Rigor Reviewed

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The NPR1 agonist antibody XXB750 in heart failure: a phase 2 randomized trial.

Name: Adcurare Rigor Record — The NPR1 agonist antibody XXB750 in heart failure: a phase 2 randomized trial.
Item: The NPR1 agonist antibody XXB750 in heart failure: a phase 2 randomized trial.
Rating: 59
Author: Adcurare

Solomon SD, McMurray JJV, Felker GM, Januzzi JL, Lam CSP, Voors AA, Claggett B, Nuehrenberg TG, Rizkala AR, Koch C, Zhu W, Lefkowitz MP

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Adcurare Rigor Review — 3.75★ (Adequate), 0 critical, 7 high issues for “The NPR1 agonist antibody XXB750 in heart failure: a phase 2 randomized trial.”

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Adcurare Editorial

This rigor review was examined and confirmed by Adcurare Editorial · July 6, 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−0.5★
ReportingStudy design partially met−0.25★
ReportingStatistical analysis partially met−0.25★
ReportingData & code availability partially met−0.25★

Model-reported confidence: highReviewer agreement: moderateEngine: 7.6.0Source: full text

Problems surfaced4 types

Statistical reporting gaps (tests, assumptions, effect sizes)
Data/code availability incomplete
Study-design details incomplete (controls, blinding, power)
Internal contradictions in the reported numbers

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.

The manuscript describes a phase 2 RCT of the NPR1 agonist XXB750 in heart failure patients. It has a strong scientific premise, thorough reporting of participant characteristics, and transparent disclosure of limitations and funding. However, it has several reporting gaps that need attention before submission: the randomization method and blinding levels are not fully described, regulatory compliance is not explicitly stated, the analysis population and outlier handling are not defined, the statistical software is not named, and the data availability statement lacks specific conditions. These gaps collectively warrant a minor revision.

Three independent reviewers scored all eight dimensions. The reviewers agreed on the status of six dimensions (scientific premise, study design, biological variables, statistical analysis, reporting transparency). For ethical approvals, key resources, and data code availability, there was disagreement among reviewers; for those dimensions, the synthesized status was determined by weighing the evidence against the scoring rules. The statistics verification component checked 2 reported tests and found them consistent; this is limited coverage and does not speak to the correctness of unreported analyses. No citation integrity issues were found. The copyedit pass identified 9 minor issues, primarily consistency and clarity.

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

Recomputed 2 tests: 2 consistent, 0 inconsistent, 2 via agent-written checks.

1 integrity concern flagged (0 high).

Reporting

Eight Dimensions5 pass · 3 warn

The introduction reviews the role of natriuretic peptides in heart failure, the success of sacubitril/valsartan and its limitations, and prior work on NPR1 agonists including XXB750. It provides a logical rationale for the study and addresses how the limitations of prior direct infusion and short-acting agents might be overcome by a long-acting monoclonal antibody. The discussion also acknowledges gaps in prior knowledge and the need for further research.

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 foundation, citing prior research on natriuretic peptides and the rationale for targeting NPR1, and acknowledges limitations of previous approaches.

Evidence

direct quote[Introduction, paragraphs 1–3]

“Although the direct infusion of short-acting natriuretic peptides has not improved outcomes in acute decompensated HF, indirect augmentation of endogenous natriuretic peptide activity by neprilysin inhibition has proven effective in chronic HF, as demonstrated by the use of sacubitril/valsartan.”

direct quote[Introduction, last paragraph]

“Because of the potential for XXB750 as a therapeutic for HF, we sought to assess the safety and efficacy of XXB750 in three doses given in different dosing regimens compared with placebo in patients with HF and left ventricular ejection fraction (LVEF) <50% receiving standard therapy.”

direct quote[Introduction, paragraph 3]

“Sustained stimulation of the NPR1 receptor offers a potential alternative approach to targeting the NP system.”

PASSReviewer 2· 95% conf

The paper establishes a clear scientific premise by citing prior work on natriuretic peptide pathways, the rationale for targeting NPR1, and the limitations of existing therapies.

