Clinical trial NCT05155137: Polypill and RiscOMeter to Prevent StrOke and CogniTive ImpairmEnt (PROMOTE)
Official title: Polypill and RiscOMeter to Prevent StrOke and CogniTive ImpairmEnt in Primary Health Care
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Stroke
Cognitive Decline
Keywords: stroke
cognitive decline
prevention
polypill
stroke riskometer
primary care
Lead sponsor: Hospital Moinhos de Vento
Sponsor class: OTHER
Collaborators: name: Ministry of Health, Brazil
name: World Stroke Organization
First posted: 2021-12-13
Enrollment: 8518
Sex: ALL
Minimum age (years): 50
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Phase III, prospective, placebo-controlled randomized clinical trial involving 8,518 individuals in 80 Primary Care Health Units. Participants will be randomized into four groups: 1) Polypill (valsartan 80 mg, amlodipine 5 mg, and rosuvastatin 10 mg) + Stroke Riskometer, 2) Placebo + Stroke Riskometer, 3) Polypill + Usual care, and 4) Placebo + Usual care.
Primary purpose: PREVENTION

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.

Eligibility criteria: 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

Primary outcomes:
measure: Stroke
timeFrame: 3 years
measure: Cognitive decline
timeFrame: 3 years
Secondary outcomes:
measure: MACE
timeFrame: 3 years
measure: Life's Essential 8 Score (LE8)
timeFrame: 3 years
measure: Systolic blood pressure
timeFrame: 3 years
measure: Cholesterol
timeFrame: 3 years
measure: Numbers of Cardiovascular risk factors
timeFrame: 3 years
measure: Quality of Life Analysis
timeFrame: 3 years
measure: Life's Essential 8 Score (LE8)
timeFrame: 3 years
measure: Cost of stroke treatment
timeFrame: 3 years
Other outcomes:
Locations:
city: Porto Alegre
country: Brazil
facility: Unidade de Saúde Santa Cecília / Hospital de Clínicas de Porto Alegre
state: Rio Grande Do Sul
city: Porto Alegre
country: Brazil
facility: Hospital Moinhos de Vento
state: Rio Grande Do Sul
Study officials:
affiliation: Hospital Moinhos de Vento
name: Sheila CO Martins, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Danube University Krems, Austria
name: Michael Brainin, MD
role: STUDY_CHAIR
affiliation: AUT University, Oakland, New Zealand
name: Valery Feigin, PhD
role: STUDY_CHAIR
affiliation: Hospital Moinhos de Vento
name: Thais L Secchi, MSc
role: STUDY_DIRECTOR
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