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

Overview

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.

Interventions

• Drug Drug Capsule (Valsartan + Amlodipine + Rosuvastatin)
  Polypill with 3 medications (Valsartan 80 mg + Amlodipine 5 mg + Rosuvastatin 10 mg)
• Behavioral Stroke Riskometer
  Participants will be randomized to use Stroke Riskometer App for lifestyle modifications

Primary outcome measures

• Stroke [Time frame: 3 years]
• Cognitive decline [Time frame: 3 years]

Secondary outcome measures (8)

• MACE [Time frame: 3 years]
• Life's Essential 8 Score (LE8) [Time frame: 3 years]
• Systolic blood pressure [Time frame: 3 years]
• Cholesterol [Time frame: 3 years]
• Numbers of Cardiovascular risk factors [Time frame: 3 years]
• Quality of Life Analysis [Time frame: 3 years]
• Life's Essential 8 Score (LE8) [Time frame: 3 years]
• Cost of stroke treatment [Time frame: 3 years]

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Prevention

Study locations

Brazil · 2 centers

• Unidade de Saúde Santa Cecília / Hospital de Clínicas de Porto Alegre — Porto Alegre
• Hospital Moinhos de Vento — Porto Alegre

Publications

• GBD 2015 Neurological Disorders Collaborator Group. Global, regional, and national burden of neurological disorders during 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet Neurol. 2017 Nov;16(11):877-897. doi: 10.1016/S1474-4422(17)30299-5. Epub 2017 Sep 17. PMID 28931491
• Feigin VL, Roth GA, Naghavi M, Parmar P, Krishnamurthi R, Chugh S, Mensah GA, Norrving B, Shiue I, Ng M, Estep K, Cercy K, Murray CJL, Forouzanfar MH; Global Burden of Diseases, Injuries and Risk Factors Study 2013 and Stroke Experts Writing Group. Global burden of stroke and risk factors in 188 countries, during 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet PMID 27291521
• The Lancet Neurology. The shared burden of stroke and dementia. Lancet Neurol. 2016 Aug;15(9):891. doi: 10.1016/S1474-4422(16)30132-6. No abstract available. PMID 27478943
• Feigin VL, Norrving B, George MG, Foltz JL, Roth GA, Mensah GA. Prevention of stroke: a strategic global imperative. Nat Rev Neurol. 2016 Sep;12(9):501-12. doi: 10.1038/nrneurol.2016.107. Epub 2016 Jul 22. PMID 27448185
• Forouzanfar MH, Liu P, Roth GA, Ng M, Biryukov S, Marczak L, Alexander L, Estep K, Hassen Abate K, Akinyemiju TF, Ali R, Alvis-Guzman N, Azzopardi P, Banerjee A, Barnighausen T, Basu A, Bekele T, Bennett DA, Biadgilign S, Catala-Lopez F, Feigin VL, Fernandes JC, Fischer F, Gebru AA, Gona P, Gupta R, Hankey GJ, Jonas JB, Judd SE, Khang YH, Khosravi A, Kim YJ, Kimokoti RW, Kokubo Y, Kolte D, Lopez A PMID 28097354
• Farzadfar F, Finucane MM, Danaei G, Pelizzari PM, Cowan MJ, Paciorek CJ, Singh GM, Lin JK, Stevens GA, Riley LM, Ezzati M; Global Burden of Metabolic Risk Factors of Chronic Diseases Collaborating Group (Cholesterol). National, regional, and global trends in serum total cholesterol since 1980: systematic analysis of health examination surveys and epidemiological studies with 321 country-years and PMID 21295847
• O'Regan C, Wu P, Arora P, Perri D, Mills EJ. Statin therapy in stroke prevention: a meta-analysis involving 121,000 patients. Am J Med. 2008 Jan;121(1):24-33. doi: 10.1016/j.amjmed.2007.06.033. PMID 18187070
• Feigin VL, Norrving B, Mensah GA. Primary prevention of cardiovascular disease through population-wide motivational strategies: insights from using smartphones in stroke prevention. BMJ Glob Health. 2017 Apr 4;2(2):e000306. doi: 10.1136/bmjgh-2017-000306. eCollection 2016. PMID 28589034

Identifiers

NCT: NCT05155137 · 41456820.6.1001.5330

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