PASSReviewer 1· 85% conf
The trial design is adequately described, including randomization, blinding, and pre-specified inclusion/exclusion criteria, though the trial was terminated early.
Evidence
direct quote[Methods, Trial procedures]
“Randomization was stratified by region and ACEi or ARB versus sacubitril/valsartan background therapy”direct quote[Abstract]
“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]
“Owing to the early study termination, the primary estimand and statistical modeling for the dose–response relationship were no longer applicable.”WARNReviewer 2· 85% conf
The study design is a randomized, partially blinded, parallel-group trial with appropriate stratification, but the early termination and lack of a pre-specified primary analysis plan for the actual sample size limit the rigor.
Evidence
absence[Methods, Trial procedures]
Randomization method is not described in detail.direct quote[Abstract]
“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.”paraphrase[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%.”PASSReviewer 3· 85% conf
The trial design is rigorous with appropriate randomization, blinding, and pre-specified inclusion/exclusion criteria, though the power analysis was not met due to early termination.
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]
“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]
“a sample size of 600 participants (120 allocated to placebo, 120 to 60 mg of XXB750, 180 to 120 mg of XXB750 and 180 to 240 mg of XXB750) would have provided a power of 90% if the underlying true maximum NT-proBNP reduction with XXB750 versus placebo was 23%.”