The Peri-OPerative COlchicine to Reduce Negative Events (POPCORN) Trial (POPCORN)

April 21, 2026 updated by: VA Office of Research and Development

Impact of Colchicine on Peri-Operative Major Adverse Cardiovascular Events in Patients With Prior Coronary Revascularization

Heart disease remains the leading cause of death in Veterans. Inflammation in the arteries of the heart may increase the risk of cardiac death. Patients with heart disease undergoing major surgery are at increased risk of complications after surgery, including heart attack, stroke, and death. The proposed research seeks to better understand the role of inflammation in the damage to the heart and blood vessels after major surgery. This research also seeks to identify the potential beneficial role of a safe medication, colchicine, which has direct effects on inflammatory cells and has been used in the treatment of inflammatory diseases for more than 2000 years, on reducing the rate of complications after surgery. With its quick onset of action and excellent safety profile, colchicine may have the potential to reduce risk of heart injury, stroke, or death after major surgery.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Patients with prior coronary revascularization have a high risk of major adverse cardiovascular events (MACE) after major surgery, up to more than 2-fold when compared to patients without prior coronary revascularization. The pro-inflammatory and hypercoagulable states induced by surgery and the hemodynamic changes caused by fluid shifts and anesthesia are all important triggers of perioperative myocardial ischemia. Indeed, peri-operative systemic inflammation is associated with a nearly 4-fold increase in the risk of perioperative MACE. Neutrophils, the most abundant of inflammatory cells, adhere to inflamed or injured endothelium, migrate into the vessel wall, release proteolytic enzymes that can lead to erosion or rupture of plaque. Peri-operative cytokine generation may also activate the inflammasome and, thereby, macrophage-mediated synthesis of interleukin (IL)-1 , a known target for therapy for secondary prevention of MACE, particularly in the setting of high C-reactive protein (CRP) concentration.

Colchicine is a safe, well-tolerated anti-inflammatory agent that preferentially accumulates in neutrophils compared with other inflammatory cells. Colchicine inhibits chemotaxis, endothelial adhesion, and extravasation of neutrophils at sites of endothelial injury or inflammation; suppresses the inflammasome-mediated production of IL-1 by macrophages; and reduces inflammation and MACE in patients with cardiovascular disease. The Colchicine Cardiovascular Outcomes Trial and Low Dose Colchicine 2 Trial demonstrated a reduction in MACE with colchicine in about 4000 patients with prior myocardial infarction and about 5000 patients with stable coronary artery disease, respectively. The Colchicine-PCI trial demonstrated for the first time that administration of colchicine prior to injury dampens the inflammatory response measured by CRP. The effects of colchicine on peri-operative MACE in patients with prior coronary revascularization or high coronary atherosclerotic burden undergoing major surgery, remains unknown.

The aims of this trial are to 1) assess the effect of colchicine compared to placebo on peri-operative MACE in response to intermediate- or high-risk non-cardiac surgery in patients with prior coronary revascularization or high coronary atherosclerotic burden; 2) characterize the level of systemic inflammation and profile of peri-operative neutrophils in this population; and 3) determine the clinical and genetic predictors of peri-operative MACE and examine factors that determine heterogeneity of treatment response in this population. This prospective, double-blinded, placebo-controlled, randomized trial will enroll 700 participants with prior coronary revascularization or high coronary atherosclerotic burden who undergo intermediate- or high-risk non-cardiac surgery across six VA medical centers that serve as cardiovascular referral centers for their VISNs. Following referral for surgery, and confirmation that the patient meets all study entry criteria, participants will be consented and randomized 1:1 within center to a loading dose of colchicine or placebo one day before surgery and twice daily dosing for 14 days post-operation. DNA will be collected at baseline, while measures of systemic inflammation will be collected at baseline, one day, two days, and at 14 days post-operation (or hospital discharge, whichever occurs earlier). Follow-up for all randomized participants who undergo surgery will occur at 30 days + 7 days.

Study Type

Interventional

Enrollment (Estimated)

700

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35233-1927
    • California
      • Long Beach, California, United States, 90822
    • Florida
      • Gainesville, Florida, United States, 32608-1135
    • New York
      • Buffalo, New York, United States, 14215-1129
      • New York, New York, United States, 10010-5011
        • Recruiting
        • VA NY Harbor Healthcare System, New York, NY
        • Contact:
        • Principal Investigator:
          • Binita Shah, MD
        • Contact:
    • North Carolina
    • Ohio
      • Cleveland, Ohio, United States, 44106-1702
    • Texas
      • Dallas, Texas, United States, 75216-7167
      • Houston, Texas, United States, 77030-4211

