Colchicine in Percutaneous Coronary Intervention

Study Overview
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Brief Summary
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Inflammation in the arteries of the heart may increase the risk of cardiac death. The proposed research seeks to identify the potential beneficial role of a safe anti-inflammatory medication, colchicine, on reducing damage caused by opening up a blockage in the arteries of the heart. With its quick onset of action and excellent safety profile, colchicine may have the potential to reduce risk of major adverse events related to the heart. This research also seeks to better understand the role of neutrophils, the most common type of inflammatory white blood cell in the body, when there is damage to the heart.

Detailed Description
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The investigators will use colchicine as a tool to elucidate the role of neutrophil activation during acute vascular injury, and to explore the association between neutrophil activation and adverse cardiovascular outcomes. Colchicine reduces cell surface expression of selections, adhesion molecules key to neutrophil recruitment after vascular injury. Daily colchicine use is associated with reduced adverse cardiovascular events in stable atherosclerosis. Using a clinical percutaneous coronary intervention (PCI) model, the investigators evaluate whether pre-procedural colchicine (1.8 mg oral load over one hour) reduces the rate of post-PCI adverse cardiovascular outcomes in the context of a double-blind placebo-controlled randomized study. The investigators will also characterize neutrophil biology in acute vascular injury and the effects of colchicine on neutrophil biology in this setting.

Official Title
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Anti-inflammatory Therapy During Percutaneous Coronary Intervention

Conditions
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Coronary Artery Disease, Acute Coronary Syndrome

Intervention / Treatment
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* Drug: Colchicine vs Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Referred for possible PCI Exclusion Criteria: Colchicine use within 1 month History of colchicine intolerance Glomerular filtration rate <30mL/minute or on dialysis (due to the need to adjust colchicine dose in this setting) Active malignancy or infection (major confounder with increased inflammatory markers) History of myelodysplasia (due to suggested cautionary use of colchicine in this setting) High-dose statin load <24 hours prior to procedure (major confounder that is known to reduce inflammatory levels in 12 to 24 hours) Use of anti-inflammatory agents (except aspirin) within 5 halflives of the individual drug Use of strong Cytochrome P450, Family 3, Subfamily A, Polypeptide 4 (CYP3A4) and/or P-glycoprotein inhibitors (e.g. ritonavir, ketoconazole, clarithromycin, cyclosporine, diltiazem and verapamil, again due to drug interactions) Unable to consent Participating in a competing study Any significant condition or situation that may put the subject at higher risk, confound the study results or interfere with adherence to study procedures

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Colchicine<br>Colchicine 1.8 mg PO over 1 hour | Drug: Colchicine vs Placebo<br>* Colchicine vs Placebo 1.8 mg PO over 1 hour<br>|
| Placebo Comparator: Placebo<br>Matching placebo | Drug: Colchicine vs Placebo<br>* Colchicine vs Placebo 1.8 mg PO over 1 hour<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Peri-procedural Myocardial Necrosis | troponin above the upper limit of normal (ULN) | 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With All-cause Mortality, Non-fatal MI, or Target Vessel Revascularization (TVR) | all-cause mortality, non-fatal MI (universal definition), or target vessel revascularization (TVR) | 30 days | 
| Number of Participants With All-cause Mortality, Non-fatal MI, or TVR | all-cause mortality, non-fatal MI (universal definition), or target vessel revascularization (TVR) | 1 year | 
| All-cause Mortality, Non-fatal MI, or TVR | all-cause mortality, non-fatal MI (universal definition), or target vessel revascularization (TVR) | 2 years | 
| All-cause Mortality, Non-fatal MI, or TVR | all-cause mortality, non-fatal MI (universal definition), or target vessel revascularization (TVR) | 3 years | 
| All-cause Mortality, Non-fatal MI, or TVR | all-cause mortality, non-fatal MI (universal definition), or target vessel revascularization (TVR) | 4 years | 
| All-cause Mortality, Non-fatal MI, or TVR | all-cause mortality, non-fatal MI (universal definition), or target vessel revascularization (TVR) | 5 years | 
| Number of Participants With Peri-procedural Myocardial Infarction (MI) | SCAI definition | 24 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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inflammation, percutaneous coronary intervention, coronary artery disease, colchicine