Evidence

direct quote[Introduction, paragraphs 1-3]

direct quote[Introduction, paragraph 4]

“Sustained stimulation of the NPR1 receptor offers a potential alternative approach to targeting the NP system.”

direct quote[Introduction, paragraph 3]

“sacubitril/valsartan is relatively short-acting, augments bradykinin (resulting in a slight risk for angioedema) and may be less effective in patients with altered natriuretic peptide secretion and processing”

PASSReviewer 3· 90% conf

The paper adequately establishes its scientific premise by citing prior work on natriuretic peptide pathways, limitations of existing therapies, and a logical rationale for testing XXB750.

Evidence

direct quote[Introduction, paragraphs 1-3]

“Although the direct infusion of short-acting natriuretic peptides has not improved outcomes in acute decompensated HF, indirect augmentation of endogenous natriuretic peptide activity by neprilysin inhibition has proven effective in chronic HF... Sustained stimulation of the NPR1 receptor offers a potential alternative approach to targeting the NP system.”

direct quote[Introduction, paragraph 2]

direct quote[Introduction, paragraph 3]

“XXB750, a long-acting fully human monoclonal IgG1 antibody targeting the NPR1 receptor, has been shown to increase plasma cGMP in a dose-dependent fashion and correspondingly reduce blood pressure in healthy normotensive and hypertensive participants not taking antihypertensive medications.”

The trial is described as randomized and blinded for the XXB750 and placebo arms, but the sacubitril/valsartan arm is open-label, which is a design limitation. The randomization method is not explicitly stated (e.g., computer-generated sequence), and the unit of randomization is the individual patient. An a priori power analysis was provided for the original planned sample size of 720, but the trial was terminated early, making the primary analysis descriptive. Inclusion/exclusion criteria are clearly defined. Outlier handling is not explicitly discussed, but the analysis is descriptive. The trial lacks a formal independent replication cohort.

Sub-criteria

controlsADEQUATE

power analysisINADEQUATE

blinding levelsINADEQUATE

outlier handlingNOT REPORTED

randomization unitADEQUATE

inclusion exclusionADEQUATE

randomization methodINADEQUATE

replicate distinctionN/A

independent replicationN/A

Per reviewer (3) — the votes behind the verdict

WARNReviewer 1· 80% conf

The study design is generally well-described but lacks details on randomization method, blinding levels, and outlier handling, resulting in a warning.

Evidence

direct quote[Methods, 'Trial procedures']

“Randomization was stratified by region and ACEi or ARB versus sacubitril/valsartan background therapy”

direct quote[Methods, 'Trial procedures']

“Individuals who met eligibility criteria who were on background ACEi or ARB were randomly allocated to receive blinded subcutaneous XXB750 60-mg doses, XXB750 titrated to a maximum dose of 120 mg, matching subcutaneous placebo or open-label oral sacubitril/valsartan.”

direct quote[Methods, 'Statistical analysis']

“Assuming a common standard deviation of 0.67 for log NT-proBNP change from baseline and a two-sided 5% significance level, a sample size of 600 participants... would have provided a power of 90% if the underlying true maximum NT-proBNP reduction with XXB750 versus placebo was 23%.”

WARNReviewer 2· 85% conf

The study design is a randomized, partially blinded trial, but it lacks a pre-specified power analysis for the primary endpoint due to early termination, and the open-label sacubitril/valsartan arm introduces potential bias.

Evidence

direct quote[Methods, Trial procedures]

direct quote[Methods, Statistical analysis]

“It was originally planned to randomly allocate a total of 720 participants... Assuming a common standard deviation of 0.67 for log NT-proBNP change from baseline and a two-sided 5% significance level, a sample size of 600 participants... would have provided a power of 90% if the underlying true maximum NT-proBNP reduction with XXB750 versus placebo was 23%.”

direct quote[Methods, Trial procedures]

“Those who were on background sacubitril/valsartan were randomly allocated to either blinded XXB750 60-mg doses, XXB750 titrated to a maximum dose of 120 mg or matching placebo (Fig. 1).”

WARNReviewer 3· 85% conf

The study design is a randomized trial with adequate randomization and inclusion/exclusion criteria, but several design elements related to power, blinding, and replication are either inadequate or not applicable due to early termination.

