Colchicine for Coronary Artery Disease
(POPCORN Trial)
Recruiting in Palo Alto (17 mi)
+6 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 4
Recruiting
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
Approved in 1 Jurisdiction
Trial Summary
What is the purpose of this trial?This trial tests colchicine, an anti-inflammatory medication, on patients with previous heart surgeries undergoing major non-heart surgeries. The aim is to see if colchicine can reduce the risk of heart attacks and strokes by lowering inflammation. Colchicine has been shown to reduce the risk of cardiovascular events in patients with coronary artery disease due to its anti-inflammatory properties.
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 data supports the idea that Colchicine for Coronary Artery Disease is an effective drug?
The available research shows that colchicine is effective in reducing the risk of cardiovascular events in patients with coronary artery disease. For example, the LoDoCo2 trial found that low-dose colchicine significantly reduced the risk of heart-related problems like heart attacks and strokes in patients with stable coronary artery disease. Additionally, a systematic review and meta-analysis confirmed colchicine's protective effects for patients with coronary artery disease. These studies suggest that colchicine can be a beneficial addition to existing treatments for coronary artery disease.
12345What safety data exists for colchicine in treating coronary artery disease?
The LoDoCo2 trial and other studies have evaluated the safety of low-dose colchicine (0.5 mg daily) in patients with coronary artery disease. The LoDoCo2 trial found that colchicine is generally safe, with potential adverse events including gastrointestinal intolerance, neuropathy, myopathy, myositis, and neutropenia. A systematic review and meta-analysis confirmed an increased risk of gastrointestinal events but no significant increase in other adverse events. Another study found no significant impact on renal or liver function or creatine kinase levels after 2-4 years of colchicine use. Overall, colchicine is considered safe for long-term use in this patient population, with gastrointestinal issues being the most common side effect.
35678Is the drug Colchicine a promising treatment for coronary artery disease?
Yes, Colchicine is a promising treatment for coronary artery disease. It has been shown to reduce the risk of heart-related events in patients with this condition. Colchicine is an anti-inflammatory drug that can help prevent heart attacks and strokes by reducing inflammation in the arteries. It is also affordable and has a good safety profile, making it a valuable option for treating coronary artery disease.
23459Eligibility Criteria
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.
+11 more
Trial Timeline
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
Participant Groups
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).
2Treatment groups
Active Control
Placebo Group
Group I: ColchicineActive Control1 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: PlaceboPlacebo Group1 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Birmingham VA Medical Center, Birmingham, ALBirmingham, AL
VA NY Harbor Healthcare System, New York, NYNew York, NY
Durham VA Medical Center, Durham, NCDurham, NC
Louis Stokes VA Medical Center, Cleveland, OHCleveland, OH
More Trial Locations
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Who Is Running the Clinical Trial?
VA Office of Research and DevelopmentLead Sponsor
NYU Grossman School of MedicineCollaborator
NYU School of MedicineCollaborator
References
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. [2023]Anti-inflammatory therapy using colchicine has reduced recurrent vascular events in patients with coronary heart disease.
Low-dose colchicine reduced risk for cardiovascular events in chronic coronary disease. [2021]Label="SOURCE CITATION">Nidorf SM, Fiolet ATL, Mosterd A, et al. Colchicine in patients with chronic coronary disease. N Engl J Med. 2020;383:1838-47. 32865380.
The effect of low-dose colchicine in patients with stable coronary artery disease: The LoDoCo2 trial rationale, design, and baseline characteristics. [2023]Because patients with stable coronary artery disease are at continued risk of major atherosclerotic events despite effective secondary prevention strategies, there is a need to continue to develop additional safe, effective and well-tolerated therapies for secondary prevention of cardiovascular disease. RATIONALE AND DESIGN: The LoDoCo (Low Dose Colchicine) pilot trial showed that the anti-inflammatory drug colchicine 0.5 mg once daily appears safe and effective for secondary prevention of cardiovascular disease. Colchicine's low cost and long-term safety suggest that if its efficacy can be confirmed in a rigorous trial, repurposing it for secondary prevention of cardiovascular disease would have the potential to impact the global burden of cardiovascular disease. LoDoCo2 is an investigator-initiated, international, multicentre, double-blind, event driven trial in which 5522 patients with stable coronary artery disease tolerant to colchicine during a 30-day run-in phase have been randomized to colchicine 0.5 mg daily or matching placebo on a background of optimal medical therapy. The study will have 90% power to detect a 30% reduction in the composite primary endpoint: cardiovascular death, myocardial infarction, ischemic stroke and ischemia-driven coronary revascularization. Adverse events potentially related to the use of colchicine will also be collected, including late gastrointestinal intolerance, neuropathy, myopathy, myositis, and neutropenia. CONCLUSION: The LoDoCo2 Trial will provide information on the efficacy and safety of low-dose colchicine for secondary prevention in patients with stable coronary artery disease.
Drug repurposing? Cardiovascular effect of colchicine on patients with coronary artery disease: A systematic review and meta-analysis. [2021]Patients with coronary artery disease (CAD) are at high risk of atherosclerotic events. The aim of this meta-analysis is to evaluate the cardiovascular protective effect of colchicine on patients with CAD.
Drivers of mortality in patients with chronic coronary disease in the low-dose colchicine 2 trial. [2023]Low-dose colchicine significantly reduces the risk of cardiovascular events in patients with chronic coronary disease. An increase of non-cardiovascular death raised concerns about its safety. This study reports cause-specific mortality and baseline predictors of mortality in the Low-Dose Colchicine 2 (LoDoCo2) trial.
