Polypill and Colchicine for Risk Reduction in Atherosclerotic Cardiovascular Disease (EPOCA)

Evaluation of a POlypill and Colchicine for Risk Reduction in Patients With Established Atherosclerotic Cardiovascular Disease: The EPOCA Randomized Clinical Trial

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.

Study Overview

• Status: Recruiting
• Conditions: Atherothrombotic Diseases; Atherosclerotic Cardiovascular Disease (ASCVD)
• Intervention / Treatment: Drug: Colchicine 0.5 mg; Drug: Colchicine-placebo 0.5 mg; Drug: Usual Care Group; Drug: Cardiovascular Polypill (Valsartan, Atorvastatin, Aspirin)

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.

• Study Type: Interventional
• Enrollment (Estimated): 7713
• Phase: Phase 3

Contacts and Locations

Study Locations

• Brazil
  • Alabama
    • Maceió, Alabama, Brazil, 57051160
      • Recruiting
      • Centro de Pesquisas Clínicas Dr. Marco Mota
      • Contact: Marco Mota, Principal Investigator; Phone Number: +55 82 3215-5032; Email: centrodepesquisasclinicas@cesmac.edu.br
  • Ceará
    • Messejana, Ceará, Brazil
      • Recruiting
      • Secretária da Saúde do Estado do Ceará - Hospital de Messejana Dr. Carlos Alberto Studart Gomes
      • Contact: João David de Souza Neto, Principal Investigator; Phone Number: +55 85 399810 6905; Email: unidadepesquisaclinica@gmail.com
  • Pernambuco
    • Petrolina, Pernambuco, Brazil
      • Recruiting
      • Empresa Brasileira de Serviços Hospitalares - EBSERCH - Hospital de Ensino Dr. Washington Antônio de Barros- HU-UNIVASF
      • Contact: Polyana Evangelista Lima, Principal Investigator; Phone Number: +55 87 2101 6504; Email: ancianato@portalbethesda.org.br
  • Piauí
    • Teresina, Piauí, Brazil
      • Recruiting
      • Centro de Pesquisa Cardiolima
      • Contact: Carlos Eduardo Batista Lima; Phone Number: +55 86 3085 3048; Email: admin@cardiolima.com.br
  • Rio Grande do Sul
    • Porto Alegre, Rio Grande do Sul, Brazil
      • Recruiting
      • Fundação Universitária de Cardiologia - ICFUC
      • Contact: Maico Furlanetto, Principal Investigator; Phone Number: +55 51 3230 3860; Email: pesquisaclinica@cardiologia.org.br
  • Rio de Janeiro
    • Rio de Janeiro, Rio de Janeiro, Brazil, 22.793-140
      • Recruiting
      • Fundação Técnico Educacional Souza Marques
      • Contact: Fabio Akio Nishijuka, Principal Investigator; Phone Number: +55 21 2128-4900; Email: cepmsm@souzamarques.br
  • Rondônia
    • Porto Velho, Rondônia, Brazil
      • Recruiting
      • Instituto de Pesquisa e Ensino em Saúde - IPES
      • Contact: Marcus Vinicius Nunes Batista; Phone Number: +55 69 9378 7257; Email: ipesrondonia@gmail.com
  • Santa Catarina
    • Joinville, Santa Catarina, Brazil
      • Recruiting
      • CMEP - Centro Multidisciplinar de Ensino especializado e Pesquisa
      • Contact: Conrado Roberto Hoffmann Filho; Phone Number: +55 47 9220 6886; Email: pesquisa3@pesquisacmep.com.br
  • São Paulo
    • Bragança Paulista, São Paulo, Brazil
      • Recruiting
      • Hospital Universitário São Francisco na Providência de Deus
      • Contact: Murillo de Oliveira Antunes; Phone Number: +55 11 2490 1366; Email: cepec.husf@alsf.org.br
    • São José do Rio Preto, São Paulo, Brazil, 15.090-000
      • Recruiting
      • Fundação Faculdade Regional de Medicina São José do Rio Preto
      • Contact: Marcelo Arruda Nakazone, Principal Investigator; Phone Number: +55 17 3201-5054; Email: coordenação.cardio@centrodepesquisacip.com.br
    • São José dos Campos, São Paulo, Brazil
      • Recruiting
      • CIPES - Centro Internacional de Pesquisa Clínica
      • Contact: Fabiana Marcondes, Principal Investigator; Phone Number: +55 12 99726 2171; Email: contato@cipes.com.br
    • São Paulo, São Paulo, Brazil, 04004-030
      • Recruiting
      • Hcor
      • Contact: Lucas Tramujas, Principal Investigator; Phone Number: +55 11 96910-7556; Email: ltramujas@hcor.com.br
    • São Paulo, São Paulo, Brazil
      • Recruiting
      • Centro de Pesquisa Cetrus
      • Contact: Pablo de Oliveira Antunes; Phone Number: +55 11 91513 0651; Email: pesquisa@cetrus.com.br

