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

Overview[ - collapse ][ - ]

Purpose 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
ConditionCardiovascular Disease
Ischemic Heart Disease
InterventionDrug: Metformin
Drug: Placebo
PhasePhase 4
SponsorRadboud University
Responsible PartyRadboud University
ClinicalTrials.gov IdentifierNCT01438723
First ReceivedSeptember 21, 2011
Last UpdatedApril 26, 2013
Last verifiedNovember 2011

Tracking Information[ + expand ][ + ]

First Received DateSeptember 21, 2011
Last Updated DateApril 26, 2013
Start DateNovember 2011
Estimated Primary Completion DateDecember 2013
Current Primary Outcome MeasuresHs-Troponin-I [Time Frame: within 72 hours after CABG] [Designated as safety issue: No]high sensitive cardiac troponin-I
Current Secondary Outcome Measures
  • Post operative occurrence of arrhythmias [Time Frame: within 24 hours after CABG] [Designated as safety issue: No]
  • Duration of inotropic support [Time Frame: within three days after CABG] [Designated as safety issue: No]
  • Time to detubation [Time Frame: within three days after CABG] [Designated as safety issue: No]
  • Post-ischemic recovery of contractile function of atrial trabeculae [Time Frame: until 4 hours after harvesting] [Designated as safety issue: No]
  • renal ischemia-reperfusion injury [Time Frame: within three days after CABG] [Designated as safety issue: No]

Descriptive Information[ + expand ][ + ]

Brief TitleThe Metformin in Coronary Artery Bypass Graft (CABG) (MetCAB) Trial
Official TitleThe Metformin in CABG (MetCAB) Trial
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
Detailed DescriptionNot Provided
Study TypeInterventional
Study PhasePhase 4
Study DesignAllocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention
Condition
  • Cardiovascular Disease
  • Ischemic Heart Disease
InterventionDrug: Metformin
prior to CAGB surgery 3 day treatment with metformin 500 mg three times a day
Other Names:
GlucophageDrug: Placebo
prior to CABG surgery 3 day treatment with placebo capsules three times a day
Study Arm (s)
  • Experimental: metformin
  • Placebo Comparator: placebo

Recruitment Information[ + expand ][ + ]

Recruitment StatusRecruiting
Estimated Enrollment110
Estimated Completion DateDecember 2013
Estimated Primary Completion DateJuly 2013
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
GenderBoth
Ages18 Years
Accepts Healthy VolunteersNo
ContactsContact: S El Messaoudi, MD MSc
+31 24 3616723
S.ElMessaoudi@cardio.umcn.nl
Location CountriesNetherlands

Administrative Information[ + expand ][ + ]

NCT Number NCT01438723
Other Study ID NumbersMetCAB
Has Data Monitoring CommitteeYes
Information Provided ByRadboud University
Study SponsorRadboud University
CollaboratorsNot Provided
Investigators Not Provided
Verification DateNovember 2011

Locations[ + expand ][ + ]

RUNMC
Nijmegen, Gelderland, Netherlands
Contact: S El Messaoudi, MD MSc | +31 24 3616723 | S.ElMessaoudi@cardio.umcn.nl
Principal Investigator: G Rongen, MD PhD
Recruiting