Polypill and RiscOMeter to Prevent StrOke and CogniTive ImpairmEnt (PROMOTE)

Phase 3

Recruiting

• Conditions: Stroke; Cognitive Decline
• Interventions: Drug: Drug Capsule (Valsartan + Amlodipine + Rosuvastatin); Behavioral: Stroke Riskometer

• Registration Number: NCT05155137
• Lead Sponsor: Hospital Moinhos de Vento

Brief Summary

This study is a phase III, prospective, placebo-controlled randomized clinical trial involving 8,518 subjects with low to moderate stroke risk, followed for 3 years in Brazil. Participants will be randomized to receive either the polypill (valsartan 80 mg, amlodipine 5 mg, and rosuvastatin 10 mg), with dose adjustment of amlodipine to 2.5 mg for patients experiencing adverse events, or a placebo, and to either use the Stroke Riskometer for lifestyle modification or receive usual care. The purpose of the study is to test whether the polypill, alone or in combination with lifestyle modification, will reduce the incidence of stroke and cognitive impairment in this population.

Detailed Description

Background and Aims The increasing burden of stroke and dementia provides strong evidence that current primary prevention strategies are insufficient, as 80% of strokes occur in individuals with low to moderate risk. The purpose of this study is to test whether a polypill, used alone or in combination with lifestyle modification, will reduce the incidence of stroke and cognitive impairment in a population with low to moderate stroke risk.

Methods

This is a phase III, multicenter, prospective, double-blind, placebo-controlled randomized clinical trial of 8,518 subjects with low to moderate stroke risk, followed for 3 years. The study will include 80 Health Units affiliated with 20 research centers in Brazil. After a run-in phase (30 days, all participants with active drug), participants will be randomized to receive either the polypill (valsartan 80 mg, amlodipine 5 mg, and rosuvastatin 10 mg) or a placebo (with dose adjustment of amlodipine to 2.5 mg for patients experiencing adverse events), and to either use the Stroke Riskometer for lifestyle modification or receive usual care. It will be included: (1)adults aged 50-75 years; (2) no previous history of stroke, TIA or cardiovascular disease; (3)systolic blood pressure (BP) 121-139 mmHg; (4) one or more lifestyle risk factors (smoking, overweight, physical inactivity or inadequate diet. It will be excluded patients with hypercholesterolemia or diabetes or take other antihypertensive drugs or open label statins. Subjects will be randomized under a minimization process:

* Age: 50-64 vs 65-75

* Sex: men vs women

* BP: 121-130 vs 131-139

* Education level: \<5 years vs \> 5 years

* Total Cholesterol: \<5 mmol (194 mg/dl) vs \<5 mmol (194 mg/dl)

The study will be conducted in 2 parts:

Part 1. Family Health Strategy Units (10 clusters) located in Porto Alegre will be eligible to participate in part 1, which will assess surrogate endpoints in 370 patients included in the study in 9 months (blood pressure reduction and change in stroke risk by the scale LS7). Also we will evaluate the strategies, and barriers for implementation and adverse events.

Part 2. 80 Family Health Strategy Units, affiliated with 20 research centers, in the 5 Brazilian regions, 8,518 participants followed for 3 years measuring stroke incidence and cognitive decline rate as the primary outcome. Expected results in primary outcome: to reduce the incidence of stroke and cognitive decline in the group of polypill and / or polypill + Riskometer. Secondary outcome: to reduce stroke, MI and cardiovascular death.

Study Timeline

• Study First Submitted: 2021-11-30
• Study First Submitted QC: 2021-12-10
• Study First Posted: 2021-12-13
• Study Start: 2021-12-20
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-20
• Last Update Posted: 2025-01-23
• Primary Completion: 2029-12-14
• Study Completion: 2030-12-14

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 8518

Inclusion Criteria

• adults aged 50-75 years;
• no previous history of stroke, TIA or cardiovascular disease;
• systolic blood pressure (SBP) 121-139 mmHg;
• with one or more lifestyle risk factors: smoking, overweight (BMI> 25 kg / m2), physical inactivity (WHO criteria for aerobic physical activity <150 minutes / week or at least 75 minutes of aerobic physical activity of vigorous intensity during the week or an equivalent combination of activity of moderate and vigorous intensity) or inadequate diet / poor eating habits (low intake of fruits and vegetables, fish, whole grains, high intake of drinks sweetened with sodium and sugar)
• owns or has access to a cell phone that can receive text messages.

Exclusion Criteria

• Diagnostic of hypercholesterolemia (> 190mg/dL LDL cholesterol) or diabetes or take other antihypertensive drugs or open label statins;
• Contraindication to the medication
• Life expectancy < 5 years
• Participation in another clinical trial

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Polypill + Stroke Riskometer	Drug Capsule (Valsartan + Amlodipine + Rosuvastatin)	Participants will be randomized to use the active polypill (valsartan 80 mg, amlodipine 5 mg, and rosuvastatin 10 mg) and to use the Stroke Riskometer for lifestyle modification
Polypill + Stroke Riskometer	Stroke Riskometer	Participants will be randomized to use the active polypill (valsartan 80 mg, amlodipine 5 mg, and rosuvastatin 10 mg) and to use the Stroke Riskometer for lifestyle modification
Placebo + Stroke Riskometer	Stroke Riskometer	Participants will be randomized to use placebo polypill and to use the Stroke Riskometer for lifestyle modification
Polypill + No Stroke Riskometer (Usual care)	Drug Capsule (Valsartan + Amlodipine + Rosuvastatin)	Participants will be randomized to use the active polypill (valsartan 80 mg, amlodipine 5 mg, and rosuvastatin 10 mg) and will not use the Stroke Riskometer

Primary Outcome Measures

Name	Time	Method
Stroke	3 years	Incidence of Ischemic or hemorrhagic stroke
Cognitive decline	3 years	Cognitive decline rate

Secondary Outcome Measures

Name	Time	Method
MACE	3 years	Incidence of Stroke/TIA, Myocardial infarction, hospitalization for cardiovascular cause and cardiovascular death comparing the polypill and placebo group and comparing riskometer and no riskometer group
Life's Essential 8 Score (LE8)	3 years	Proportion of participants with decreased risk for LE8 comparing the 4 groups. The score range from 0 to 100 with higher scores indicating better cardiovascular health
Systolic blood pressure	3 years	Systolic blood pressure in 3 years comparing the 4 groups
Cholesterol	3 years	Total and LDL cholesterol in 3 years comparing the 4 groups
Numbers of Cardiovascular risk factors	3 years	Numbers of Cardiovascular risk factors in the riskometer group comparing to the usual care
Quality of Life Analysis	3 years	Quality of life analysis as measured by EuroQol/EQ5D comparing the 4 groups. The score range from 0.33 to 1 with higher scores indicating better quality if life
Cost of stroke treatment	3 years	Cost of primary care in the primary care unit

Trial Locations

Locations (2)

Unidade de Saúde Santa Cecília / Hospital de Clínicas de Porto Alegre; 🇧🇷 Porto Alegre, Rio Grande Do Sul, Brazil

Hospital Moinhos de Vento; 🇧🇷 Porto Alegre, Rio Grande Do Sul, Brazil