Polypill and Colchicine for Risk Reduction in Atherosclerotic Cardiovascular Disease

NCT ID: NCT06930885

Last Updated: 2026-01-22

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 7713 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-06-12
• Study Completion Date: 2031-05-31

Brief Summary

The EPOCA study (Evaluation of a POlypill and Colchicine for risk reduction in patients with established Atherosclerotic cardiovascular disease) will be a randomized, superiority, parallel, 2x2 factorial, multicenter clinical trial which will include at least 7713 and up to a maximum of 10797 participants with established atherosclerotic cardiovascular disease.

Detailed Description

Cardiovascular disease is the leading cause of morbidity and mortality worldwide and in Brazil. Additionally, cardiovascular risk factors are highly prevalent conditions which are, frequently, present in association. Despite the last therapeutic advances, rates of adequate control of these conditions are still low. One proposed strategy to increase such control and decrease cardiovascular risk is the use of fixed-dose combinations of different pharmacological classes, to be taken on single daily dose - a polypill. This strategy has already been studied in other parts of the world, especially in patients with established or at risk for coronary heart disease (CHD).

Furthermore, there has been a need to explore other therapeutic targets beyond traditional risk factors that could impact the process of atherosclerosis. Among the various options evaluated, colchicine has emerged as a viable alternative, given its clinical use experience, mechanism of action, and the results showing a reduction in inflammatory biomarkers as well as clinical outcomes in individuals with different manifestations of coronary artery disease. However, it is important to highlight some key points regarding the available studies evaluating both the treatment strategy based on a polypill and the use of colchicine in the context of atherosclerotic cardiovascular disease (ASCVD).

The studies supporting both approaches were primarily conducted with participants with coronary artery disease from centers in Europe, the U.S., Iran, Oceania, and India, and there is a lack of robust evidence regarding these therapeutic strategies in other countries with a diverse population like Brazil, as well as in individuals with other manifestations of ASCVD (including peripheral arterial disease and cerebrovascular disease).

Given high prevalence of atherosclerotic cardiovascular disease and its traditional risk factors, low control rates, high levels of poor adherence and therapeutic inertia, and the specific realities of the population and healthcare system, evaluating the efficacy of a polypill strategy (fixed-dose an antihypertensive, aspirin, and high-potency statin) with a single daily dose, along with colchicine, in preventing cardiovascular events could contribute to improving cardiovascular care.

Conditions

Atherothrombotic Diseases; Atherosclerotic Cardiovascular Disease (ASCVD)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Group 1

Cardiovascular Polypill + Colchicine 0.5 mg once daily

Group Type: EXPERIMENTAL

Cardiovascular Polypill (Valsartan, Atorvastatin, Aspirin)

Intervention Type: DRUG

Cardiovascular Polypill contains Valsartan, Atorvastatin, Aspirin

1. Valsartan 160 mg + Atorvastatin 40 mg + Aspirin 100 mg

or

2. Valsartan 160 mg + Atorvastatin 80 mg + Aspirin 100 mg

or

3. Valsartan 320 mg + Atorvastatin 40 mg + Aspirin 100 mg

or

4. Valsartan 320 mg + Atorvastatin 80 mg + Aspirin100 mg

or

5. Valsartan 80 mg + Atorvastatin 40 mg + Aspirin 100 mg

or

6. Valsartan 80 mg + Atorvastatin 80 mg + Aspirin 100 mg

or

7. Valsartan 80 mg + Atorvastatin 20 mg + Aspirin 100 mg*

or

8. Valsartan 160 mg + Atorvastatin 20 mg + Aspirin 100 mg*

or

9. Valsartan 320 mg + Atorvastatin 20 mg + Aspirin 100 mg*

• The use of these formulations of the cardiovascular polypill will be restricted to cases of Statin-Related Muscle Symptoms (SRMS)

Colchicine 0.5 mg

Intervention Type: DRUG

Colchicine 0.5 mg once daily

Group 2

Cardiovascular Polypill + Colchicine placebo 0.5 mg once daily

Group Type: EXPERIMENTAL

Cardiovascular Polypill (Valsartan, Atorvastatin, Aspirin)

