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Effect of Colchicine in Patients With Myocardial Infarction

Phase 2
Withdrawn
Conditions
Myocardium; Injury
Myocardial Infarction
Myocardial Ischemia
Interventions
Drug: Placebo oral tablet
Registration Number
NCT04218786
Lead Sponsor
Shifa Tameer-e-Millat University
Brief Summary

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

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.

Recruitment & Eligibility

Status
WITHDRAWN
Sex
All
Target Recruitment
Not specified
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Placebo groupPlacebo oral tabletThis group will receive a placebo drug with a similar shape and mass as that to experimental drug
Colchicine GroupColchicineThis group will receive low dose colchicine, 0.5 mg.
Primary Outcome Measures
NameTimeMethod
Major cardiovascular adverse events (number of events)3 months

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

Secondary Outcome Measures
NameTimeMethod
Creatine Kinase-Myocardial Band (IU/L)3 months

This workup will be recorded on the same questionnaire as a numerical value with its specific unit of measure upon followup of patient.

Troponin I (ng/ml)3 months

This workup will be recorded on the same questionnaire as a numerical value with its specific unit of measure upon followup of patient.

C-reactive protein (mg/L)3 months

This workup will be recorded on the same questionnaire as a numerical value with its specific unit of measure upon followup of patient.

Trial Locations

Locations (1)

Rawalpindi Institute of Cardiology

🇵🇰

Rawalpindi, Pakistan

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