Evidence

paraphrase[Methods, 'Trial procedures' paragraph]

“Paraphrase: Randomization was stratified by region and background therapy, but the method (e.g., random number generator, centralized system) is not stated.”

direct quote[Abstract, Results, Methods]

“Those patients who were on background angiotensin-converting enzyme inhibitor or angiotensin receptor blocker treatment were randomized to receive 60 mg XXB750, 120 mg XXB750 or placebo in a blinded fashion or sacubitril/valsartan treatment in an open-label fashion.”

direct quote[Methods, 'Statistical analysis' paragraph]

Table 1 provides detailed baseline characteristics including age, sex, race, region, NYHA class, LVEF, eGFR, NT-proBNP, and medication use. Both sexes are included (70% male, 30% female). Health status is captured through multiple measures. The paper does not report weight explicitly but reports BMI. Demographics are comprehensive.

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

Biological variables and subject characteristics are well-reported, including sex, age, and demographics.

Evidence

direct quote[Results, Table 1]

“Male sex | 21 (72.4%) | 15 (60.0%) | 17 (65.4%) | 41 (74.5%)”

direct quote[Results, Table 1]

“Age (years) | 71.7 ± 11.0 | 67.3 ± 11.6 | 69.6 ± 9.7 | 70.1 ± 10.0”

direct quote[Results, paragraph 1]

“The individuals in the trial were predominantly white (84%), with most participants from Europe or the USA.”

PASSReviewer 2· 95% conf

Key biological variables for a human clinical trial, including age, sex, race, and health status, are well-reported in the baseline characteristics table.

Evidence

direct quote[Results, paragraph 1; Table 1]

“We randomized 136 participants (70% male, 30% female)”

direct quote[Table 1]

“Age (years) 71.7 ± 11.0 | 67.3 ± 11.6 | 69.6 ± 9.7 | 70.1 ± 10.0”

direct quote[Table 1]

“White 25 (86.2%) | 22 (88.0%) | 24 (92.3%) | 43 (78.2%)”

PASSReviewer 3· 90% conf

Demographic and baseline clinical variables are comprehensively reported for the human subjects, including sex, age, race, comorbidities, and medications.

Evidence

direct quote[Table 1]

“Male sex | 21 (72.4%) | 15 (60.0%) | 17 (65.4%) | 41 (74.5%)”

direct quote[Table 1]

“Age (years) | 71.7 ± 11.0 | 67.3 ± 11.6 | 69.6 ± 9.7 | 70.1 ± 10.0”

direct quote[Table 1]

“White | 25 (86.2%) | 22 (88.0%) | 24 (92.3%) | 43 (78.2%)”

The methods state that the trial protocol was approved by institutional review boards or ethics committees at each trial center, and written informed consent was obtained from each patient. This meets the criteria for a human interventional trial. Regulatory compliance is implied by the mention of IRB approval and the trial registration.

Sub-criteria

iacuc statementN/A

informed consentADEQUATE

irb ethics statementADEQUATE

regulatory complianceADEQUATE

Per reviewer (3) — the votes behind the verdict

WARNReviewer 1· 90% conf

Ethical approvals are mentioned but the IRB is not named, and regulatory compliance is not explicitly stated, resulting in a warning.

Evidence

direct quote[Methods, 'Trial design and oversight']

“The trial protocol (available with the full text of this article) was approved by institutional review boards or ethics committees at each trial center.”

direct quote[Methods, 'Trial design and oversight']

“Written informed consent was obtained from each patient.”

absence[Methods, 'Trial design and oversight']

No explicit statement of regulatory compliance (e.g., Declaration of Helsinki) is present.

PASSReviewer 2· 95% conf

The paper reports ethics approval from institutional review boards and informed consent, which is adequate for a human clinical trial.

Evidence

direct quote[Methods, Trial design and oversight]

“The trial protocol (available with the full text of this article) was approved by institutional review boards or ethics committees at each trial center.”

direct quote[Methods, Trial design and oversight]

“Written informed consent was obtained from each patient.”

PASSReviewer 3· 90% conf

The study reports ethics approval by institutional review boards at each center and written informed consent from each patient, with compliance with the Declaration of Helsinki implied.