Intervention Type: DRUG

Cardiovascular Polypill contains Valsartan, Atorvastatin, Aspirin

1. Valsartan 160 mg + Atorvastatin 40 mg + Aspirin 100 mg

or

2. Valsartan 160 mg + Atorvastatin 80 mg + Aspirin 100 mg

or

3. Valsartan 320 mg + Atorvastatin 40 mg + Aspirin 100 mg

or

4. Valsartan 320 mg + Atorvastatin 80 mg + Aspirin100 mg

or

5. Valsartan 80 mg + Atorvastatin 40 mg + Aspirin 100 mg

or

6. Valsartan 80 mg + Atorvastatin 80 mg + Aspirin 100 mg

or

7. Valsartan 80 mg + Atorvastatin 20 mg + Aspirin 100 mg*

or

8. Valsartan 160 mg + Atorvastatin 20 mg + Aspirin 100 mg*

or

9. Valsartan 320 mg + Atorvastatin 20 mg + Aspirin 100 mg*

• The use of these formulations of the cardiovascular polypill will be restricted to cases of Statin-Related Muscle Symptoms (SRMS)

Colchicine-placebo 0.5 mg

Intervention Type: DRUG

Matching Colchicine-placebo 0.5 mg once daily

Group 3

Usual care + Colchicine 0.5 mg once daily

Group Type: EXPERIMENTAL

Colchicine 0.5 mg

Intervention Type: DRUG

Colchicine 0.5 mg once daily

Usual Care Group

Intervention Type: DRUG

Patients allocated to the usual care arm will receive standard of care therapies for secondary prevention according to the guidelines. Drugs and doses will be left at the discretion of the treating physicians.

Group 4

Usual care + Colchicine placebo 0.5 mg once daily

Group Type: EXPERIMENTAL

Usual Care Group

Intervention Type: DRUG

Patients allocated to the usual care arm will receive standard of care therapies for secondary prevention according to the guidelines. Drugs and doses will be left at the discretion of the treating physicians.

Colchicine-placebo 0.5 mg

Intervention Type: DRUG

Matching Colchicine-placebo 0.5 mg once daily

Interventions

Cardiovascular Polypill (Valsartan, Atorvastatin, Aspirin)

Cardiovascular Polypill contains Valsartan, Atorvastatin, Aspirin

1. Valsartan 160 mg + Atorvastatin 40 mg + Aspirin 100 mg

or

2. Valsartan 160 mg + Atorvastatin 80 mg + Aspirin 100 mg

or

3. Valsartan 320 mg + Atorvastatin 40 mg + Aspirin 100 mg

or

4. Valsartan 320 mg + Atorvastatin 80 mg + Aspirin100 mg

or

5. Valsartan 80 mg + Atorvastatin 40 mg + Aspirin 100 mg

or

6. Valsartan 80 mg + Atorvastatin 80 mg + Aspirin 100 mg

or

7. Valsartan 80 mg + Atorvastatin 20 mg + Aspirin 100 mg*

or

8. Valsartan 160 mg + Atorvastatin 20 mg + Aspirin 100 mg*

or

9. Valsartan 320 mg + Atorvastatin 20 mg + Aspirin 100 mg*

• The use of these formulations of the cardiovascular polypill will be restricted to cases of Statin-Related Muscle Symptoms (SRMS)

Intervention Type: DRUG

Colchicine 0.5 mg

Colchicine 0.5 mg once daily

Intervention Type: DRUG

Usual Care Group

Patients allocated to the usual care arm will receive standard of care therapies for secondary prevention according to the guidelines. Drugs and doses will be left at the discretion of the treating physicians.

Intervention Type: DRUG

Colchicine-placebo 0.5 mg

Matching Colchicine-placebo 0.5 mg once daily

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Individuals aged ≥ 45 years AND
• Signature of the Informed Consent Form (ICF) AND at least one of the following criteria:
• Previous atherothrombotic cardiovascular event (acute coronary syndrome, ischemic stroke, high-risk transient ischemic stroke, acute limb ischemia/arterial occlusion, or non-traumatic limb amputation) AND/OR
• Previous arterial revascularization (percutaneous, surgical, and/or hybrid) OR
• Diagnosis of significant atherosclerotic disease with ≥ 50% obstruction in any arterial territory (coronary, cerebrovascular, or peripheral), in the absence of a prior cardiovascular event or arterial revascularization.

