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

Study Overview
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Brief Summary
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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
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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.

Official Title
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Polipill and RiscOMeter to Prevent StrOke and CogniTive ImpairmEnt in Primary Health Care

Conditions
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Stroke, Cognitive Decline

Intervention / Treatment
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* Drug: Drug Capsule (Valsartan + Amlodipine + Rosuvastatin)
* Behavioral: Stroke Riskometer


Participation Criteria
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Eligibility Criteria
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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. 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

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Phase III Randomized Clinical Trial, prospective, placebo controlled. 60 Primary Care Health Units will be randomized (clusters) to use or not the approach of community health workers with the Stroke Riskometer. After the patients will be randomized for polypill (valsartan 80 mg, amlodipine 5 mg e rosuvastatin 10 mg) or placebo
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Riskometer + Polypill<br>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) | Drug: Drug Capsule (Valsartan + Amlodipine + Rosuvastatin)<br>* Polypill with 3 medications (Valsartan 80 mg + Amlodipine 5 mg + Rosuvastatin 10 mg)<br>Behavioral: Stroke Riskometer<br>* the primary care units will be randomized to use Stroke Riskometer App together with health community workers to help in the lifestyle modifications<br>|
| Placebo Comparator: Riskometer + Placebo<br>the unit (cluster) will use the stroke riskometer and the patients will be randomized to use placebo polypill | Behavioral: Stroke Riskometer<br>* the primary care units will be randomized to use Stroke Riskometer App together with health community workers to help in the lifestyle modifications<br>|
| Experimental: No Riskometer + Polypill<br>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) | Drug: Drug Capsule (Valsartan + Amlodipine + Rosuvastatin)<br>* Polypill with 3 medications (Valsartan 80 mg + Amlodipine 5 mg + Rosuvastatin 10 mg)<br>|
| No Intervention: No Riskometer + Placebo (Usual Care)<br>the unit (cluster) will not use the stroke riskometer and the patients will be randomized to use the placebo polypill = usual care | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Stroke | Incidence of Ischemic or hemorragic stroke | 3 years | 
| Cognitive decline | Cognitive decline rate | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MACE | 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 | 3 years | 
| Life Simple Seven Score (LS7) | Diference of LS7 at the baseline and in 3 years comparing the 4 groups | 3 years | 
| Systolic blood pressure | Systolic blood pressure in 3 years comparing the 4 groups | 3 years | 
| Cholesterol | Total and LDL cholesterol in 3 years comparing the 4 groups | 3 years | 
| Numbers of Cardiovascular risk factores | Numbers of Cardiovascular risk factors in the riskometer group comparing to the usual care | 3 years | 
| Knowledge about risk factors | number of known risk factors comparing riskometer and usual care | 3 years | 
| Quality of Life Analysis | 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 | 3 years | 
| Life Simple Seven (LS7) Score | 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 | 3 years | 
| Cost of stroke treatment | Cost of primary care in the primary care unit | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stroke, cognitive decline, prevention, polypill, stroke riskometer, primary care