Colchicine for Coronary Artery Disease

(POPCORN Trial)

Recruiting at 6 trial locations

Overseen By Taj Kaur

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: VA Office of Research and Development

Must not be taking: Colchicine, Strong CYP3A4 inhibitors

Disqualifiers: Inflammatory bowel disease, Neuromuscular disease, Severe hepatic disease, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

700 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests colchicine, a medication known for reducing inflammation, to determine if it can lower the risk of heart problems, such as heart attacks and strokes, after major surgery in people with heart disease. The study aims to understand how inflammation affects the heart and blood vessels during recovery from surgery. Participants will receive either colchicine or a placebo (a pill with no active drug) to compare results. Suitable candidates for this trial have previously undergone heart procedures, like bypass surgery or stent placement, and are scheduled for major surgery. As a Phase 4 trial, this research seeks to understand how this already FDA-approved and effective treatment can benefit more patients.

Do I have to stop taking my current medications for this trial?

The trial does not specify if you need to stop all current medications. However, you cannot participate if you are on strong CYP3A4 and/or P-glycoprotein inhibitors like ritonavir, clarithromycin, diltiazem, or verapamil at the start. If you start these medications during the study, dose adjustments will be made. Also, avoid grapefruit juice while on the study drug.

What is the safety track record for colchicine?

Research has shown that colchicine is generally safe for people. Patients with heart conditions tolerate it well, and it has long been used to treat inflammatory diseases. Recent studies indicate that colchicine can help reduce heart-related issues without major safety concerns. Additionally, a study that combined results from multiple studies found colchicine safe for people with heart disease. While it may not lower the risk of death, it helps manage inflammation. Overall, colchicine has a strong safety record for those with coronary artery disease. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Unlike the standard treatments for coronary artery disease, which mainly involve lifestyle changes, medications like statins and beta-blockers, or surgical interventions, colchicine offers a unique approach. Researchers are excited about colchicine because it has strong anti-inflammatory properties that target inflammation in the arteries, which is a key contributor to coronary artery disease. This mechanism is different from traditional treatments that primarily focus on lowering cholesterol or managing blood pressure. By addressing inflammation directly, colchicine has the potential to improve outcomes in patients undergoing surgery for coronary artery disease more effectively and in a shorter timeframe.

What is the effectiveness track record for colchicine in reducing complications after major surgery?

Research has shown that colchicine, which participants in this trial may receive, can help lower the risk of heart problems by reducing inflammation in the arteries. In people with stable atherosclerosis, a condition where arteries are clogged with fatty deposits, taking a low dose of colchicine decreased major heart-related issues by 31%. Studies also indicate that colchicine effectively manages heart diseases linked to heart attacks and strokes. Although it does not significantly lower the risk of dying from heart disease, its ability to reduce inflammation makes it a promising option for preventing complications after surgery. Known for its safety and quick action, colchicine is a potentially valuable treatment for heart-related issues. ^{1 2 3 4 6}

Who Is on the Research Team?

Binita Shah, MD

Principal Investigator

VA NY Harbor Healthcare System, New York, NY

Are You a Good Fit for This Trial?

This trial is for men and women with a history of heart surgery or significant coronary artery disease, who are now facing intermediate- or high-risk surgeries. They must not have used colchicine recently, have inflammatory bowel issues, severe kidney or liver diseases, certain neuromuscular disorders, be pregnant/nursing/planning pregnancy, on specific drugs that interact with colchicine, or have an active infection.

Inclusion Criteria

I am having a minimally invasive surgery and have at least one heart or stroke risk factor.

I have had heart surgery or have significant heart artery disease and need a major surgery soon.

Exclusion Criteria

I have a progressive muscle or nerve disease like ALS or muscular dystrophy.

