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

NCT05155137 | Recruiting Phase 3 DMC

• 1 other identifier: 41456820.6.1001.5330
• Study Type: interventional
• Target: 8,518
• Locations: 1 country
• Sites: 2

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.

Conditions

Stroke; Cognitive Decline

Keywords

stroke; cognitive decline; prevention; polypill; stroke riskometer; primary care

Outcome Measures

Primary Outcomes (2)

• Stroke

  Incidence of Ischemic or hemorrhagic stroke

  3 years

• Cognitive decline

  Cognitive decline rate

  3 years

Secondary Outcomes (8)

• MACE

  3 years

• Life's Essential 8 Score (LE8)

  3 years

• Systolic blood pressure

  3 years

• Cholesterol

  3 years

• Numbers of Cardiovascular risk factors

  3 years

Study Arms (4)

Polypill + Stroke Riskometer

EXPERIMENTAL

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

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

Placebo + Stroke Riskometer

PLACEBO COMPARATOR

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

Behavioral: Stroke Riskometer

Polypill + No Stroke Riskometer (Usual care)

EXPERIMENTAL

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

Drug: Drug Capsule (Valsartan + Amlodipine + Rosuvastatin)

Placebo + No Riskometer (Usual Care)

NO INTERVENTION

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

Interventions

Drug Capsule (Valsartan + Amlodipine + Rosuvastatin) DRUG

Polypill with 3 medications (Valsartan 80 mg + Amlodipine 5 mg + Rosuvastatin 10 mg)

Polypill + No Stroke Riskometer (Usual care); Polypill + Stroke Riskometer

Stroke Riskometer BEHAVIORAL

Participants will be randomized to use Stroke Riskometer App for lifestyle modifications

Placebo + Stroke Riskometer; Polypill + Stroke Riskometer

Eligibility Criteria

• Age: 50 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Hospital Moinhos de Vento: lead
• Ministry of Health, Brazil: collaborator
• World Stroke Organization: collaborator

Study Sites (2)

Unidade de Saúde Santa Cecília / Hospital de Clínicas de Porto Alegre

Porto Alegre, Rio Grande do Sul, 90620-110, Brazil

RECRUITING

Hospital Moinhos de Vento

Porto Alegre, Rio Grande do Sul, Brazil

RECRUITING

Related Publications (16)

• 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 BACKGROUND

• 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 Neurol. 2016 Aug;15(9):913-924. doi: 10.1016/S1474-4422(16)30073-4. Epub 2016 Jun 9.

  PMID: 27291521 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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, Lotufo PA, Malekzadeh R, Melaku YA, Mensah GA, Misganaw A, Mokdad AH, Moran AE, Nawaz H, Neal B, Ngalesoni FN, Ohkubo T, Pourmalek F, Rafay A, Rai RK, Rojas-Rueda D, Sampson UK, Santos IS, Sawhney M, Schutte AE, Sepanlou SG, Shifa GT, Shiue I, Tedla BA, Thrift AG, Tonelli M, Truelsen T, Tsilimparis N, Ukwaja KN, Uthman OA, Vasankari T, Venketasubramanian N, Vlassov VV, Vos T, Westerman R, Yan LL, Yano Y, Yonemoto N, Zaki ME, Murray CJ. Global Burden of Hypertension and Systolic Blood Pressure of at Least 110 to 115 mm Hg, 1990-2015. JAMA. 2017 Jan 10;317(2):165-182. doi: 10.1001/jama.2016.19043.

  PMID: 28097354 BACKGROUND

• 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 3.0 million participants. Lancet. 2011 Feb 12;377(9765):578-86. doi: 10.1016/S0140-6736(10)62038-7. Epub 2011 Feb 3.

  PMID: 21295847 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• Yusuf S, Lonn E, Pais P, Bosch J, Lopez-Jaramillo P, Zhu J, Xavier D, Avezum A, Leiter LA, Piegas LS, Parkhomenko A, Keltai M, Keltai K, Sliwa K, Chazova I, Peters RJ, Held C, Yusoff K, Lewis BS, Jansky P, Khunti K, Toff WD, Reid CM, Varigos J, Accini JL, McKelvie R, Pogue J, Jung H, Liu L, Diaz R, Dans A, Dagenais G; HOPE-3 Investigators. Blood-Pressure and Cholesterol Lowering in Persons without Cardiovascular Disease. N Engl J Med. 2016 May 26;374(21):2032-43. doi: 10.1056/NEJMoa1600177. Epub 2016 Apr 2.

  PMID: 27039945 BACKGROUND

• Brainin M, Feigin V, Martins S, Matz K, Roy J, Sandercock P, Teuschl Y, Tuomilehto J, Wiseman A. Cut stroke in half: Polypill for primary prevention in stroke. Int J Stroke. 2018 Aug;13(6):633-647. doi: 10.1177/1747493018761190. Epub 2018 Feb 20.

  PMID: 29461155 BACKGROUND

• Elley CR, Gupta AK, Webster R, Selak V, Jun M, Patel A, Rodgers A, Thom S. The efficacy and tolerability of 'polypills': meta-analysis of randomised controlled trials. PLoS One. 2012;7(12):e52145. doi: 10.1371/journal.pone.0052145. Epub 2012 Dec 19.

