Effect of Colchicine in Patients With Myocardial Infarction

Study Overview
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Brief Summary
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Over the past years, a substantial volume of evidence has accumulated identifying inflammatory processes as key mediators of the deleterious effects of ischemia/reperfusion-related phenomena in patients presenting with ST-segment-elevation myocardial infarction (STEMI). Nevertheless, equally impressive is the lack of clinically applicable therapeutic strategies that could mitigate these processes, thus providing significant cardioprotection. Despite the well-known fact that inflammation plays an important role in coronary artery disease development and progression, there have been few attempts to systematically examine the potential role of anti-inflammatory treatment in this setting, possibly because of a lack in anti-inflammatory agents without the adverse cardiovascular safety profile of corticosteroids and nonsteroidal anti-inflammatory drugs. Colchicine is a substance with potent anti-inflammatory properties, having a unique mechanism of action, which allows for safe use in patients with cardiovascular disease. The purpose of the present clinical study is to test the hypothesis that a short course of treatment with colchicine could lead to reduced major adverse cardiovascular events (MACE) in acute MI.

Detailed Description
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Over the past years, a substantial volume of evidence has accumulated identifying inflammatory processes as key mediators of the deleterious effects of ischemia/reperfusion-related phenomena in patients presenting with ST-segment-elevation myocardial infarction (STEMI). Nevertheless, equally impressive is the lack of clinically applicable therapeutic strategies that could mitigate these processes, thus providing significant cardioprotection. Despite the well-known fact that inflammation plays an important role in coronary artery disease development and progression, there have been few attempts to systematically examine the potential role of anti-inflammatory treatment in this setting, possibly because of a lack in anti-inflammatory agents without the adverse cardiovascular safety profile of corticosteroids and nonsteroidal anti-inflammatory drugs. Some anti-inflammatory agents, like pexelizumab, are focused on complement cascade.Another agent is Varespladib, which targets sPLA2 that causes oxidative stress and inflammation. There are other therapeutic targets that have been widely investigated. Colchicine is a substance with potent anti-inflammatory properties, having a unique mechanism of action, which allows for safe use in patients with cardiovascular disease. Colchicine binds to non-polymerized tubulin, forming a stable complex that effectively inhibits the dynamic of microtubules, depolymerizing them. Thus, any process requiring changes in the cell cytoskeleton, such as cellular mitosis, exocytosis and neutrophil motility, is affected. Colchicine has an important effect on atrial myocytes, changing the atrial response to autonomic effects (reducing the sympathetic activity and increasing the parasympathetic one). Due to this particular mode of action, colchicine has been indicated in atrial fibrillation post-cardiac surgery. A similar trial is being conducted to investigate any effusions or syndromes that occur after myocardial infarction. The purpose of the present clinical study is to test the hypothesis that a short course of treatment with colchicine could lead to reduced major adverse cardiovascular events (MACE) in acute MI.

Official Title
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Outcomes of Low-dose Colchicine in Patients With Myocardial Infarction: A Randomized Controlled Trial

Conditions
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Myocardium; Injury, Myocardial Infarction, Myocardial Ischemia

Intervention / Treatment
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* Drug: Colchicine
* Drug: Placebo oral tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All patients 18 years or above presenting in emergency department with acute myocardial infarction. These patients will be requested to take the medication at the time of discharge after stabilization and management Exclusion Criteria: Patients with prior myocardial infarction 30 days before Patients with ischemic cardiomyopathy Age <18 or > 80 years Active inflammatory or infectious disease or known malignancy Known hypersensitivity to colchicine, renal failure (eGFR <30ml.min.1.73m) hepatic failure Stent thrombosis Cardiac arrest or cardiogenic shock as presenting symptoms

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Colchicine Group<br>This group will receive low dose colchicine, 0.5 mg. | Drug: Colchicine<br>* The tablet will be given once daily for the span of the study<br>|
| Placebo Comparator: Placebo group<br>This group will receive a placebo drug with a similar shape and mass as that to experimental drug | Drug: Placebo oral tablet<br>* The tablet will be given once daily for the span of the study<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major cardiovascular adverse events (number of events) | This outcome will be assessed using a questionnaire. The following headings will be used: Cardiovascular death (number of events) Non-fatal myocardial infarction (number of events) Resuscitated cardiac arrest (number of events) Hospitalization for unstable angina (number of events) For each heading, the total number of events will be recorded and the numbers will all be added to calculate 'Major Adverse Cardiovascular Events' in form of number of events. This outcome has no specific values of measure but a discrete numerical value | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Troponin I (ng/ml) | This workup will be recorded on the same questionnaire as a numerical value with its specific unit of measure upon followup of patient. | 3 months | 
| Creatine Kinase-Myocardial Band (IU/L) | This workup will be recorded on the same questionnaire as a numerical value with its specific unit of measure upon followup of patient. | 3 months | 
| C-reactive protein (mg/L) | This workup will be recorded on the same questionnaire as a numerical value with its specific unit of measure upon followup of patient. | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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colchicine; outcome: myocardial infarction