Clinical trial NCT04218786: Effect of Colchicine in Patients With Myocardial Infarction
Official title: Outcomes of Low-dose Colchicine in Patients With Myocardial Infarction: A Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Myocardium; Injury
Myocardial Infarction
Myocardial Ischemia
Keywords: colchicine; outcome: myocardial infarction
Lead sponsor: Shifa Tameer-e-Millat University
Sponsor class: OTHER
Collaborators: name: Rawalpindi Institute of Cardiology
First posted: 2020-01-06
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: 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

Primary outcomes:
measure: Major cardiovascular adverse events (number of events)
timeFrame: 3 months
Secondary outcomes:
measure: Troponin I (ng/ml)
timeFrame: 3 months
measure: Creatine Kinase-Myocardial Band (IU/L)
timeFrame: 3 months
measure: C-reactive protein (mg/L)
timeFrame: 3 months
Other outcomes:
Locations:
city: Rawalpindi
country: Pakistan
facility: Rawalpindi Institute of Cardiology
Study officials:
affiliation: Shifa College of Medicine, Shifa Tameer-e-Millat University
name: Nismat Javed, MBBS (2021)
role: PRINCIPAL_INVESTIGATOR
affiliation: Rawalpindi Institute of Cardiology
name: Jahanzeb Malik, MBBS (2011)
role: STUDY_DIRECTOR
affiliation: Rawalpindi Institute of Cardiology
name: Adeel ur Rehman, MBBS, FCPS
role: STUDY_CHAIR
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