  PMID: 23284906 BACKGROUND

• Roshandel G, Khoshnia M, Poustchi H, Hemming K, Kamangar F, Gharavi A, Ostovaneh MR, Nateghi A, Majed M, Navabakhsh B, Merat S, Pourshams A, Nalini M, Malekzadeh F, Sadeghi M, Mohammadifard N, Sarrafzadegan N, Naemi-Tabiei M, Fazel A, Brennan P, Etemadi A, Boffetta P, Thomas N, Marshall T, Cheng KK, Malekzadeh R. Effectiveness of polypill for primary and secondary prevention of cardiovascular diseases (PolyIran): a pragmatic, cluster-randomised trial. Lancet. 2019 Aug 24;394(10199):672-683. doi: 10.1016/S0140-6736(19)31791-X.

  PMID: 31448738 BACKGROUND

• Sung J, Jeong JO, Kwon SU, Won KH, Kim BJ, Cho BR, Kim MK, Lee S, Kim HJ, Lim SH, Park SW, Park JE. Valsartan 160 mg/Amlodipine 5 mg Combination Therapy versus Amlodipine 10 mg in Hypertensive Patients with Inadequate Response to Amlodipine 5 mg Monotherapy. Korean Circ J. 2016 Mar;46(2):222-8. doi: 10.4070/kcj.2016.46.2.222. Epub 2016 Mar 21.

  PMID: 27014353 BACKGROUND

• Brainin M, Feigin V, Bath PM, Collantes E, Martins S, Pandian J, Sacco R, Teuschl Y. Multi-level community interventions for primary stroke prevention: A conceptual approach by the World Stroke Organization. Int J Stroke. 2019 Oct;14(8):818-825. doi: 10.1177/1747493019873706. Epub 2019 Sep 9.

  PMID: 31500553 BACKGROUND

• Parmar P, Krishnamurthi R, Ikram MA, Hofman A, Mirza SS, Varakin Y, Kravchenko M, Piradov M, Thrift AG, Norrving B, Wang W, Mandal DK, Barker-Collo S, Sahathevan R, Davis S, Saposnik G, Kivipelto M, Sindi S, Bornstein NM, Giroud M, Bejot Y, Brainin M, Poulton R, Narayan KM, Correia M, Freire A, Kokubo Y, Wiebers D, Mensah G, BinDhim NF, Barber PA, Pandian JD, Hankey GJ, Mehndiratta MM, Azhagammal S, Ibrahim NM, Abbott M, Rush E, Hume P, Hussein T, Bhattacharjee R, Purohit M, Feigin VL; Stroke RiskometerTM Collaboration Writing Group. The Stroke Riskometer(TM) App: validation of a data collection tool and stroke risk predictor. Int J Stroke. 2015 Feb;10(2):231-44. doi: 10.1111/ijs.12411. Epub 2014 Dec 10.

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• Krishnamurthi R, Hale L, Barker-Collo S, Theadom A, Bhattacharjee R, George A, Arroll B, Ranta A, Waters D, Wilson D, Sandiford P, Gall S, Parmar P, Bennett D, Feigin V. Mobile Technology for Primary Stroke Prevention: A Proof-of-Concept Pilot Randomized Controlled Trial. Stroke. 2019 Jan;50(1):196-198. doi: 10.1161/STROKEAHA.118.023058. Epub 2018 Nov 21.

  PMID: 30580699 BACKGROUND

Related Links

• The HEARTS technical package provides a strategic approach to improving cardiovascular health in countries. It comprises six modules and an implementation guide

MeSH Terms

Conditions

Stroke; Cognitive Dysfunction

Interventions

Pharmaceutical Preparations; Valsartan; Amlodipine; Rosuvastatin Calcium

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Tetrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Valine; Amino Acids, Branched-Chain; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Essential; Dihydropyridines; Pyridines; Sulfonamides; Amides; Organic Chemicals; Fluorobenzenes; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrimidines

Study Officials

• Sheila CO Martins, PhD

  Hospital Moinhos de Vento

  PRINCIPAL INVESTIGATOR

• Michael Brainin, MD

  Danube University Krems, Austria

  STUDY CHAIR

• Valery Feigin, PhD

  AUT University, Oakland, New Zealand

  STUDY CHAIR

• Thais L Secchi, MSc

  Hospital Moinhos de Vento

  STUDY DIRECTOR

Central Study Contacts

Sheila CO Martins, PhD

CONTACT

5551999628467; sheila@redebrasilavc.org.br

Thais L Secchi, MSc

CONTACT

5551998977789; thais.secchi@hmv.org.br

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Investigator and patient will be blinded for polypill or placebo and the outcomes evaluator will be blinded for the treatment
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: November 30, 2021
• First Posted: December 13, 2021
• Study Start: December 20, 2021
• Primary Completion (Estimated): December 14, 2029
• Study Completion (Estimated): December 14, 2030
• Last Updated: January 23, 2025

Record last verified: 2025-01

Locations

BR (2)