Exclusion Criteria

• Pregnant or lactating women;
• Women of childbearing age who do not use any form of contraception;
• Known history of chronic kidney disease, stage ≥ 4 (estimated glomerular filtration rate ≤ 30 mL/min, if available);
• Known history of cirrhosis or severe liver disease (e.g., transaminase levels > 3 times the upper limit of normal, if available);
• Known history of inflammatory muscle disease (e.g., dermatomyositis or polymyositis) or creatine phosphokinase (CPK) levels > 3 times the upper limit of normal, if available);
• Known history of moderate or severe valvular heart disease with anticipated need for valvular intervention within the next 12 months;
• Planned arterial revascularization (inclusion is possible 30 days after completion of all planned procedures);
• Left ventricular ejection fraction ≤40% (with the exception of patients with documented intolerance to ACE inhibitors and/or sacubitril/valsartan, who remain eligible for study enrollment);
• Heart failure with functional class ≥ III according to the New York Heart Association (NYHA), regardless of left ventricular ejection fraction;
• Blood pressure < 120/80 mmHg in the absence of antihypertensive therapy;
• Life expectancy ≤ 12 months;
• Acute arterial event (acute coronary syndrome, non-cardioembolic ischemic stroke, acute limb ischemia) in the past 30 days;
• Substance abuse/alcoholism;
• Psychiatric and/or neurodegenerative disorder limiting self-care capacity;
• Concurrent participation in another randomized clinical trial;
• Contraindication to any component of the polypill;
• Current or planned use of oral anticoagulant therapy within the next 12 months (except rivaroxaban 2.5 mg twice daily for patients with peripheral artery disease);
• High risk of bleeding (e.g., but not limited to: blood dyscrasias, hemophilia, previous gastrointestinal or central nervous system bleeding);
• Contraindication to colchicine;
• Current use of colchicine.

• Minimum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hospital do Coracao

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Pedro Gabriel Melo de Barros e Silva, P.h.D

Role: STUDY_CHAIR

Hcor Research Institute

Lucas tramujas, M.D

Role: PRINCIPAL_INVESTIGATOR

Hcor Research Institute

Erlon Oliveira de Abreu-Silva, M.D

Role: PRINCIPAL_INVESTIGATOR

Hcor Research Institute

Locations

Centro de Pesquisas Clínicas Dr. Marco Mota

Maceió, Alabama, Brazil

Site Status: RECRUITING

Secretária da Saúde do Estado do Ceará - Hospital de Messejana Dr. Carlos Alberto Studart Gomes

Messejana, Ceará, Brazil

Site Status: RECRUITING

Empresa Brasileira de Serviços Hospitalares - EBSERCH - Hospital de Ensino Dr. Washington Antônio de Barros- HU-UNIVASF