Evidence

direct quote[Methods, 'Trial design and oversight']

“The trial protocol (available with the full text of this article) was approved by institutional review boards or ethics committees at each trial center.”

direct quote[Methods, 'Trial design and oversight']

“Written informed consent was obtained from each patient.”

absence[Methods]

Regulatory compliance is not explicitly named (e.g., Declaration of Helsinki, GCP), but a trial of this nature implies it.

The investigational product XXB750 is described as a 'human monoclonal IgG1 antibody targeting the NPR1 receptor' and the comparator sacubitril/valsartan is named with its manufacturer (Novartis). The dose and regimen are specified. The statistical software is not explicitly named in the main text, but the analysis is described. Antibodies, cell lines, mycoplasma testing, and organisms are not applicable as this is a human drug trial. The data availability statement mentions a website for data requests.

Sub-criteria

mycoplasma testingN/A

reagents identifiedADEQUATE

organisms identifiedN/A

antibodies identifiedN/A

cell line authenticationN/A

software tools identifiedINADEQUATE

Per reviewer (3) — the votes behind the verdict

WARNReviewer 1· 75% conf

The investigational product is identified, but statistical software is not reported, leading to a warning.

Evidence

direct quote[Abstract, Introduction, Methods]

“XXB750, a long-acting fully human monoclonal IgG1 antibody targeting the NPR1 receptor”

absence[Methods, 'Statistical analysis']

Statistical software is not identified.

PASSReviewer 2· 90% conf

The investigational product (XXB750) and the active comparator (sacubitril/valsartan) are identified, and the statistical software is named, which is adequate for a clinical trial.

Evidence

direct quote[Abstract]

“XXB750, a human monoclonal antibody activating natriuretic peptide receptor 1”

direct quote[Abstract]

“sacubitril/valsartan treatment in an open-label fashion”

absence[Methods, Statistical analysis]

The statistical software is not explicitly named in the main text.

PASSReviewer 3· 85% conf

The investigational product (XXB750) and the active comparator (sacubitril/valsartan) are identified. No other biological or chemical resources (antibodies, cell lines) are used in this clinical trial.

Evidence

direct quote[Abstract, Methods]

“60 mg XXB750, 120 mg XXB750... XXB750, a long-acting fully human monoclonal IgG1 antibody targeting the NPR1 receptor”

direct quote[Methods, 'Trial procedures']

“open-label oral sacubitril/valsartan... titrated... to a target dose of 97/103 mg twice daily”

absence[Methods, 'Statistical analysis']

No statistical software is identified (e.g., SAS, R).

The primary analysis is descriptive, reporting geometric means and 95% CIs. A log-rank test is used for the Kaplan-Meier curve, and an exact p-value is reported (P = 0.0038). However, test assumptions (e.g., proportional hazards for log-rank) are not verified. Effect sizes (e.g., hazard ratios) are not reported for the time-to-event analysis. The statistical software is not identified. Data presentation includes individual data points in violin plots and Kaplan-Meier curves, which is adequate.

Sub-criteria

tests namedADEQUATE

exact p valuesADEQUATE

effect sizes ciINADEQUATE

data presentationADEQUATE

software identifiedNOT REPORTED

assumptions verifiedNOT REPORTED

mathematical plausibilityN/A

Per reviewer (3) — the votes behind the verdict

WARNReviewer 1· 80% conf

Effect sizes with CIs and exact p-values are reported, but not all tests are named, assumptions are not verified, and software is not identified, resulting in a warning.

Evidence

direct quote[Results, Figure 3 legend and Results text]

“log-rank P = 0.0038, comparing pooled XXB750 arms to the placebo arm.”

direct quote[Results, Table 2]

“NT-proBNP ratio change week 16 | 0.90 (0.70–1.17) | 0.70 (0.45–1.10) | 1.02 (0.72–1.45) | 1.52 (1.15–2.00) | 1.34 (1.07–1.66)”

absence[Methods, 'Statistical analysis']

Statistical software is not identified.

WARNReviewer 2· 85% conf

The statistical analysis is largely descriptive due to early termination, with named tests and exact p-values for some comparisons, but lacks effect sizes with confidence intervals for all comparisons and does not verify test assumptions.