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

Men and women with

  • Prior coronary revascularization (via PCI or coronary artery bypass graft surgery) or high coronary atherosclerotic burden (>70% let main disease or >80% disease in the proximal or mid LAD, prox Cx, or prox or mid RCA on coronary angiography), AND
  • Referred for intermediate- or high-risk surgery (general abdominal or intraperitoneal surgery, neurosurgery, suprainguinal surgery, peripheral vascular surgery, thoracic surgery).
  • If planned for only a laparoscopic or endovascular approach (this includes a minimally invasive hybrid approach such as transcarotid artery revascularization), at least one component of the Revised Cardiac Risk Index score (history of myocardial infarction, history of congestive heart failure, history of transient ischemic attack or stroke, pre-operative use of insulin, pre-operative creatinine >2 mg/dL) should be present.

Exclusion Criteria:

  • Colchicine use within one month or history of colchicine intolerance
  • Inflammatory bowel disease with history of diarrhea as presentation or chronic diarrhea

  • Pre-existent progressive neuromuscular disease

    • amyotrophic lateral sclerosis
    • hereditary muscular disorders
    • myositis
    • necrotizing myopathy
    • myasthenia gravis
    • lambert-eaton syndrome
  • Glomerular filtration rate <30mL/minute or on dialysis
  • History of cirrhosis, chronic active hepatitis or severe hepatic disease
  • History of myelodysplasia with current evidence of cytopenia
  • Active infection defined as fever >100.4oF or antibiotic use with white blood cell count greater than the upper limit of normal or lower than the lower limit of normal within 24 hours of randomization (major confounder with increased inflammatory markers)
  • Undergoing immunosuppressive or immunostimulatory chemo or biologic therapy
  • Pregnant (as confirmed by urine or serum test), nursing, or planning to become pregnant during study participation
  • Participating in a competing study or unable to consent
  • Any significant condition or situation that may put the participant at higher risk, confound the study results, or interfere with adherence to study procedures

  • Patients on strong CYP3A4 and/or P-glycoprotein inhibitors (e.g., ritonavir, clarithromycin, diltiazem, verapamil) at baseline will also be excluded due to potential drug interactions

    • However, if one of these medications are started during the post-operative study period, dose adjustments will be made per drug package insert
    • Participants will also be instructed not to drink grapefruit juice while on study drug

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Colchicine
One day before surgery: Colchicine 1.2 mg with 0.6 mg PO one hour later. This load will be followed by colchicine 0.6 mg twice daily for a total of 14 days.
Drug: Colchicine
0.6 mg tablets
Other Names:
  • Colcrys
Placebo Comparator: Placebo
Matching placebo at same time points as active comparator
Drug: Placebo
Matching placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Major adverse cardiovascular events
Time Frame: 30 days post-operation
Defined as a composite rate of myocardial injury, non-fatal MI, non-fatal stroke, and all-cause mortality.
30 days post-operation

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
rate of myocardial injury
Time Frame: 30 days post-operation
rate of myocardial injury
30 days post-operation
rate of non-fatal MI
Time Frame: 30 days post-operation
rate of non-fatal MI
30 days post-operation
rate of non-fatal stroke
Time Frame: 30 days post-operation
rate of non-fatal stroke
30 days post-operation
rate of all-cause mortality
Time Frame: 30 days post-operation
rate of all-cause mortality
30 days post-operation
Unplanned coronary revascularization
Time Frame: 30 days post-operation
Unplanned coronary revascularization
30 days post-operation
Prognostic threshold of myocardial injury
Time Frame: 30 days post-operation
troponin >30 ng/L (high-sensitivity troponin >65 ng/L or absolute change >14 ng/L or 20-65 ng/L with an absolute change of >5 ng/L)
30 days post-operation
Change in hsCRP
Time Frame: through 14 days post-operation or at hospital discharge, whichever occurs earlier
between 1) baseline and one day post-operation, and 2) over time including at two days and 14 days post-operation (or hospital discharge, whichever occurs earlier)
through 14 days post-operation or at hospital discharge, whichever occurs earlier

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

VA Office of Research and Development

Collaborators

NYU Langone Health

Investigators

  • Principal Investigator: Binita Shah, MD, VA NY Harbor Healthcare System, New York, NY

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 21, 2023

Primary Completion (Estimated)

July 31, 2028

Study Completion (Estimated)

April 30, 2029

Study Registration Dates

First Submitted

November 3, 2022

First Submitted That Met QC Criteria

November 15, 2022

First Posted (Actual)

November 16, 2022

Study Record Updates

Last Update Posted (Actual)

April 22, 2026

Last Update Submitted That Met QC Criteria

April 21, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CARA-003-22S
  • I01CX002358-01A2 (U.S. NIH Grant/Contract: VA Office of Research and Development)

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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