None listed
Conditions
Brief summary
AIMS: The aim of the vanguard Co-POC trial is to assess the safety and feasibility of the trial protocol and to obtain important preliminary data on the effect that colchicine 0.5mg once daily for up to 3 days pre-operatively and 30 days post-operatively has on the incidence and extent of post-operative myocardial injury after coronary artery bypass graft (CABG) surgery. DESIGN AND METHODS: The Co-POC vanguard trial is a RCT of colchicine v placebo nested in the Australian VISION Cardiac Surgery cohort. Eligible patients recruited into the VISION Cardiac Surgery study who are undergoing isolated coronary artery bypass graft surgery will be offered the opportunity to participate in the vanguard Co-POC trial. We will recruit 204 patients into this pilot trial (1:1 recruitment). Patients will be randomised to colchicine 0.5mg once daily or matching placebo. Treatment will be commenced 3 days prior to surgery (but can be commenced up to 24 hours pre-operatively if necessary) and will be continued for 1 month after surgery. Medications will be provided by Aspen Pharmacare Australia according to the US Food and Drug Administration current good manufacturing practice regulations. All concomitant medications will be provided at the discretion of treating clinicians and in keeping with clinical guidelines. Patients will have blood samples collected for hs-cTnI <4 hours pre-operatively and post-operatively at 6-12 hours and on days 1 to 3 (in keeping with the VISION Cardiac Surgery protocol). Analysis plan: All analyses will be by intention to treat. Groups will be compared using the Mann-Whitney U and chi-square tests as appropriate. Kaplan Meier curves will be used to demonstrate event free survival and groups compared using the log-rank test.
Interventions
Patients will be randomized to receive either a placebo or colchicine commenced between 24 and 72 hours prior to surgery, decided at the clinical discretion of the treating physician. and continued for 1 month after surgery. Colchicine/placebo will be given as 0.5 mg once daily without a loading dose. Colchicine/placebo will be provided by gastric tube in unconscious postoperative patients in intensive care units. Adherence will be determined on the basis of counts of pills in dispensed boxes w
Patients will be randomized to receive either a placebo or colchicine commenced between 24 and 72 hours prior to surgery, decided at the clinical discretion of the treating physician. and continued for 1 month after surgery. Colchicine/placebo will be given as 0.5 mg once daily without a loading dose. Colchicine/placebo will be provided by gastric tube in unconscious postoperative patients in intensive care units. Adherence will be determined on the basis of counts of pills in dispensed boxes with a target of at least 80% adherence. Blood samples will be taken prior to and up to 3 days after coronary artery bypass surgery. They will then have one routine follow-up at 6 weeks to have a physical examination, an ECG and an echocardiogram.
Sponsors
Sydney Local Health District
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Prevention
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
a) Eligible and have consented to participate in the Vascular Events In Surgery patIents cOhort evaluatioN - Cardiac Surgery study (an observational study of patients undergoing major cardiac surgery: NCT01842568 study), and b) undergoing isolated coronary artery bypass grafting (CABG)
Exclusion criteria
1) Known intolerance of colchicine 2) Pre-existing or planned peri-operative colchicine treatment 3) Known myopathy (or elevated creatine kinase> 3 x upper limit of normal) 4) Severe liver disease (or aminotransferase level >1.5 upper limit of normal) 5) Severe blood dyscrasia (white cell count or platelet count < lower limit of normal) 6) Inflammatory bowel disease 7) Estimated glomerular filtration rate <45mL/min per 1.73m2 8) Women of childbearing potential 9) Scheduled for valve and/or aortic surgery in addition to CABG. 10) Therapy with a strong CYP3A4 inhibitor (e.g. cyclosporine, ritonavir, clarithromycin or ketoconazole) or inducer (eg rifampicin)
Outcome results
None listed