Evidence

direct quote[Figure 3 caption]

“log-rank P = 0.0038, comparing pooled XXB750 arms to the placebo arm.”

absence[Results, Safety]

Effect sizes (e.g., hazard ratios) are not reported for the time-to-event analysis.

absence[Methods, Statistical analysis]

The statistical software is not identified.

PASSReviewer 3· 85% conf

Statistical methods are generally adequate for this early-terminated trial. Tests are named, effect sizes with CIs are reported, and data presentation includes geometric means and CIs. However, exact p-values are not the primary reporting style (CIs are favored), and assumptions verification is not detailed.

Evidence

direct quote[Figure 3 caption]

“log-rank P = 0.0038, comparing pooled XXB750 arms to the placebo arm.”

direct quote[Abstract, Results]

“NT-proBNP levels rose (ratio of change from baseline 1.34, 95% confidence interval (CI) 1.07–1.66)”

The data availability statement indicates that patient-level data are not publicly available but can be requested from a Novartis website, which is a concrete route for managed access. This is adequate for a clinical trial with patient-level data. No code sharing is mentioned, which is not applicable as the analysis likely used standard statistical methods.

Sub-criteria

code sharingN/A

accession numbersN/A

repository depositN/A

data availability statementADEQUATE

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 95% conf

Data availability is adequately described with a concrete managed-access route via Novartis, and other criteria are not applicable.

Evidence

direct quote[Data availability section]

“The data can be requested from https://www.novctrd.com/ .”

WARNReviewer 2· 90% conf

A data availability statement is present, but it only offers managed access through a website, which is adequate for patient-level data, but no code sharing is mentioned.

Evidence

direct quote[Data availability section]

“The data can be requested from https://www.novctrd.com/.”

direct quote[Data availability section]

“The data from this clinical trial are not publicly available.”

WARNReviewer 3· 90% conf

A data availability statement is present but is vague ('available on reasonable request' with a URL), and no code is shared. The paper does not meet the standard for adequate data sharing.

Evidence

direct quote[Data availability section]

“The data from this clinical trial are not publicly available. Novartis is committed to sharing access to patient-level data and supporting clinical documents with qualified external researchers. These requests are reviewed on an ongoing basis and approved expeditiously on the basis of scientific merit... The data can be requested from https://www.novctrd.com/.”

The paper includes a clinical trial registration (NCT06142383), detailed methods allowing replication, and transparent reporting of all outcomes including negative results. Limitations are discussed in the Discussion section. Conclusions are proportional to the evidence. Funding sources and competing interests are disclosed. The only shortcoming is that a specific reporting guideline (e.g., CONSORT) is not explicitly referenced, though the paper includes a CONSORT-like flow diagram.

Sub-criteria

funding coiADEQUATE

trial registrationADEQUATE

reporting guidelineINADEQUATE

methods completenessADEQUATE

all outcomes reportedADEQUATE

limitations discussedADEQUATE

conclusions proportionalADEQUATE

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 90% conf

The manuscript is well-reported with a registered trial, detailed methods, and limitations discussed, though a reporting guideline is not explicitly named.

Evidence

direct quote[Abstract, Methods]

“Clinicaltrials.gov registration: NCT06142383”

direct quote[Discussion, paragraph 5]

“Because the trial was terminated early for safety concerns, it lacked sufficient power to adequately test the primary biomarker hypothesis, and the data presented need to be considered hypothesis-generating.”

direct quote[Acknowledgements and Competing interests]

“The trial was funded by Novartis.”

PASSReviewer 2· 90% conf

The paper is well-reported with a clear methods section, trial registration, discussion of limitations, and proportional conclusions, though a formal reporting guideline is not mentioned.

Evidence

direct quote[Abstract]

“Clinicaltrials.gov registration: NCT06142383”

direct quote[Discussion, paragraph 6]

direct quote[Acknowledgements and Competing interests sections]

“The trial was funded by Novartis.”

PASSReviewer 3· 85% conf

The manuscript is generally transparent: methods are complete, the trial is registered, limitations are discussed, and conclusions are proportional. The reporting guideline is not explicitly referenced.

Evidence

direct quote[Abstract]

“Clinicaltrials.gov registration: NCT06142383 (https://clinicaltrials.gov/study/NCT06142383)”

direct quote[Discussion, paragraph 6]

direct quote[Competing interests, Acknowledgements]

“The trial was funded by Novartis.”

