Clinical trial NCT06930885: Evaluation of a POlypill and Colchicine for Risk Reduction in Patients With Established Atherosclerotic Cardiovascular Disease
Official title: Evaluation of a POlypill and Colchicine for Risk Reduction in Patients With Established Atherosclerotic Cardiovascular Disease: The EPOCA Randomized Clinical Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Atherothrombotic Diseases
Atherosclerotic Cardiovascular Disease (ASCVD)
Keywords: Atherothrombotic diseases
Atherosclerotic cardiovascular disease
Polypill
Colchicine
Lead sponsor: Hospital do Coracao
Sponsor class: OTHER
First posted: 2025-04-16
Enrollment: 7713
Sex: ALL
Minimum age (years): 45
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Intervention model description: 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; Cardiovascular polypill usual care + Colchicine 0.5 mg once daily; or usual care + Colchicine placebo once daily.
Primary purpose: TREATMENT

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 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.

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, 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;
* Chronic kidney disease, stage ≥ 4 (eGFR ≤ 30 ml/min);
* History of cirrhosis or severe liver disease (transaminase levels exceeding three times the upper limit of normal) in the past 12 months;
* History of inflammatory muscle disease (e.g., dermatomyositis and polymyositis) or creatine phosphokinase (CPK) levels exceeding three times the upper limit of normal in the past 12 months;
* History of moderate to severe valvular heart disease with planned valve intervention within the next 12 months;
* Planned arterial revascularization (inclusion is possible 30 days after completion of all planned procedures);
* Heart failure with functional class ≥ III according to the New York Heart Association (NYHA);
* 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;
* Use of oral anticoagulants (at the time of randomization or under evaluation/planned use in the next 12 months);
* 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.

Primary outcomes:
measure: Primary efficacy endpoint: Major adverse cardiovascular and limb events (MACLE)
timeFrame: Through study completion, an estimated average of 3 years
Secondary outcomes:
measure: Key secondary endpoint: Major adverse cardiovascular events (MACE)
timeFrame: Through study completion, an estimated average of 3 years
measure: Cardiovascular death
timeFrame: Through study completion, an estimated average of 3 years
measure: Non-fatal type 1 myocardial infarction
timeFrame: Through study completion, an estimated average of 3 years
measure: Non-fatal ischemic stroke
timeFrame: Through study completion, an estimated average of 3 years
Other outcomes:
measure: Change in Treatment Adherence
timeFrame: Through study completion, an estimated average of 3 years
measure: Change in Systolic and Diastolic Blood Pressure (SBP and DBP)
timeFrame: Through study completion, an estimated average of 3 years
measure: Change in serum LDL-c concentrations
timeFrame: Through study completion, an estimated average of 3 years
measure: Change in serum concentrations of high-sensitivity C-reactive protein (hs-CRP)
timeFrame: Through study completion, an estimated average of 3 years
measure: Proportion of individuals with controlled blood pressure
timeFrame: Through study completion, an estimated average of 3 years
measure: Proportion of individuals with LDL-c levels at target
timeFrame: Through study completion, an estimated average of 3 years
measure: Change in Quality of Life
timeFrame: Through study completion, an estimated average of 3 years
measure: Safety endpoint: All-cause death
timeFrame: Through study completion, an estimated average of 3 years
measure: Safety endpoint: Bleeding
timeFrame: Through study completion, an estimated average of 3 years
measure: Safety endpoint: Hospitalization for sepsis
timeFrame: Through study completion, an estimated average of 3 years
measure: Safety endpoint: new diagnonis of cancer
timeFrame: Through study completion, an estimated average of 3 years
Locations:
Study officials:
affiliation: Hcor Research Institute
name: Pedro Gabriel Melo de Barros e Silva, P.h.D
role: STUDY_CHAIR
affiliation: Hcor Research Institute
name: Lucas tramujas, M.D
role: PRINCIPAL_INVESTIGATOR
affiliation: Hcor Research Institute
name: Erlon Oliveira de Abreu-Silva, M.D
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.