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1; Cardiovascular Polypill + Colchicine 0.5 mg once daily	Drug: Colchicine 0.5 mg; Colchicine 0.5 mg once daily; Drug: Cardiovascular Polypill (Valsartan, Atorvastatin, Aspirin); Cardiovascular Polypill contains Valsartan, Atorvastatin, Aspirin; Valsartan 160 mg + Atorvastatin 40 mg + Aspirin 100 mgor; Valsartan 160 mg + Atorvastatin 80 mg + Aspirin 100 mgor; Valsartan 320 mg + Atorvastatin 40 mg + Aspirin 100 mgor; Valsartan 320 mg + Atorvastatin 80 mg + Aspirin100 mgor; Valsartan 80 mg + Atorvastatin 40 mg + Aspirin 100 mgor; Valsartan 80 mg + Atorvastatin 80 mg + Aspirin 100 mgor; Valsartan 80 mg + Atorvastatin 20 mg + Aspirin 100 mg*or; Valsartan 160 mg + Atorvastatin 20 mg + Aspirin 100 mg*or; 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)
Experimental: Group 2; Cardiovascular Polypill + Colchicine placebo 0.5 mg once daily	Drug: Colchicine-placebo 0.5 mg; Matching Colchicine-placebo 0.5 mg once daily; Drug: Cardiovascular Polypill (Valsartan, Atorvastatin, Aspirin); Cardiovascular Polypill contains Valsartan, Atorvastatin, Aspirin; Valsartan 160 mg + Atorvastatin 40 mg + Aspirin 100 mgor; Valsartan 160 mg + Atorvastatin 80 mg + Aspirin 100 mgor; Valsartan 320 mg + Atorvastatin 40 mg + Aspirin 100 mgor; Valsartan 320 mg + Atorvastatin 80 mg + Aspirin100 mgor; Valsartan 80 mg + Atorvastatin 40 mg + Aspirin 100 mgor; Valsartan 80 mg + Atorvastatin 80 mg + Aspirin 100 mgor; Valsartan 80 mg + Atorvastatin 20 mg + Aspirin 100 mg*or; Valsartan 160 mg + Atorvastatin 20 mg + Aspirin 100 mg*or; 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)
Experimental: Group 3; Usual care + Colchicine 0.5 mg once daily	Drug: Colchicine 0.5 mg; Colchicine 0.5 mg once daily; 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.
Experimental: Group 4; Usual care + Colchicine placebo 0.5 mg once daily	Drug: Colchicine-placebo 0.5 mg; Matching Colchicine-placebo 0.5 mg once daily; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary efficacy endpoint: Major adverse cardiovascular and limb events (MACLE)	Time to cardiovascular death, non-fatal type 1 myocardial infarction, non-fatal ischemic stroke, urgent arterial revascularization, and non-traumatic major lower limb amputation	Through study completion, an estimated average of 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Key secondary endpoint: Major adverse cardiovascular events (MACE)	Time to cardiovascular mortality, non-fatal type 1 myocardial infarction, and non-fatal ischemic stroke.	Through study completion, an estimated average of 3 years
Cardiovascular death	Time to cardiovascular death	Through study completion, an estimated average of 3 years
Non-fatal type 1 myocardial infarction	Time to non-fatal type 1 myocardial infarction	Through study completion, an estimated average of 3 years
Non-fatal ischemic stroke	Time to non-fatal ischemic stroke	Through study completion, an estimated average of 3 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Systolic and Diastolic Blood Pressure (SBP and DBP)	Systolic and diastolic blood pressure will be assessed and summarized at each timepoint.	Through study completion, an estimated average of 3 years
Change in serum LDL-c concentrations	Non-fasting blood analysis will be collected and LDL cholesterol level evaluated at each timepoint.	Through study completion, an estimated average of 3 years
Change in serum concentrations of high-sensitivity C-reactive protein (hs-CRP)	High-sensitivity C-reactive protein (hs-CRP) will be colllected and evaluated at each timepoint	Through study completion, an estimated average of 3 years
Proportion of individuals with controlled blood pressure	Systolic and diastolic blood pressure will be collected and the proportions of patients with controled blood pressure will be summarized at each timepoint	Through study completion, an estimated average of 3 years
Proportion of individuals with LDL-c levels at target	Non-fasting blood analysis will be collected and the proportion of individuals with LDL-c levels at target will be evaluated at each timepoint	Through study completion, an estimated average of 3 years
Safety endpoint: All-cause death	Time to all-cause death	Through study completion, an estimated average of 3 years
Safety endpoint: Bleeding	It will be assessed according to the definitions of the Bleeding Academic Research Consortium.	Through study completion, an estimated average of 3 years
Safety endpoint: Hospitalization for sepsis	Time to hospitalization for sepsis	Through study completion, an estimated average of 3 years
Safety endpoint: new diagnonis of cancer	Time of ocurrence of new diagnosis of cancer	Through study completion, an estimated average of 3 years
Change in Treatment Adherence	It will be assessed through the 9-item adapted Hill-Bone Medication Adherence Scale. The adapted 9-item Hill-Bone Medication Adherence Scale consists of 9 questions, each rated on a 4-point Likert scale ('all of the time', 'most of the time', 'some of the time', 'none of the time'). Item scores range from 1 to 4, yielding a total score between 9 and 36. Higher scores reflect poorer adherence, whereas lower scores reflect better adherence.	Through study completion, an estimated average of 3 years
Change in Quality of Life	The European Quality of Life - 5 Dimensions 5 Levels (EQ-5D-5L) Questionnaire will be administered at each timepoint to evaluate changes in quality of life. The EQ-5D-5L includes a descriptive system and a visual analogue scale (EQ VAS). The descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression-each with five levels of severity. Responses generate a five-digit health profile. The EQ VAS captures the participant's self-rated health on a visual scale from 0 ("the worst health you can imagine") to 100 ("the best health you can imagine").	Through study completion, an estimated average of 3 years

