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

Hospital Moinhos de Vento

Status and phase: Enrolling; Phase 3

Conditions: Stroke; Cognitive Decline

Treatments: Drug: Drug Capsule (Valsartan + Amlodipine + Rosuvastatin); Behavioral: Stroke Riskometer

Study type: Interventional

Funder types: Other

Identifiers

NCT05155137

41456820.6.1001.5330

Details and patient eligibility

About

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.

Full 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.

Enrollment: 8,518 estimated patients

Sex: All

Ages: 50 to 75 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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8,518 participants in 4 patient groups, including a placebo group

Polypill + Stroke Riskometer

Experimental group

Description:

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

Treatment:

Behavioral: Stroke Riskometer

Drug: Drug Capsule (Valsartan + Amlodipine + Rosuvastatin)

Placebo + Stroke Riskometer

Placebo Comparator group

Description:

Participants will be randomized to use placebo polypill and to use the Stroke Riskometer for lifestyle modification

Treatment:

Behavioral: Stroke Riskometer

Polypill + No Stroke Riskometer (Usual care)

Experimental group

Description:

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

Treatment:

Drug: Drug Capsule (Valsartan + Amlodipine + Rosuvastatin)

Placebo + No Riskometer (Usual Care)

No Intervention group

Description:

Participants will be randomized to use placebo polypill and will not use the Stroke Riskometer