Colchicine in Percutaneous Coronary Intervention (Colchicine-PCI)

Anti-inflammatory Therapy During Percutaneous Coronary Intervention

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.

Study Overview

• Status: Completed
• Conditions: Coronary Artery Disease; Acute Coronary Syndrome
• Intervention / Treatment: Drug: Colchicine vs Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 714
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10010
      • Manhattan Campus of the VA NY Harbor Healthcare System, New York, NY

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Matching placebo	Drug: Colchicine vs Placebo; Colchicine vs Placebo 1.8 mg PO over 1 hour
Active Comparator: Colchicine; Colchicine 1.8 mg PO over 1 hour	Drug: Colchicine vs Placebo; Colchicine vs Placebo 1.8 mg PO over 1 hour

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: VA Office of Research and Development
• Collaborators: NYU Langone Health
• Investigators: Principal Investigator: Binita Shah, MD, Manhattan Campus of the VA NY Harbor Healthcare System, New York, NY

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): May 30, 2013
• Primary Completion (Actual): August 30, 2019
• Study Completion (Actual): December 31, 2021

Study Registration Dates

• First Submitted: October 30, 2015
• First Submitted That Met QC Criteria: October 30, 2015
• First Posted (Estimate): November 1, 2015

Study Record Updates

• Last Update Posted (Estimate): February 20, 2023
• Last Update Submitted That Met QC Criteria: January 25, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: percutaneous coronary intervention; coronary artery disease; inflammation; colchicine
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Acute Coronary Syndrome; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Gout Suppressants; Colchicine
• Other Study ID Numbers: CARB-025-15S

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes