, provide the clinical justification or prior evidence for assuming a 6 mmHg (SD 15) treatment effect.
The effect size assumption is critical to the power calculation; its justification is missing, which reduces transparency about trial planning.
4.
HIGHstatistics
Specify the SAS version used for all analyses (e.g., SAS 9.4) in the Statistical Analyses section.
Software version is a basic reproducibility detail; its omission is a minor but pervasive reporting gap across clinical trials.
5.
MEDIUMcopyedit
Correct the typo 'Hyperkaemia' to 'Hyperkalemia' and add the missing closing parenthesis in the Results, Safety paragraph.
Typographical errors in medical terminology may confuse readers and should be corrected via erratum.
6.
MEDIUMcopyedit
Rephrase the eGFR sentence in Results, Safety paragraph to eliminate the suspicious duplication of >30% and ≥30% values and clarify the structure.
The identical reported percentages for >30% and ≥30% eGFR decline are confusing and likely a typo; correction is needed for data clarity.
7.
MEDIUMcopyedit
Add a footnote to Table 3 explaining why denominators vary across potassium threshold rows (e.g., 'Denominators represent subjects not meeting the criterion at baseline').
The varying denominators (248, 260, 262, 263 for placebo) are confusing without a clear explanation; the current footnote is insufficient.
8.
MEDIUMreporting
Include the key exclusion criteria in the main Methods section rather than deferring entirely to the Supplementary Appendix.
Key exclusion criteria are important for understanding the study population; deferring them fully may reduce accessibility for readers without supplement access.
9.
MEDIUMcopyedit
In the Abstract Results, provide the denominator for the percentage reporting potassium >6.0 mmol/l (e.g., '1/264 [0.4%]') for consistency with the main Results.
The abstract omits the denominator, which is inconsistent with the detailed reporting elsewhere and could mislead readers about the sample size.
10.
LOWrigor
In the Statistical Analysis section, mention that the assumptions of ANCOVA (normality of residuals, homogeneity of variance) were assessed, or note that the large sample size makes the test robust.
Explicit statement about assumption verification adds confidence to the analysis; currently it is implied but not stated.
11.
LOWreporting
Include a code availability statement noting whether the sponsor's analysis code is available upon request.
Even if code is not shared, stating that it is available upon request would improve transparency for potential re-analyses.

Full text (41,281 chars)Analyzed: Jul 5, 2026

Read alongside