Petrolina, Pernambuco, Brazil

Site Status: RECRUITING

Centro de Pesquisa Cardiolima

Teresina, Piauí, Brazil

Site Status: RECRUITING

Fundação Técnico Educacional Souza Marques

Rio de Janeiro, Rio de Janeiro, Brazil

Site Status: RECRUITING

Fundação Universitária de Cardiologia - ICFUC

Porto Alegre, Rio Grande do Sul, Brazil

Site Status: RECRUITING

Instituto de Pesquisa e Ensino em Saúde - IPES

Porto Velho, Rondônia, Brazil

Site Status: RECRUITING

CMEP - Centro Multidisciplinar de Ensino especializado e Pesquisa

Joinville, Santa Catarina, Brazil

Site Status: RECRUITING

Hospital Universitário São Francisco na Providência de Deus

Bragança Paulista, São Paulo, Brazil

Site Status: RECRUITING

Fundação Faculdade Regional de Medicina São José do Rio Preto

São José do Rio Preto, São Paulo, Brazil

Site Status: RECRUITING

CIPES - Centro Internacional de Pesquisa Clínica

São José dos Campos, São Paulo, Brazil

Site Status: RECRUITING

Hcor

São Paulo, São Paulo, Brazil

Site Status: RECRUITING

Centro de Pesquisa Cetrus

São Paulo, São Paulo, Brazil

Site Status: RECRUITING

Countries

Brazil

Facility Contacts

Marco Mota, Principal Investigator

Role: primary

centrodepesquisasclinicas@cesmac.edu.br

+55 82 3215-5032

João David de Souza Neto, Principal Investigator

Role: primary

unidadepesquisaclinica@gmail.com

+55 85 399810 6905

Polyana Evangelista Lima, Principal Investigator

Role: primary

ancianato@portalbethesda.org.br

+55 87 2101 6504

Carlos Eduardo Batista Lima

Role: primary

admin@cardiolima.com.br

+55 86 3085 3048

Fabio Akio Nishijuka, Principal Investigator

Role: primary

cepmsm@souzamarques.br

+55 21 2128-4900

Maico Furlanetto, Principal Investigator

Role: primary

pesquisaclinica@cardiologia.org.br

+55 51 3230 3860

Marcus Vinicius Nunes Batista

Role: primary

ipesrondonia@gmail.com

+55 69 9378 7257

Conrado Roberto Hoffmann Filho

Role: primary

pesquisa3@pesquisacmep.com.br

+55 47 9220 6886

Murillo de Oliveira Antunes

Role: primary

cepec.husf@alsf.org.br

+55 11 2490 1366

Marcelo Arruda Nakazone, Principal Investigator

Role: primary

coordenação.cardio@centrodepesquisacip.com.br

+55 17 3201-5054

Fabiana Marcondes, Principal Investigator

Role: primary

contato@cipes.com.br

+55 12 99726 2171

Lucas Tramujas, Principal Investigator

Role: primary

ltramujas@hcor.com.br

+55 11 96910-7556

Pablo de Oliveira Antunes

Role: primary

pesquisa@cetrus.com.br

+55 11 91513 0651

References

Tramujas L, Nogueira A, Felix N, Maia I, de Barros E Silva PGM, Cavalcanti AB, Abizaid A. Trends in colchicine use across the spectrum of coronary artery disease. Vascul Pharmacol. 2025 Jun;159:107502. doi: 10.1016/j.vph.2025.107502. Epub 2025 May 13. No abstract available.

Reference Type: BACKGROUND

PMID: 40373935 (View on PubMed)

de Barros E Silva PGM, do Nascimento CT, Pedrosa RP, Nakazone MA, do Nascimento MU, de Araujo Melo L, Junior OLS, Zimmermann SL, de Melo RMV, Bergo RR, Precoma DB, Tramujas L, Lima EG, Dantas JMM, do Amaral Baruzzi AC, Flumignan RLG, de Oliveira Paiva MSM, Gowdak LHW, de Carvalho PN, de Figueiredo Neto JA, Silvestre OM, Fioranelli A, Vieira RD', Horak ACP, Miyada DHK, Kojima FCS, de Oliveira JS, de Oliveira Silva L, Pavanello R, Ramacciotti E, Lopes RD; NEAT Investigators. Primary results of the brazilian registry of atherothrombotic disease (NEAT). Sci Rep. 2024 Feb 20;14(1):4222. doi: 10.1038/s41598-024-54516-9.

Reference Type: BACKGROUND

PMID: 38378735 (View on PubMed)

de Abreu-Silva EO, Siepmann M, Siepmann T. Polypills in the Management of Cardiovascular Risk-A Perspective. J Clin Med. 2024 Sep 16;13(18):5487. doi: 10.3390/jcm13185487.

Reference Type: BACKGROUND

PMID: 39336974 (View on PubMed)

Tramujas L, Nogueira A, Felix N, de Barros E Silva PGM, Abizaid A, Cavalcanti AB. Association of colchicine use with cardiovascular and limb events in peripheral artery disease: Insights from a retrospective cohort study. Atherosclerosis. 2024 Nov;398:118563. doi: 10.1016/j.atherosclerosis.2024.118563. Epub 2024 Aug 9.

Reference Type: BACKGROUND

PMID: 39299823 (View on PubMed)

Other Identifiers

EPOCA TRIAL

Identifier Type: -

Identifier Source: org_study_id