The Metformin in Coronary Artery Bypass Graft (CABG) (MetCAB) Trial

Study Overview
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Brief Summary
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Rationale: In patients with a myocardial infarction, occlusion of a coronary artery induces myocardial ischemia and cell death. If untreated, the area of myocardium exposed to this interruption in blood supply, will largely become necrotic. The only way to limit final infarct size, is timely reperfusion of the occluded artery. Paradoxically, however, reperfusion itself can also damage myocardial tissue and contribute to the final infarct size (reperfusion injury). Also during coronary artery bypass grafting (CABG), the myocardium is exposed to ischemia and reperfusion, which will induce cell death. Indeed, postoperatively, the plasma concentration of troponin I, a marker of cardiac necrosis, is increased, and associated with adverse outcome. The anti-hyperglycaemic drug metformin has been shown in preclinical studies to be able to reduce ischemia-reperfusion injury and to limit myocardial infarct size. Moreover, metformin therapy improves cardiovascular prognosis in patients with diabetes mellitus. Paradoxically, in patients with diabetes, current practice is to temporarily stop metformin before major surgery for the presumed risk of lactic acidosis, which is a rare complication of metformin. However, here is no evidence that this practice benefits the patient. The investigators hypothesize that pretreatment with metformin can reduce myocardial injury in patients undergoing elective CABG surgery

Official Title
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The Metformin in CABG (MetCAB) Trial

Conditions
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Cardiovascular Disease, Ischemic Heart Disease

Intervention / Treatment
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* Drug: Metformin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Acceptation for CABG with or without concomitant valve surgery Informed consent Age ≥ 18 years Exclusion Criteria: Diabetes mellitus Renal dysfunction (MDRD < 60 ml/min) Elevated liver enzymes (ALAT > 3 times upper limit of reference range) Treatment with dipyridamole or xanthine derivatives Recent myocardial infarction (<2 weeks before inclusion) Off-pump surgery

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: metformin<br> | Drug: Metformin<br>* prior to CAGB surgery 3 day treatment with metformin 500 mg three times a day<br>* Other names: Glucophage;|
| Placebo Comparator: placebo<br> | Drug: Placebo<br>* prior to CABG surgery 3 day treatment with placebo capsules three times a day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hs-Troponin-I | high sensitive cardiac troponin-I | within 24 hours after CABG | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Post operative occurrence of arrhythmias |  | within 24 hours after CABG | 
| Duration of inotropic support |  | within two days after CABG | 
| Time to detubation |  | within two days after CABG | 
| Post-ischemic recovery of contractile function of atrial trabeculae |  | until 4 hours after harvesting | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ischemia reperfusion injury, CABG, metformin, Hs-troponin-I