Polypill and Riskometer to Prevent Stroke and Cognitive Impairment in Primary Health Care (PROMOTE) Randomized Clinical Trial: Rationale and Design

Sheila Ouriques Martins^{1

2}, Michael Brainin³, Craig S Anderson^{4

5}, Philip M Bath⁶, Graeme J Hankey^{7

8}, Renato D Lopes⁹, Otávio Berwanger¹⁰, Luciano A Sposato¹¹, Aline Palmeira Pires¹², Thaís Leite Secchi¹², Brunna Jaeger Teló¹², Franciele P Santos¹², Jaqueline Radin¹², Juliana Ellwanger¹², Magda Ouriques Martins¹², Danielle A Pereira¹², Francine W Quadros¹², Larissa Vitoria Silva¹³, Marcelo Rodrigues Gonçalves¹⁴, Gabriel Paulo Mantovani¹, Manoela Ceretta¹³, João Eduardo Bastianello¹³, Arthur Pille¹, Guilherme B Andrade¹², Caroline Schirmer¹⁵, Octávio Marques Pontes-Neto¹⁶, Gisele Sampaio Silva¹⁷, Luiz Antonio Nasi¹⁸, Aline R Zimmer¹⁹, Diogo O Souza¹⁹, Eduardo R Zimmer¹⁹, Márcio Rodrigues²⁰, Maicon Falavigna²¹, Valery L Feigin²²; World Stroke Organization’s Cut Stroke in Half Project

Affiliations

¹ Neurology, Hospital Moinhos de Vento, Universidade Federal do Rio Grande do Sul, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
² World Stroke Organization, Geneva, Switzerland.
³ Department of Clinical Neurosciences and Preventive Medicine, Danube University, Krems an der Donau, Austria.
⁴ The George Institute for Global Health, University of New South Wales, Sydney, New South Wales, Australia.
⁵ Institute of Science and Technology for Brain-inspired Intelligence, Fudan University, Shanghai, China.
⁶ Stroke Trials Unit, University of Nottingham, Nottingham, UK.
⁷ Centre for Neuromuscular and Neurological Disorders, Medical School, The University of Western Australia, Perth, Washington, Australia.
⁸ The Perron Institute for Neurological and Translational Science, Perth, Washington, Australia.
⁹ Duke University Medical Center, Durham, North Carolina, USA.
¹⁰ Imperial College London, and The George Institute for Global Health UK, London, UK.
¹¹ Western University Schulich School of Medicine and Dentistry, London, Ontario, Canada.
¹² Neurology, Hospital Moinhos de Vento, Porto Alegre, Brazil.
¹³ Neurology, Universidade Federal do Rio Grande do Sul, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
¹⁴ Family and Community Medicine, Universidade Federal do Rio Grande do Sul, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
¹⁵ Primary Health Care Department, Municipal Secretary of Health of Porto Alegre, Porto Alegre, Brazil.
¹⁶ Neurology Service, Ribeirão Preto Medical School University of Sao Paulo, Ribeirao Preto, Brazil.
¹⁷ Vascular Neurology and Intensive Care, Universidade Federal de São Paulo, São Paulo, Brazil.
¹⁸ Hospital Moinhos de Vento, and Universidade Federal do Rio Grande do Sul, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
¹⁹ Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
²⁰ Hospital de Clinicas de Porto Alegre, and Primary Health Care Department, Municipal Secretary of Health of Porto Alegre, Porto Alegre, Brazil.
²¹ Hospital Moinhos de Vento, National Institute for Health Technology Assessment, Universidade Federal do Rio Grande do Sul, and Research Unit, Inova Medical, Porto Alegre, Brazil.
²² National Institute for Stroke and Applied Neurosciences, Auckland University of Technology, Auckland, New Zealand.

PMID: 40875725
DOI: 10.1159/000547359

Polypill and Riskometer to Prevent Stroke and Cognitive Impairment in Primary Health Care (PROMOTE) Randomized Clinical Trial: Rationale and Design

Sheila Ouriques Martins et al. Neuroepidemiology. 2025.

. 2025 Aug 23:1-9.

doi: 10.1159/000547359. Online ahead of print.

Authors

Affiliations

¹ Neurology, Hospital Moinhos de Vento, Universidade Federal do Rio Grande do Sul, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
² World Stroke Organization, Geneva, Switzerland.
³ Department of Clinical Neurosciences and Preventive Medicine, Danube University, Krems an der Donau, Austria.
⁴ The George Institute for Global Health, University of New South Wales, Sydney, New South Wales, Australia.
⁵ Institute of Science and Technology for Brain-inspired Intelligence, Fudan University, Shanghai, China.
⁶ Stroke Trials Unit, University of Nottingham, Nottingham, UK.
⁷ Centre for Neuromuscular and Neurological Disorders, Medical School, The University of Western Australia, Perth, Washington, Australia.
⁸ The Perron Institute for Neurological and Translational Science, Perth, Washington, Australia.
⁹ Duke University Medical Center, Durham, North Carolina, USA.
¹⁰ Imperial College London, and The George Institute for Global Health UK, London, UK.
¹¹ Western University Schulich School of Medicine and Dentistry, London, Ontario, Canada.
¹² Neurology, Hospital Moinhos de Vento, Porto Alegre, Brazil.
¹³ Neurology, Universidade Federal do Rio Grande do Sul, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
¹⁴ Family and Community Medicine, Universidade Federal do Rio Grande do Sul, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
¹⁵ Primary Health Care Department, Municipal Secretary of Health of Porto Alegre, Porto Alegre, Brazil.
¹⁶ Neurology Service, Ribeirão Preto Medical School University of Sao Paulo, Ribeirao Preto, Brazil.
¹⁷ Vascular Neurology and Intensive Care, Universidade Federal de São Paulo, São Paulo, Brazil.
¹⁸ Hospital Moinhos de Vento, and Universidade Federal do Rio Grande do Sul, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
¹⁹ Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
²⁰ Hospital de Clinicas de Porto Alegre, and Primary Health Care Department, Municipal Secretary of Health of Porto Alegre, Porto Alegre, Brazil.
²¹ Hospital Moinhos de Vento, National Institute for Health Technology Assessment, Universidade Federal do Rio Grande do Sul, and Research Unit, Inova Medical, Porto Alegre, Brazil.
²² National Institute for Stroke and Applied Neurosciences, Auckland University of Technology, Auckland, New Zealand.

PMID: 40875725
DOI: 10.1159/000547359

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 80 mg, amlodipine 5 mg, and rosuvastatin 10 mg), 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: A 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 mm Hg 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's 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-mm Hg (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 behavioural 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.

Keywords: Clinical trials; Dementia; Hypertension; Lifestyle risk; Polypill; Prevention; Stroke.

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Polypill and Riskometer to Prevent Stroke and Cognitive Impairment in Primary Health Care (PROMOTE) Randomized Clinical Trial: Rationale and Design

Affiliations

Polypill and Riskometer to Prevent Stroke and Cognitive Impairment in Primary Health Care (PROMOTE) Randomized Clinical Trial: Rationale and Design

Authors

Affiliations

Abstract

LinkOut - more resources

Full Text Sources

Miscellaneous