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

Stroke Clinical Trial

— PROMOTE  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05155137
• Other study ID #: 41456820.6.1001.5330
• Status: Recruiting
• Phase: Phase 3
• Start date: December 20, 2021
• Est. completion date: December 14, 2026

Study information

• Verified date: January 2023
• Source: Hospital Moinhos de Vento
• Contact: Sheila CO Martins, PhD
• Phone: 5551999628467
• Email: sheila[@]redebrasilavc.org.br
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 12268
• Est. completion date: December 14, 2026
• Est. primary completion date: December 14, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Cognitive Decline
• Cognitive Dysfunction
• Stroke

Intervention

Drug:
• Drug Capsule (Valsartan + Amlodipine + Rosuvastatin)
Polypill with 3 medications (Valsartan 80 mg + Amlodipine 5 mg + Rosuvastatin 10 mg)

Behavioral:
• Stroke Riskometer
the primary care units will be randomized to use Stroke Riskometer App together with health community workers to help in the lifestyle modifications

Locations

Country	Name	City	State
Brazil	Unidade de Saúde Santa Cecília	Porto Alegre	Rio Grande Do Sul

Sponsors (3)

Lead Sponsor	Collaborator
Hospital Moinhos de Vento	Ministry of Health, Brazil, World Stroke Organization

Country where clinical trial is conducted

Brazil, 

References & Publications (16)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. Erratum In: JAMA. 2017 Feb 14;317(6):648. — View Citation

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. — View Citation

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. Stroke. 2018 Nov 21:STROKEAHA118023058. doi: 10.1161/STROKEAHA.118.023058. Online ahead of print. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. Erratum In: N Engl J Med. 2018 Oct 11;379(15):1486. — View Citation

* Note: There are 16 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Stroke	Incidence of Ischemic or hemorragic stroke	3 years
Primary	Cognitive decline	Cognitive decline rate	3 years
Secondary	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
Secondary	Life Simple Seven Score (LS7)	Diference of LS7 at the baseline and in 3 years comparing the 4 groups	3 years
Secondary	Systolic blood pressure	Systolic blood pressure in 3 years comparing the 4 groups	3 years
Secondary	Cholesterol	Total and LDL cholesterol in 3 years comparing the 4 groups	3 years
Secondary	Numbers of Cardiovascular risk factores	Numbers of Cardiovascular risk factors in the riskometer group comparing to the usual care	3 years
Secondary	Knowledge about risk factors	number of known risk factors comparing riskometer and usual care	3 years
Secondary	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
Secondary	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
Secondary	Cost of stroke treatment	Cost of primary care in the primary care unit	3 years

External Links

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