Evaluation of Colchicine Efficacy in Reducing Cardiovascular Events in Post-PCI Patients with Coronary Artery Disease: A Randomized, Placebo-Controlled Trial

Trial ID: 2023-505028-74-00
Protocol: COL BE PCI
Sponsor: Universitair Ziekenhuis Gent

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Diseases & Conditions

Coronary artery disease

Objectives

The primary objective of this study is to demonstrate that **colchicine** 0.5 mg daily reduces the first occurrence of a composite endpoint consisting of all-cause death, spontaneous (non-procedural) non-fatal myocardial infarction, non-fatal stroke, or coronary revascularisation in patients with **coronary artery disease** (CAD) treated with percutaneous coronary intervention (PCI). This is clinically relevant as it aims to establish the efficacy of colchicine in reducing major adverse cardiovascular events in this patient population.

Secondary objectives include providing additional support for the effectiveness of colchicine by comparing its effect versus placebo, when added to optimized medical therapy in patients with CAD treated with PCI, with regards to:

A specific cardiovascular composite endpoint consisting of cardiovascular death, spontaneous (non-procedural) non-fatal myocardial infarction, non-fatal stroke, or coronary revascularisation.
A specific composite of hard endpoints consisting of all-cause death, spontaneous (non-procedural) non-fatal myocardial infarction, non-fatal stroke.
Breakdown components of the primary outcome and atherosclerosis-related diseases.
Patient-reported outcomes based on the International Consortium for Health Outcome Measurement (ICHOM) Standard Set for CAD.

These secondary objectives aim to further elucidate the potential benefits of colchicine in various clinical scenarios related to CAD.

Participants

The clinical trial involves participants diagnosed with **coronary artery disease** (CAD) who have undergone percutaneous coronary intervention (PCI) and are receiving optimal medical therapy. The study population includes both male and female subjects aged 45 years and older. Participants are selected based on the presence of at least one additional risk factor, such as diabetes mellitus, current smoking, treated hypertension, elevated cholesterol levels, low HDL, high hsCRP, reduced eGFR, or a history of vascular disease. The trial also considers individuals with chronic coronary syndrome. Participants must be enrolled and randomized between 2 hours and 5 days post-PCI. The sponsor has not provided the total number of participants involved in the study. The trial includes a vulnerable population, and all participants have provided written informed consent. Lifestyle factors such as diet and physical activity are not specified in the available data.

Plans and Procedures

The clinical trial is designed to evaluate the efficacy of **colchicine** 0.5 mg daily in reducing the first occurrence of a composite endpoint in patients with **coronary artery disease** (CAD) who have undergone percutaneous coronary intervention (PCI). This is a randomized, double-blind, placebo-controlled trial, with participants receiving either colchicine or a placebo. The trial is expected to run from December 2023 to August 2027, with a maximum treatment period of 44 weeks for each participant.

Participants will be enrolled if they meet specific inclusion criteria, such as being 45 years or older, having CAD treated with PCI, and possessing at least one additional risk factor. The primary endpoint is the time from randomization to the first occurrence of a composite endpoint, including all-cause death, non-fatal myocardial infarction, non-fatal stroke, or coronary revascularization. Secondary endpoints include time to specific cardiovascular events and changes in participant-reported outcomes.

The sequence of study visits begins with a screening visit to confirm eligibility, followed by randomization between 2 hours and 5 days post-PCI. Follow-up visits will be scheduled to monitor the participants' health status and collect data on the primary and secondary endpoints. The end-of-study visit will conclude the trial for each participant, assessing the final outcomes and any adverse events.

Participant involvement is expected to last up to 44 weeks, with conditions for early termination including withdrawal of consent, significant protocol deviations, or adverse events that compromise participant safety. The trial aims to provide robust data on the potential benefits of colchicine in reducing cardiovascular events in this patient population.

Treatment

The clinical trial involves the administration of **Colchicine Tiofarma 500 microgram Tablets** as the experimental medication. This pharmaceutical product is formulated as a **tablet** and is intended for **oral** administration. The active substance in this medication is **colchicine**, a chemical compound. The dosage regimen for the trial specifies a maximum daily dose of 0.5 mg, with a total maximum dose of 671 mg over a treatment period of up to 44 days. The medication is manufactured by TIOFARMA BV and is identified by the marketing authorization number PL 17299/0003. The trial aims to evaluate the efficacy of colchicine in reducing the first occurrence of a composite endpoint in patients with coronary artery disease following percutaneous coronary intervention.

