Colchicine in Belgium in Patients With Coronary Artery Disease After Percutaneous Coronary Intervention

This is a prospective, randomised, double-blind, multicenter, placebo-controlled phase III pragmatic superiority trial comparing colchicine 0.5 mg with placebo administered orally once-daily in up to 2770 participants with CAD treated with PCI. Participants will be randomised in a 1:1 ratio to receive either colchicine 0.5 mg or placebo as an adjunct to standard of care. The trial is event driven with trial closure being performed when the targeted number of 566 primary endpoint events has been reached.

Participants will be seen by the site staff 1 month after randomisation and thereafter every 12 months as per standard of care (SOC) and for IMP dispense and compliance, completing questionnaires and outcome event assessment until end of study. After the first month, a telephone visit will be scheduled every 6 months in between two standard of care on-site visits.

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):

• Age ≥ year
• Diabetes mellitus, on treatment or new diagnosis with HbA1c ≥6.5%
• Current smoking
• Treated hypertension or lood pressure systolic ≥ 4 mmHg or diastolic ≥ mmHg
• Total cholesterol >240 mg/dl untreated, or treated LDL >70 mg/dl
• HDL <40 mg/dl
• hsCRP >2 mg/L AND chronic coronary syndrome (CCS)
• eGFR <60 ml/min (MDRD)
• 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.

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 or other condition 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 cardiovascular intervention known on the day of screening.
• Currently enrolled in another investigational trial.
• Considered to be an unsuitable candidate by the investigator.