Participating in a competing study or unable to consent

If I start a new medication after surgery, I understand my dose may need adjustments.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-surgery Treatment

Participants receive a loading dose of colchicine or placebo one day before surgery

1 day

1 visit (in-person)

Post-surgery Treatment

Participants receive colchicine or placebo twice daily for 14 days post-operation

14 days

Daily administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

30 days

1 visit (in-person) at 30 days post-operation

What Are the Treatments Tested in This Trial?

Interventions

• Colchicine
• Placebo

Trial Overview

The POPCORN Trial is testing whether the anti-inflammatory medication colchicine can reduce complications like heart attack and stroke in patients with heart disease undergoing major surgery compared to a placebo (a substance with no therapeutic effect).

How Is the Trial Designed?

Group I: Colchicine Active Control 1 Intervention

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.

Group II: Placebo Placebo Group 1 Intervention

Matching placebo at same time points as active comparator

Colchicine is already approved in United States for the following indications:

Approved in United States as Colcrys for:

• Gout
• Familial Mediterranean Fever

Who Is Running the Clinical Trial?

VA Office of Research and Development

Lead Sponsor

Trials

1,691

Recruited

3,759,000+

NYU Grossman School of Medicine

Collaborator

Trials

5

Recruited

2,400+

NYU School of Medicine

Collaborator

Trials

3

Recruited

1,200+

Published Research Related to This Trial

A study involving patients with chronic coronary disease demonstrated that colchicine significantly reduced the risk of cardiovascular events, highlighting its potential as an effective treatment option.

The findings suggest that colchicine may work by reducing inflammation, which is a key factor in the progression of coronary disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-dose colchicine reduced risk for cardiovascular events in chronic coronary disease. Cohn, JN.[2021]

The LoDoCo2 trial is investigating the efficacy and safety of low-dose colchicine (0.5 mg daily) in 5522 patients with stable coronary artery disease, aiming to confirm its potential for secondary prevention of cardiovascular events.

This study is designed to detect a 30% reduction in major cardiovascular events, such as heart attacks and strokes, while also monitoring for any adverse effects related to colchicine, indicating a thorough approach to evaluating its safety and effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of low-dose colchicine in patients with stable coronary artery disease: The LoDoCo2 trial rationale, design, and baseline characteristics. Nidorf, SM., Fiolet, ATL., Eikelboom, JW., et al.[2023]

Colchicine, traditionally used for gout, has a unique anti-inflammatory mechanism that inhibits the NLRP3 inflammasome, reducing pro-inflammatory cytokines like IL-1β and IL-18, which are involved in coronary artery disease.

Long-term use of colchicine has been linked to a lower rate of cardiovascular events in both chronic and acute coronary syndromes, demonstrating its potential as a safe and effective treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Colchicine for acute and chronic coronary syndromes. Imazio, M., Andreis, A., Brucato, A., et al.[2021]

Low-dose colchicine significantly reduces the rate of major adverse cardiovascular events and acute coronary syndrome in patients with coronary artery disease, based on a review of 11,955 patients across multiple randomized controlled trials.

While colchicine is generally safe, it is associated with an increased risk of gastrointestinal events, highlighting the need for monitoring in patients receiving this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-Dose Colchicine in Coronary Artery Disease - Systematic Review and Meta-Analysis. Abrantes, AM., Nogueira-Garcia, B., Alves, M., et al.[2021]

The CHANCE-3 trial is investigating the efficacy of colchicine in preventing recurrent strokes in 8,238 patients with acute minor-to-moderate ischemic stroke or high-risk transient ischemic attack, aiming for a 25% reduction in stroke events within 3 months.

Colchicine will be administered for 90 days, and the study will also monitor for any adverse events related to the treatment, ensuring a comprehensive assessment of its safety and effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Colchicine in High-risk Patients with Acute Minor-to-moderate Ischemic Stroke or Transient Ischemic Attack (CHANCE-3): Rationale and design of a multicenter randomized placebo-controlled trial. Wang, Y., Li, J., Johnston, SC., et al.[2023]

In the LoDoCo2 trial involving 1776 participants over a median of 32.7 months, colchicine 0.5 mg daily significantly reduced the risk of cardiovascular events without adversely affecting renal function, as there were no changes in creatinine or blood urea nitrogen levels.

