NCT01438723

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

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
100

participants targeted

Target at P50-P75 for phase_4

Timeline
Completed

Started Nov 2011

Typical duration for phase_4

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

September 21, 2011

Completed
1 day until next milestone

First Posted

Study publicly available on registry

September 22, 2011

Completed
1 month until next milestone

Study Start

First participant enrolled

November 1, 2011

Completed
2.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 1, 2014

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

July 1, 2014

Completed
Last Updated

July 29, 2014

Status Verified

November 1, 2011

Enrollment Period

2.7 years

First QC Date

September 21, 2011

Last Update Submit

July 28, 2014

Conditions

Cardiovascular DiseaseIschemic Heart Disease

Keywords

ischemia reperfusion injuryCABGmetforminHs-troponin-I

Outcome Measures

Primary Outcomes (1)

  • Hs-Troponin-I

    high sensitive cardiac troponin-I

    within 24 hours after CABG

Secondary Outcomes (4)

  • 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

Study Arms (2)

metformin

EXPERIMENTAL
Drug: Metformin

placebo

PLACEBO COMPARATOR
Drug: Placebo

Interventions

MetforminDRUG

prior to CAGB surgery 3 day treatment with metformin 500 mg three times a day

Also known as: Glucophage
metformin
PlaceboDRUG

prior to CABG surgery 3 day treatment with placebo capsules three times a day

placebo

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Acceptation for CABG with or without concomitant valve surgery
  • Informed consent
  • Age ≥ 18 years

You may not qualify if:

  • 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
  • Off-pump surgery

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

RUNMC

Nijmegen, Gelderland, Netherlands

Location

Related Publications (2)

  • 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.

    PMID: 26179504DERIVED

  • 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.

    PMID: 24622709DERIVED

MeSH Terms

Conditions

Cardiovascular DiseasesMyocardial IschemiaReperfusion Injury

Interventions

Metformin

Condition Hierarchy (Ancestors)

Heart DiseasesVascular DiseasesPostoperative ComplicationsPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

BiguanidesGuanidinesAmidinesOrganic Chemicals

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 21, 2011

First Posted

September 22, 2011

Study Start

November 1, 2011

Primary Completion

July 1, 2014

Study Completion

July 1, 2014

Last Updated

July 29, 2014

Record last verified: 2011-11

Locations

NL(1)