Low-Dose Colchicine in Coronary Artery Disease - Systematic Review and Meta-Analysis. [2021]Background: Recent studies have revealed the benefits of using colchicine, a drug with anti-inflammatory properties, in coronary artery disease (CAD). This study systematically reviewed the benefits and risks of low-dose colchicine in patients with CAD. Methods and Results: We searched for randomized controlled trials (RCTs) in MEDLINE, the Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science databases (March 2020). Efficacy and safety outcomes were evaluated. Estimates are expressed as risk ratios (RRs) and 95% confidence intervals (95% CIs). Heterogeneity was assessed with I2 test. Confidence in the pooled evidence was appraised using the GRADE framework. Colchicine reduced the rate of major adverse cardiovascular events (RR 0.65; 95% CI 0.49-0.86; 6 RCTs; I2=50%; 11,718 patients; GRADE, moderate confidence), acute coronary syndrome (RR 0.64; 95% CI 0.46-0.90; I2=47%; 7 RCTs; 11,955 patients; GRADE, very low confidence), stroke (RR 0.49; 95% CI 0.30-0.78; I2=0%; 6 RCTs; 11,896 patients; GRADE, moderate confidence), and cardiovascular interventions (RR 0.61; 95% CI 0.42-0.89; I2=40%; 4 RCTs; 11,284 patients; GRADE, high confidence). Colchicine did not increase the risk of adverse events, except for gastrointestinal events (RR 1.54; 95% CI 1.11-2.13; I2=72%; 9 RCTs; 12,374 patients; GRADE, very low confidence). Conclusions: Low-dose colchicine in patients with CAD is associated with beneficial effects on prognosis, although an increased risk of gastrointestinal events was confirmed.
Efficacy and Safety of Colchicine in Post-acute Myocardial Infarction Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. [2021]Background: Inflammation plays a key role in atherosclerotic plaque destabilization and adverse cardiac remodeling. Recent evidence has shown a promising role of colchicine in patients with coronary artery disease. We evaluated the efficacy and safety of colchicine in post-acute myocardial infarction (MI) patients. Methods: We searched five electronic databases from inception to January 18, 2021, for randomized controlled trials (RCTs) evaluating colchicine in post-acute MI patients. Primary outcomes were cardiovascular mortality and recurrent MI. Secondary outcomes were all-cause mortality, stroke, urgent coronary revascularization, levels of follow-up high-sensitivity C-reactive protein (hs-CRP), and drug-related adverse events. All meta-analyses used inverse-variance random-effects models. Results: Six RCTs involving 6,005 patients were included. Colchicine did not significantly reduce cardiovascular mortality [risk ratio (RR), 0.91; 95% confidence interval (95% CI), 0.52-1.61; p = 0.64], recurrent MI (RR, 0.87; 95% CI, 0.62-1.22; p = 0.28), all-cause mortality (RR, 1.06; 95% CI, 0.61-1.85; p = 0.78), stroke (RR, 0.28; 95% CI, 0.07-1.09; p = 0.05), urgent coronary revascularization (RR, 0.46; 95% CI, 0.02-8.89; p = 0.19), or decreased levels of follow-up hs-CRP (mean difference, -1.95 mg/L; 95% CI, -12.88 to 8.98; p = 0.61) compared to the control group. There was no increase in any adverse events (RR, 0.97; 95% CI, 0.89-1.07; p = 0.34) or gastrointestinal adverse events (RR, 2.49; 95% CI, 0.48-12.99; p = 0.20). Subgroup analyses by colchicine dose (0.5 vs. 1 mg/day), time of follow-up (<1 vs. ≥1 year), and treatment duration (≤30 vs. >30 days) showed no changes in the overall findings. Conclusion: In post-acute MI patients, colchicine does not reduce cardiovascular or all-cause mortality, recurrent MI, or other cardiovascular outcomes. Also, colchicine did not increase drug-related adverse events.
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. [2022]The Low-Dose Colchicine-2 (LoDoCo2) trial showed that 2-4 years exposure to colchicine 0.5 mg once daily reduced the risk of cardiovascular events in patients with chronic coronary artery disease. The potential effect of years-long exposure to colchicine on renal or liver function and creatine kinase (CK) has not been systematically evaluated and was investigated in this LoDoCo2 substudy.
Colchicine for acute and chronic coronary syndromes. [2021]Colchicine is an ancient drug, traditionally used for the treatment and prevention of gouty attacks; it has become standard of treatment for pericarditis with a potential role in the treatment of coronary artery disease. Atherosclerotic plaque formation, progression, destabilisation and rupture are influenced by active proinflammatory cytokines interleukin (IL)-1β and IL-18 that are generated in the active forms by inflammasomes, which are cytosolic multiprotein oligomers of the innate immune system responsible for the activation of inflammatory responses. Colchicine has a unique anti-inflammatory mechanism: it is not only able to concentrate in leucocytes, especially neutrophils, and block tubulin polymerisation, affecting the microtubules assembly, but also inhibits (NOD)-like receptor protein 3 (NLRP3) inflammasome. On this basis, colchicine interferes with several functions of leucocytes and the assembly and activation of the inflammasome as well, reducing the production of interleukin 1β and interleukin 18. Long-term use of colchicine has been associated with a reduced rate of cardiovascular events both in chronic and acute coronary syndromes, with an overall good safety profile. This review will focus on the influence of colchicine on the pathophysiology of coronary artery disease, reviewing essential pharmacology and discussing the most important and recent clinical studies. On the basis of current literature, colchicine is emerging as a possible new valuable, safe and cheap agent for the treatment of acute and chronic coronary syndromes.