Colchicine was associated with mild elevations in liver enzymes (ALT) and creatine kinase (CK), but no severe elevations were observed, indicating that while there are some changes in liver and muscle markers, they are not clinically significant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effect of Years-Long Exposure to Low-Dose Colchicine on Renal and Liver Function and Blood Creatine Kinase Levels: Safety Insights from the Low-Dose Colchicine 2 (LoDoCo2) Trial. van Broekhoven, A., Mohammadnia, N., Silvis, MJM., et al.[2022]

In a review of six randomized controlled trials involving 6,005 post-acute myocardial infarction patients, colchicine did not significantly reduce cardiovascular mortality or recurrent heart attacks compared to a control group.

Colchicine was found to be safe, as it did not increase the risk of adverse events, including gastrointestinal issues, indicating that while it may not be effective for improving cardiovascular outcomes, it is not harmful to patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Colchicine in Post-acute Myocardial Infarction Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Diaz-Arocutipa, C., Benites-Meza, JK., Chambergo-Michilot, D., et al.[2021]

In the LoDoCo2 trial involving 5522 patients with chronic coronary disease, low-dose colchicine (0.5 mg daily) significantly reduced cardiovascular deaths without adversely affecting specific causes of death, indicating its safety in this context.

Most deaths during the study were due to non-cardiovascular causes, with age over 65 being a strong predictor of non-cardiovascular mortality, highlighting the role of comorbidities in overall mortality for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drivers of mortality in patients with chronic coronary disease in the low-dose colchicine 2 trial. Opstal, TSJ., Nidorf, SM., Fiolet, ATL., et al.[2023]

Colchicine treatment in patients with coronary artery disease significantly reduces the risk of composite events such as myocardial infarction and restenosis after percutaneous coronary intervention, with an odds ratio of 0.48 based on a meta-analysis of 10 trials involving 6398 patients.

While colchicine shows promise in lowering the risk of heart-related events, it does not improve all-cause mortality and is associated with a higher risk of gastrointestinal side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug repurposing? Cardiovascular effect of colchicine on patients with coronary artery disease: A systematic review and meta-analysis. Tien, YY., Huang, HK., Shih, MC., et al.[2021]

Citations

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pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/41019029/

Efficacy and safety of colchicine in patients with coronary ...

Conclusion: Colchicine does not reduce the relative risk of all-cause and cardiovascular death in patients with CAD. However, it can reduce the ...

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sciencedirect.com

sciencedirect.com/science/article/pii/S2666602225001132

Efficacy and safety of colchicine in patients with coronary ...

Our results demonstrate no significant reduction in all-cause or cardiovascular mortality with colchicine. This is an important finding as it ...

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nejm.org

nejm.org/doi/full/10.1056/NEJMoa2021372

Colchicine in Patients with Chronic Coronary Disease

Evidence from a recent trial has shown that the antiinflammatory effects of colchicine reduce the risk of cardiovascular events in patients with recent ...

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jacc.org

jacc.org/doi/10.1016/j.jacc.2023.05.055

Low-Dose Colchicine for Secondary Prevention of ...

Low-dose colchicine (0.5 mg/d orally) has been shown to safely lower major adverse cardiovascular events by 31% among those with stable atherosclerosis and by ...

5.

ahajournals.org

ahajournals.org/doi/10.1161/ATVBAHA.124.319851

Colchicine's Role in Cardiovascular Disease Management

Randomized clinical trials established low-dose colchicine as an effective treatment for pericarditis and atherosclerotic cardiovascular disease ...

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academic.oup.com

academic.oup.com/eurheartj/article/46/26/2552/8123897

Long-term trials of colchicine for secondary prevention of ...

Overall, the pooled results from the present meta-analysis further demonstrates that colchicine is safe to use in patients with atherosclerotic ...