Polypill and Colchicine for Risk Reduction in Atherosclerotic Cardiovascular Disease

NCT06930885 | Recruiting Phase 3 DMC

• 1 other identifier: EPOCA TRIAL
• Study Type: interventional
• Target: 7,713
• Locations: 1 country
• Sites: 13

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.

Conditions

Atherothrombotic Diseases; Atherosclerotic Cardiovascular Disease (ASCVD)

Keywords

Atherothrombotic diseases; Atherosclerotic cardiovascular disease; Polypill; Colchicine

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Key secondary endpoint: Major adverse cardiovascular events (MACE)

  Through study completion, an estimated average of 3 years

• Cardiovascular death

  Through study completion, an estimated average of 3 years

• Non-fatal type 1 myocardial infarction

  Through study completion, an estimated average of 3 years

• Non-fatal ischemic stroke

  Through study completion, an estimated average of 3 years

Other Outcomes (11)

• Change in Treatment Adherence

  Through study completion, an estimated average of 3 years

• Change in Systolic and Diastolic Blood Pressure (SBP and DBP)

  Through study completion, an estimated average of 3 years

• Change in serum LDL-c concentrations

  Through study completion, an estimated average of 3 years

Study Arms (4)

Group 1

EXPERIMENTAL

Cardiovascular Polypill + Colchicine 0.5 mg once daily

Drug: Cardiovascular Polypill (Valsartan, Atorvastatin, Aspirin); Drug: Colchicine 0.5 mg

Group 2

EXPERIMENTAL

Cardiovascular Polypill + Colchicine placebo 0.5 mg once daily

Drug: Cardiovascular Polypill (Valsartan, Atorvastatin, Aspirin); Drug: Colchicine-placebo 0.5 mg

Group 3

EXPERIMENTAL

Usual care + Colchicine 0.5 mg once daily

Drug: Colchicine 0.5 mg; Drug: Usual Care Group

Group 4

EXPERIMENTAL

Usual care + Colchicine placebo 0.5 mg once daily

Drug: Usual Care Group; Drug: Colchicine-placebo 0.5 mg

Interventions

Cardiovascular Polypill (Valsartan, Atorvastatin, Aspirin) 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)

Group 1; Group 2

Colchicine 0.5 mg DRUG

Colchicine 0.5 mg once daily

Group 1; Group 3

Usual Care Group 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 3; Group 4

Colchicine-placebo 0.5 mg DRUG

Matching Colchicine-placebo 0.5 mg once daily

Group 2; Group 4

Eligibility Criteria

• Age: 45 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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;
• 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;

Sponsors & Collaborators

• Hospital do Coracao: lead

Study Sites (13)

Centro de Pesquisas Clínicas Dr. Marco Mota

Maceió, Alabama, 57051160, Brazil

RECRUITING

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

Messejana, Ceará, Brazil

RECRUITING

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

Petrolina, Pernambuco, Brazil

RECRUITING

Centro de Pesquisa Cardiolima

Teresina, Piauí, Brazil

RECRUITING

Fundação Técnico Educacional Souza Marques

Rio de Janeiro, Rio de Janeiro, 22.793-140, Brazil

RECRUITING

Fundação Universitária de Cardiologia - ICFUC

Porto Alegre, Rio Grande do Sul, Brazil

RECRUITING

Instituto de Pesquisa e Ensino em Saúde - IPES

Porto Velho, Rondônia, Brazil

RECRUITING

CMEP - Centro Multidisciplinar de Ensino especializado e Pesquisa

Joinville, Santa Catarina, Brazil

RECRUITING

Hospital Universitário São Francisco na Providência de Deus

Bragança Paulista, São Paulo, Brazil

RECRUITING

Fundação Faculdade Regional de Medicina São José do Rio Preto

São José do Rio Preto, São Paulo, 15.090-000, Brazil

RECRUITING

CIPES - Centro Internacional de Pesquisa Clínica

São José dos Campos, São Paulo, Brazil

RECRUITING

Hcor

São Paulo, São Paulo, 04004-030, Brazil

RECRUITING

Centro de Pesquisa Cetrus

São Paulo, São Paulo, Brazil

RECRUITING

Related Publications (4)

• 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.

  PMID: 40373935 BACKGROUND

• 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.

  PMID: 38378735 BACKGROUND

• 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.

  PMID: 39336974 BACKGROUND

• 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.

  PMID: 39299823 BACKGROUND

MeSH Terms

Conditions

Atherosclerosis

Interventions

Valsartan; Atorvastatin; Aspirin; Colchicine

Condition Hierarchy (Ancestors)

Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases

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; Pyrroles; Heptanoic Acids; Fatty Acids; Lipids; Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Alkaloids

Study Officials

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

  Hcor Research Institute

  STUDY CHAIR

• Lucas tramujas, M.D

  Hcor Research Institute

  PRINCIPAL INVESTIGATOR

• Erlon Oliveira de Abreu-Silva, M.D

  Hcor Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The polypill factor will be open-label and controlled by standard treatment (usual care). The colchicine factor will be blinded and controlled by placebo.
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: They will be randomized, simultaneously, in a 1:1:1:1 ratio to polypill or usual care, and colchicine 0.5 mg once daily versus placebo, in a 2x2 factorial design. Therefore, the study will have four possible groups: Cardiovascular polypill + colchicine 0.5 mg once daily; Cardiovascular polypill + Colchicine placebo once daily; Usual care + Colchicine 0.5 mg once daily; or Usual care + Colchicine placebo once daily.

Study Record Dates

• First Submitted: April 9, 2025
• First Posted: April 16, 2025
• Study Start: June 12, 2025
• Primary Completion (Estimated): May 1, 2031
• Study Completion (Estimated): May 1, 2031
• Last Updated: January 22, 2026

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: 1 year after the publication
• Access Criteria: Submission of a statistical analysis plan for the purposed analyses. Compliance with Brazilian. data privacy law.

Locations

BR (13)