Clinical trial NCT02594111: Colchicine in Percutaneous Coronary Intervention
Official title: Anti-inflammatory Therapy During Percutaneous Coronary Intervention
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Coronary Artery Disease
Acute Coronary Syndrome
Keywords: inflammation
percutaneous coronary intervention
coronary artery disease
colchicine
Lead sponsor: VA Office of Research and Development
Sponsor class: FED
Collaborators: name: NYU Langone Health
First posted: 2015-11-01
Enrollment: 714
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants With Peri-procedural Myocardial Necrosis
timeFrame: 24 hours
Secondary outcomes:
measure: Number of Participants With All-cause Mortality, Non-fatal MI, or Target Vessel Revascularization (TVR)
timeFrame: 30 days
measure: Number of Participants With All-cause Mortality, Non-fatal MI, or TVR
timeFrame: 1 year
measure: All-cause Mortality, Non-fatal MI, or TVR
timeFrame: 2 years
measure: All-cause Mortality, Non-fatal MI, or TVR
timeFrame: 3 years
measure: All-cause Mortality, Non-fatal MI, or TVR
timeFrame: 4 years
measure: All-cause Mortality, Non-fatal MI, or TVR
timeFrame: 5 years
measure: Number of Participants With Peri-procedural Myocardial Infarction (MI)
timeFrame: 24 hours
Other outcomes:
Locations:
city: New York
country: United States
facility: Manhattan Campus of the VA NY Harbor Healthcare System, New York, NY
state: New York
Study officials:
affiliation: Manhattan Campus of the VA NY Harbor Healthcare System, New York, NY
name: Binita Shah, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Shah B, Pillinger M, Zhong H, Cronstein B, Xia Y, Lorin JD, Smilowitz NR, Feit F, Ratnapala N, Keller NM, Katz SD. Effects of Acute Colchicine Administration Prior to Percutaneous Coronary Intervention: COLCHICINE-PCI Randomized Trial. Circ Cardiovasc Interv. 2020 Apr;13(4):e008717. doi: 10.1161/CIRCINTERVENTIONS.119.008717. Epub 2020 Apr 16.