Clinical trial NCT01438723: The Metformin in Coronary Artery Bypass Graft (CABG) (MetCAB) Trial
Official title: The Metformin in CABG (MetCAB) Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Cardiovascular Disease
Ischemic Heart Disease
Keywords: ischemia reperfusion injury
CABG
metformin
Hs-troponin-I
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
First posted: 2011-09-22
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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


Eligibility criteria: 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

Primary outcomes:
measure: Hs-Troponin-I
timeFrame: within 24 hours after CABG
Secondary outcomes:
measure: Post operative occurrence of arrhythmias
timeFrame: within 24 hours after CABG
measure: Duration of inotropic support
timeFrame: within two days after CABG
measure: Time to detubation
timeFrame: within two days after CABG
measure: Post-ischemic recovery of contractile function of atrial trabeculae
timeFrame: until 4 hours after harvesting
Other outcomes:
Locations:
city: Nijmegen
country: Netherlands
facility: RUNMC
state: Gelderland
Study officials:
References:
citation: El Messaoudi S, Nederlof R, Zuurbier CJ, van Swieten HA, Pickkers P, Noyez L, Dieker HJ, Coenen MJ, Donders AR, Vos A, Rongen GA, Riksen NP. Effect of metformin pretreatment on myocardial injury during coronary artery bypass surgery in patients without diabetes (MetCAB): a double-blind, randomised controlled trial. Lancet Diabetes Endocrinol. 2015 Aug;3(8):615-23. doi: 10.1016/S2213-8587(15)00121-7. Epub 2015 Jul 12.
citation: Riksen NP, el Messaoudi S, Rongen GA. It takes more than one CAMERA to study cardiovascular protection by metformin. Lancet Diabetes Endocrinol. 2014 Feb;2(2):105-6. doi: 10.1016/S2213-8587(13)70207-9. Epub 2014 Feb 3. No abstract available.