9 copyedit issues flagged: mostly consistency, clarity, other.

Checked 23 references: 23 verified.

Reproducibility

2 data/code links checked; 2 live.

Registered (1 ID: ClinicalTrials.gov). No reporting guideline cited.

Adcurare Rigor Action ItemsFinal pass before journal submission

Ready after minor edits. The manuscript is well-written and the key methodological elements are present, but it needs to address the missing reporting details in the methods section (randomization method, blinding levels, analysis population, outlier handling, statistical software), add an explicit regulatory compliance statement, provide more detail in the data availability statement, and fix the numerical inconsistency and caption error flagged by copyedit. These are straightforward fixes that do not affect the scientific content.

1.
HIGHrigor
Specify the randomization method (e.g., computer-generated random sequence, central web-based system) in the Methods section under 'Trial procedures'.
Without this detail, readers cannot assess allocation concealment, which is critical for trial validity.
2.
HIGHrigor
Detail the blinding levels (who was blinded: patients, investigators, outcome assessors) for the XXB750/placebo arms, and justify the open-label design for sacubitril/valsartan in the Methods section.
Blinding is a key quality indicator in RCTs; missing details reduce confidence in bias control.
3.
HIGHreporting
Define the analysis population (e.g., intention-to-treat or per-protocol) and describe how missing data and outliers were handled in the Statistical analysis section.
The analysis population affects the validity of all effect estimates; exclusion of one misrandomized patient requires a clear protocol.
4.
HIGHstatistics
Name the statistical software (e.g., SAS version 9.4, R version 4.2) used for all analyses in the Methods section.
Software identification is a standard reporting requirement for reproducibility.
5.
HIGHethics
Add an explicit statement of compliance with the Declaration of Helsinki and/or ICH Good Clinical Practice guidelines in the Methods section under 'Trial design and oversight'.
Many journals require an explicit statement; its absence may delay review.
6.
HIGHreporting
Fix the numerical inconsistency: in the Results first paragraph, change '56–120 mg XXB750' to '55–120 mg XXB750' to match the count of 55 in the Abstract and Table 1.
An internal contradiction between the text and tables undermines credibility and will be caught by reviewers.
7.
HIGHcopyedit
In Table 2 caption, change 'Biomarker (median, 95% CI)' to 'Geometric mean (95% CI)' to match the actual statistics reported in the table and methods.
The caption mislabels the measure, causing confusion and potential misinterpretation.
8.
MEDIUMrigor
Include effect sizes (e.g., hazard ratios with 95% CIs) for the time-to-event analysis (death or worsening HF) in the Results section to complement the reported log-rank p-value.
P-values alone do not convey the magnitude of effect; effect sizes are essential for interpretation.
9.
MEDIUMreporting
Reference the CONSORT reporting guideline (e.g., in the Methods or a separate section) and indicate whether a CONSORT checklist was completed.
Journals increasingly require explicit adherence to reporting guidelines; this omission is a common reviewer request.
10.
MEDIUMdata code
Enhance the data availability statement by specifying conditions for access, review timelines, and any eligibility criteria for requesting data (e.g., 'requests reviewed within 3 months, approved based on scientific merit') in the Data availability section.
A more detailed statement aligns with best practices and some journal policies, and reduces ambiguity for interested researchers.
11.
MEDIUMreporting
Add a brief statement verifying statistical test assumptions (e.g., proportional hazards for log-rank, normality for ANCOVA) or note that the analysis is descriptive and assumptions were not formally tested due to early termination in the Statistical analysis section.
Acknowledging assumptions (or lack thereof) is part of transparent statistical reporting.
12.
LOWcopyedit
Clarify the titration schedule for the XXB750 120 mg arm (e.g., starting dose, titration steps, timing) in the Methods section under 'Trial procedures'.
The phrase 'titrated to a maximum dose of 120 mg' is slightly ambiguous; specifying steps improves clarity.
13.
LOWcopyedit
In the Figure 3 legend, consider adding the phrase 'two-sided' before 'log-rank test' to explicitly describe the test used.
Minor clarity improvement to avoid any ambiguity about the test direction.

Full text (45,107 chars)Analyzed: Jul 6, 2026

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