Effect of Colchicine in Patients With Myocardial Infarction

Sponsor

Shifa Tameer-e-Millat University (Other)

Overall Status

Suspended

CT.gov ID

NCT04218786

Collaborator

Rawalpindi Institute of Cardiology (Other)

800

Enrollment

Location

Arms

Anticipated Duration (Months)

133.8

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Myocardium; Injury Myocardial Infarction Myocardial Ischemia	Drug: Colchicine Drug: Placebo oral tablet	Phase 2

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

800 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Outcomes Assessor)

Primary Purpose:

Prevention

Official Title:

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

Anticipated Study Start Date :

Dec 1, 2025

Anticipated Primary Completion Date :

Mar 1, 2026

Anticipated Study Completion Date :

Jun 1, 2026

Arms and Interventions

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

Arm

Intervention/Treatment

Active Comparator: Colchicine Group

This group will receive low dose colchicine, 0.5 mg.

Drug: Colchicine

The tablet will be given once daily for the span of the study

Placebo Comparator: Placebo group

This group will receive a placebo drug with a similar shape and mass as that to experimental drug

Drug: Placebo oral tablet

The tablet will be given once daily for the span of the study

Outcome Measures

Primary Outcome Measures

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

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.
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.
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Rawalpindi Institute of Cardiology	Rawalpindi		Pakistan	46000

Sponsors and Collaborators

Shifa Tameer-e-Millat University
Rawalpindi Institute of Cardiology

Investigators

Principal Investigator: Nismat Javed, MBBS (2021), Shifa College of Medicine, Shifa Tameer-e-Millat University
Study Director: Jahanzeb Malik, MBBS (2011), Rawalpindi Institute of Cardiology
Study Chair: Adeel ur Rehman, MBBS, FCPS, Rawalpindi Institute of Cardiology