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

CARA-003-22S

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.

2023-08-01

2027-07-31

2028-04-30

Recruiting

Early phase I

700

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

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE4'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'interventionModelDescription': '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. If a patient is unable to take oral medications (by mouth or nasogastric tube) post-operatively (e.g., post abdominal surgery), colchicine will be held until the clinically treating physician allows resumption of oral medications if still within 14 days post-operation.', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'QUADRUPLE', 'maskingDescription': 'Matching placebo at the same time points as the intervention', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR']}}, 'enrollmentInfo': {'count': 700, 'type': 'ESTIMATED'}}

2023-08-03