Collaborators and Investigators

• Sponsor: Hospital do Coracao
• Investigators: Study Chair: Pedro Gabriel Melo de Barros e Silva, P.h.D, Hcor Research Institute; Principal Investigator: Lucas tramujas, M.D, Hcor Research Institute; Principal Investigator: Erlon Oliveira de Abreu-Silva, M.D, Hcor Research Institute

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): June 12, 2025
• Primary Completion (Estimated): May 1, 2031
• Study Completion (Estimated): May 1, 2031

Study Registration Dates

• First Submitted: April 9, 2025
• First Submitted That Met QC Criteria: April 15, 2025
• First Posted (Actual): April 16, 2025

Study Record Updates

• Last Update Posted (Actual): January 22, 2026
• Last Update Submitted That Met QC Criteria: January 21, 2026
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: Colchicine; Atherosclerotic cardiovascular disease; Polypill; Atherothrombotic diseases
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Atherosclerosis; Amino Acids, Peptides, and Proteins; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fatty Acids; Lipids; Azoles; Hydrocarbons; Hydrocarbons, Cyclic; Alkaloids; Hydrocarbons, Aromatic; Amino Acids; Phenols; Benzene Derivatives; Pyrroles; Heptanoic Acids; Amino Acids, Essential; Salicylates; Hydroxybenzoates; Tetrazoles; Valine; Amino Acids, Branched-Chain; Atorvastatin; Valsartan; Aspirin; Colchicine
• Other Study ID Numbers: EPOCA TRIAL

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Our data dissemination plan will follow the rules of the Hcor research institute
• IPD Sharing Time Frame: 1 year after the publication
• IPD Sharing Access Criteria: Submission of a statistical analysis plan for the purposed analyses. Compliance with Brazilian. data privacy law.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No