Polypill and RiskOMeter to Prevent StrOke and CogniTive ImpairmEnt in Primary Health Care (PROMOTE) Randomized Clinical Trial: Rationale and Design

Abstract

INTRODUCTION: Stroke and dementia have common modifiable risk factors. Current prevention strategies primarily focus on high-risk populations, leaving a gap in addressing the broader population. We report the protocol for a randomized controlled trial (RCT) that aims to evaluate the feasibility, tolerability, and effectiveness of a polypill (valsartan 80mg, amlodipine 5mg, and rosuvastatin 10mg), with and without use of the Stroke Riskometer app, on systolic blood pressure (SBP) and other cardiovascular disease (CVD) risk factors at 9 months after randomization in a population of low to borderline CVD risk. METHODS: Prospective, pragmatic, multicentre, factorial, phase III, placebo-controlled, cluster RCT in low to moderate CVD risk (10-year risk <20%) individuals aged 50-75 years with no prior history of hypertension, diabetes mellitus, stroke, or other CVD, with a SBP of 121-139 mmHg and at least one lifestyle-related CVD risk factor. Primary Care Units in Porto Alegre, Brazil, were centrally randomized to either use of the Stroke Riskometer app or standard care for lifestyle modification. All eligible individuals underwent a 28-day open run-in phase using the active medication. Participants who tolerated and had high adherence were randomized to either polypill or placebo, using a minimization process according to age, sex, SBP, cholesterol, and education level. The dual primary outcomes were change in SBP and Life Simple 7 (LS7) score at 9 months post-randomization. A sample of 354 participants was estimated to provide 80% statistical power (two sided α=0.05, β =0.20) for 6 clusters with intra-cluster correlation of 0.01 to detect a clinically significant 2.5 mmHg (SD±8) difference in SBP change and 0.65 points (SD±1.61) difference in the LS7 score at 9 months post-randomization between the polypill/Stroke Riskometer group and placebo/usual care group, assuming 10% lost to follow-up. All analyses were conducted according to the intention-to-treat principle. Regression analysis models (ANCOVA) assessed the differences among the four groups concerning changes in SBP, cholesterol levels, cognitive function, and behavioral risk factors over time. CONCLUSION: The findings will provide critical information to allow the development of primary stroke and CVD prevention strategies in low to borderline CVD risk adults. The trial is registered at clinicaltrials.gov NCT05155137.