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

Phase 3

Recruiting

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

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

Brief Summary

This study is a phase III Randomized Clinical Trial, prospective, placebo controlled of 12,268 subjects with low to moderate risk of stroke followed by 3 years in 60 Primary Health Care Units in Brazil. The units will be randomized (clusters) to use or not the approach of community health workers with the Stroke Riskometer. After, patients will be randomized to receive the polypill (valsartan 80 mg, amlodipine 5 mg and rosuvastatin 10 mg) or placebo (dose adjustment of amlodipine 2,5 for patients with adverse events). The purpose is to test whether a 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 increase burden of stroke and dementia provides strong evidence that currently used primary prevention strategies are not enough and 80% of strokes occur in people with low to moderate risk. The purpose 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 of individuals with low to moderate risk of stroke.

Methods

Phase III Randomized Clinical Trial, prospective, placebo controlled of 12,268 subjects followed by 3 years. 60 Health Units in Brazil will be randomized (clusters) to use or not the approach of community health workers with the Stroke Riskometer. After a run-in phase (30 days, all participants with active drug), patients will be randomized to receive the polypill (valsartan 80 mg, amlodipine 5 mg and rosuvastatin 10 mg) or placebo (dose adjustment of amlodipine 2,5 for patients with adverse events). 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:

Minimization factors:

* 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. 10 Family Health Strategy Units (10 clusters) located in Porto Alegre will be eligible to participate in part 1, which will assess surrogate endpoints in 1000 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. 60 Family Health Strategy Units in the 5 Brazilian regions, 12,268 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. The results of the first part will be used to review the sample size.

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: 2023-01
• Last Update Submitted: 2023-01-17
• Last Update Posted: 2023-01-18
• Primary Completion: 2025-12-14
• Study Completion: 2026-12-14

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 12268

Inclusion Criteria

• adultos 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 (including CHW) that can receive text messages.

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Exclusion Criteria

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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Riskometer + Placebo	Stroke Riskometer	the unit (cluster) will use the stroke riskometer and the patients will be randomized to use placebo polypill
No Riskometer + Polypill	Drug Capsule (Valsartan + Amlodipine + Rosuvastatin)	the unit (cluster) will not use the stroke riskometer and the patients will be randomized to use the active polypill (valsartan 80 + amlodipine 5 + rosuvastatin 10)
Riskometer + Polypill	Drug Capsule (Valsartan + Amlodipine + Rosuvastatin)	the unit (cluster) will use the stroke riskometer and the patients will be randomized to use the active polypill (valsartan 80 + amlodipine 5 + rosuvastatin 10)
Riskometer + Polypill	Stroke Riskometer	the unit (cluster) will use the stroke riskometer and the patients will be randomized to use the active polypill (valsartan 80 + amlodipine 5 + rosuvastatin 10)

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
MACE	3 years	Incidence of Stroke/TIA, Miocardial infaction, hospitalization for cardiovascular cause and cardiovascular death comparing the polypill and placebo group and comparing riskometer and no riskometer group
Life Simple Seven Score (LS7)	3 years	Diference of LS7 at the baseline and in 3 years comparing the 4 groups
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 factores	3 years	Numbers of Cardiovascular risk factors in the riskometer group comparing to the usual care
Knowledge about risk factors	3 years	number of known risk factors comparing riskometer and 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
Life Simple Seven (LS7) Score	3 years	proportion of participants with decreased risk for LS7 comparing the 4 groups. The score range from 0 to 14 with higher scores indicating better cardiovascular health
Cost of stroke treatment	3 years	Cost of primary care in the primary care unit

Trial Locations

Locations (1)

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