Is Colchicine (0.5 mg/day) in addition to optimal medical therapy (OMT) effective in reducing cardiovascular outcomes in patients with acute ACS and evidence of persistent coronary inflammation?

Study sites: • National Hospital of Sri Lanka, Colombo 10 • CLINMARC, National Hospital of Sri Lanka, Colombo 10 • Kandy National Hospital • Colombo North Teaching Hospital, Ragama • Negombo District General Hospital, Negombo • Colombo South Teaching Hospital, Kalubowila • Teaching Hospital Polonnaruwa • General Sir John Kotelawala Defence University Hospital, Boralesgamuwa
* Jaffna Teaching Hospital *. Kurunegala Teaching Hospital

Randomisation:

A computer-generated sequence will be used to randomise the participants. Randomisation will stratify by statin dose (high dose vs none, low to moderate dose)

Study treatment

Eligible participants will be randomly allocated (randomization ratio of 1:1) to one of the following two treatment groups until the end of the study, that is when 600 primary endpoint events have occurred.

Study arms:

1. Experimental treatment arm: Colchicine 0.5mg, once daily + optimal medical therapy (OMT)

2. Standard treatment arm: Matching placebo + OMT

Run-in period

All the eligible and consented participants will undergo a single-blinded active run-in period with colchicine (0.5mg tablet daily for 28 days, study drug will be unknown to the participant).

Placebo A matched placebo tablet containing no active ingredient will be used as a comparator. This tablet will appear identical to the Colchicine tablet and the same storage and expiry conditions will apply. Placebo will contain: Lactose Monohydrate (super-tab), Magnesium Stearate BP (veg), Maize Starch (neutral), Povidone (K29-32)

1. Patients aged equal or greater than 18 years
2. Presentation with an Acute Coronary Syndrome (defined as acute myocardial infarction, with or without electrocardiographic evidence of ST-segment elevation, or high-risk unstable angina)
3. hs-CRP equal or greater than 1.0mg/L (at time of registration 4 - 52 weeks after discharge for an ACS event)
4. Willing and able to comply with all study requirements, including treatment, timing and/or nature of required assessments
5. Signed written informed consent

1. Any known intolerance to Colchicine
2. Pre-existing Colchicine treatment for greater than 7 days within the last 3 months
3. Current active myopathy with CK >3 x upper limit of normal
4. Severe liver disease or aminotransferase level > 3x upper limit of normal, within the last 3 months
5. Persistent blood dyscrasia (white cell count or platelet count < lower limit of normal), within the last 3 months
6. Estimated glomerular filtration rate (eGFR) <30 mL/min per 1.73m2 at time of registration
7. Prior or current therapy with a strong CYP3A4 inhibitor or inducer or calcineurin inhibitor
8. Active autoimmune disease or chronic inflammatory bowel disease (defined as any disease requiring long-term or frequent immunosuppression), where use of infliximab, cyclosporin, or azathioprine is current or likely.
9. Haematological malignancy which remains uncured or antineoplastic therapy within the last 3 months
10. Concurrent illness, including severe infection that may jeopardise the ability of the patient to undergo the procedures outlined in this protocol with reasonable safety
11. Any known comorbidities or conditions (e.g. psychiatric) or concomitant medications which may interact with the investigational product(s) or may compromise assessment of key outcomes.
12. Life expectancy of less than 3 years
13. Serious medical or psychiatric conditions that might limit the ability of the patient to comply with the protocol.
14. Pregnancy, lactation, or inadequate contraception. Women must be post-menopausal, infertile, or use a reliable means of contraception. Women of childbearing potential must have a negative pregnancy test done within 7 days prior to registration. Sexually active men must ensure that their partners use adequate contraception at all times when the trial medication is being consumed.