In addition to the experimental medication, the study includes the use of a **placebo** comparator, identified as **Placebo Colchicine 0.5 mg tablets**. The placebo is designed to mimic the appearance of the colchicine tablets but does not contain any active pharmaceutical ingredient. The placebo serves as a control to assess the true efficacy of the colchicine treatment by providing a baseline for comparison. The administration of the placebo follows the same oral route and dosing schedule as the active treatment, ensuring that any observed effects can be attributed to the active substance rather than the act of taking a tablet itself.

Efficacy

Efficacy in the clinical trial titled "COLchicine in BElgium in patients with coronary artery disease after Percutaneous Coronary Intervention" will be assessed through a series of predefined endpoints. The primary endpoint is the time from randomization to the first occurrence of a composite endpoint, which includes all-cause death, spontaneous (non-procedural) non-fatal **myocardial infarction** (Type 1, 4B & C), non-fatal stroke, or coronary revascularization. Secondary endpoints will further evaluate the time from randomization to the first occurrence of specific cardiovascular events, as well as changes in patient-reported outcomes over time.

Secondary endpoints include the time to first occurrence of a composite of specific cardiovascular endpoints, a composite of hard endpoints, and the breakdown components of the primary endpoint and atherosclerosis-related diseases. Additionally, the trial will assess changes from randomization to year 1 and to the end of the study in participant-reported outcomes using the ICHOM Standard Set for CAD, which includes the Seattle Angina Questionnaire (SAQ) Angina Frequency Scale, the Rose Dyspnea Scale, and the Patient Health Questionnaire PHQ-2 for depression.

The efficacy parameters will be collected and analyzed at various time points throughout the study, with specific attention to the occurrence of primary and secondary endpoints. The trial aims to demonstrate that colchicine 0.5 mg daily can reduce the first occurrence of these composite endpoints in patients with coronary artery disease treated with percutaneous coronary intervention.

Inclusion and Exclusion Criteria

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Inclusion Criteria

Age ≥45 years.
Coronary artery disease treated with PCI and optimal medical therapy, with at least one additional risk factor (based on SMART): a. Age ≥ year b. Diabetes mellitus, on treatment or new diagnosis with HbA1c ≥6.5% c. Current smoking d. Treated hypertension or lood pressure systolic ≥ 4 mmHg or diastolic ≥ mmHg e. Total cholesterol >240 mg/dl untreated, or treated LDL >70 mg/dl f. HDL <40 mg/dl g. hsCRP >2 mg/dl AND chronic coronary syndrome (CCS) h. eGFR <60 ml/min (MDRD) i. history of vascular disease: • CAD (PCI prior to index, CABG, MI) • stroke (ischemic or hemorrhagic) • carotid artery revascularisation • PAD (revascularisation, ABI <0.85 at rest, amputation due to atherosclerotic disease) • AAA (repair, distal aortic anteroposterior diameter >3.0cm)
Able to be enrolled/randomized between 2 hour and 5 days post PCI.
Written informed consent.

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Exclusion Criteria

Women who are pregnant, breastfeeding, or of childbearing potential who are not using an effective method of contraception. Or women who intend to donate oocytes.
Men who plan to father children during the study period or who are unwilling to use effective forms of contraception. Or men who intend to donate sperm.
Any contraindication or known intolerance to colchicine.
Chronic use of -or need for- colchicine.
Auto-immune disease requiring current or planned chronic systemic steroids, immunosuppressant or biologic drug targeting the immune system (for example, TNF blockers, anakinra, rituximab, abatacept, tocilizumab etc.).
Creatinine clearance <30 mL/min/1.73 m2.
Cirrhosis Child-Pugh stadium B and C, or acute severe liver disease
Neuromuscular disease or non-transient CK levels > 5 x ULN (unless due to MI).
History of cancer or lymphoproliferative disease within the last 3 years, other than successfully treated non-metastatic cutaneous squamous cell or basal cell carcinoma, or localized cervix carcinoma in situ.
Current or planned use of any strong inhibitor of CYP3A4 or p-glycoprotein: macrolide antibiotics (clarithromycin, telithromycin), azole antifungal agents (ketoconazole, voriconazole, fluconazole, itraconazole), cyclosporine, HIV medication (ritonavir, lopinavir, tipranavir, atazanavir, darunavir, indinavir, saquinavir).
Chronic diarrhea, or inflammatory owel disease (Crohn’s disease or ulcerative colitis).
Drug or alcohol abuse.
Planned coronary, carotid or peripheral revascularisation known on the day of screening.
Currently enrolled in another investigational trial.
Considered to be an unsuitable candidate by the investigator.