To study whether pretreatment with metformin can reduce myocardial injury during CABG surgery in patients without diabetes mellitus.
ID
Source
Brief title
Condition
- Coronary artery disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
High-sensitive troponin-I levels measured before and 6,12 and 24 hours after
CABG.
Secondary outcome
Secondary endpoints will include the post-operative occurrence of arrhythmias,
the need for inotropic support, time to detubation, and time to discharge from
the intensive care unit. Moreover, renal injury and function will be secondary
endpoints of the study. Renal ischemia-reperfusion will be assessed by
measuring urinary excretion of the markers of tubular damage Kidney Injury
Molecule (KIM)-1 and neutrophil gelatinase-associated lipocalin (NGAL), and
renal function will be assessed by plasma and urine concentrations of
creatinine. Finally, the right auricle will be harvested during surgery to
determine whether metformin augments recovery of contractile function of
isolated atrial trabeculae after ex vivo simulated ischemia-reperfusion (vide
infra) and to determine the effect of metformin on the expression and
activation of protein kinases involved in ischemia-reperfusion injury (Western
blotting).
Background summary
In patients with a myocardial infarction, occlusion of a coronary artery
induces myocardial ischemia and cell death. 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 myocardial tissue is exposed to ischemia and reperfusion,
which will induce cell death. Indeed, postoperatively, the plasma concentration
of troponin I 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. Therefore, we
hypothesize that pretreatment with metformin can reduce myocardial injury in
patients undergoing elective CABG surgery.
Study objective
To study whether pretreatment with metformin can reduce myocardial injury
during CABG surgery in patients without diabetes mellitus.
Study design
Randomised, double-blinded, placebo-controlled clinical trial
Intervention
Pretreatment with metformin (500 mg three times a day for at least 3 days - max
7 days - ) or placebo until the day of surgery
Study burden and risks
This study will be executed at the Radboud University Nijmegen Medical
Centre,Groningen University Medical Centre and Maastricht University Medical
Centre, under close medical supervision. Treatment metformin or placebo is not
expected to harm the participants. We expect patients receiving metformin will
be suffer less myocardial injury after CABG. In some patients, metformin
treatment can give mild gastro-intestinal side effects, such as nausae,
bloating, and diarrhea. Lactic acidosis is an extremely rare side-effect with
an incidence of 1-5 per 100.000 patients, which can occur during metformin
accumulation during longterm treatment in the setting or renal insufficiency.
By excluding patients with renal insufficiency and due to the short-term
treatment with metformin, the risk of a lactic acidosis is even further
reduced.
Geert Grooteplein 21
6525 EZ Nijmegen
NL
Geert Grooteplein 21
6525 EZ Nijmegen
NL
Listed location countries
Age
Inclusion criteria
- Acceptation for CABG
- Informed consent
- Age >= 18 years
Exclusion criteria
- Diabetes mellitus
- Renal dysfunction (MDRD < 60 ml/min)
- Elevated liverenzymes (ALAT > 3 times upper limit of reference range)
- Treatment with dipyridamole or xanthine derivatives
- Recent myocardial infarction (<2 weeks before inclusion)
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2011-000099-33-NL |
| CCMO | NL35358.091.11 |