Metformin to Reduce Heart Failure After Myocardial Infarction

Phase 2

Completed

Conditions: ST Elevation Myocardial Infarction (STEMI)
Coronary Artery Disease
Diabetes
Heart Failure

Interventions: Drug: Placebo
Drug: Metformin

Registration Number: NCT01217307

Lead Sponsor: University Medical Center Groningen

Brief Summary: The investigators will evaluate the effect of metformin therapy during 4 months in non-diabetic patients following ST-elevation myocardial infarction on left ventricular ejection fraction as measured with cardiac magnetic resonance imaging, compared to placebo.

Detailed Description: In this trial, the investigators will evaluate the effect of metformin therapy following ST-elevation myocardial infarction (STEMI) in a total of 380 non-diabetic patients. This trial is a randomized, double blind, controlled trial. The intervention, which consist of metformin 500mg twice daily or placebo twice daily, will commence within three hours after the percutaneous coronary intervention, and will be continued for 4 months. The primary endpoint is the difference between the two intervention groups (metformin vs placebo) in left ventricular ejection fraction, as measured with magnetic resonance imaging after 4 months. The investigators hypothesize that metformin therapy results in a significantly higher ejection fraction in this population.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 380

Inclusion Criteria

The diagnosis acute MI defined by chest pain suggestive for myocardial ischemia for at least 30 minutes, the time from onset of the symptoms less than 12 hours before hospital admission, and an ECG recording with ST- segment elevation of more than 0.1 mV in 2 or more leads.
Successful primary PCI (post-procedural TIMI 2/3);
At least one stent sized ≥ 3.0 mm;
Eligible for 3T CMR imaging;
Verbal followed by written informed consent.

Exclusion Criteria

rescue PCI after thrombolytic therapy;
need for emergency coronary artery bypass grafting;
creatinin >177 μmol/L measured pre-PCI;
Younger than 18 years;
Mechanical ventilation;
Diabetes;
Prior myocardial infarction;
Contra-indication to metformin (see safety);
The existence of a life-threatening disease with a life-expectancy of less than 6 months.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Placebo twice daily during 4 months
Metformin	Metformin	metformin 500mg twice daily during 4 months

Primary Outcome Measures

Name	Time	Method
Improvement in Left Ventricular Ejection Fraction	4 months	The primary efficacy parameter of the GIPS-III trial is LVEF measured by cardiac MRI 4 months after randomization, based on an intention-to-treat analysis. It is hypothesized that metformin therapy will result in a higher ejection fraction after 4 months.

Secondary Outcome Measures

Name	Time	Method
Glycometabolic State	4 months and long-term follow-up	measured by oral glucose tolerance testing and Glycated Hemoglobin according to current criteria
Diastolic Function	4 months	echocardiographic analysis of diastolic function
Myocardial Infarct Size and Transmural Extent of Infarction as Measured With Cardiac Magnetic Resonance Imaging	4 months after hospitalization	myocardial infarct size and transmural extent of infarction will be measured using Late Gadolinium Enhancement cardiac magnetic imaging
Cardiac MRI After 4 Months, Per Protocol Analysis	4 months	A per-protocol analysis, excluding patients diagnosed with new onset diabetes and treated with oral antihyperglycemic agents or insulin prior to cardiac MRI, will be performed as a secondary efficacy parameter
the Incidence of a Cardiovascular Event	4 months and longterm follow-up	Cardiovascular events include major cardiac adverse events (MACE; death, recurrent MI, target lesion revascularization), stroke, non-elective hospitalizations for chest pain or heart failure, all recurrent coronary interventions, and internal cardiac defibrillator implantations. Mortality will be divided into cardiac and non-cardiac. Cardiac death will be divided into three categories: heart failure, sudden death and other. A cardiologist will confirm deaths from cardiovascular causes by examining medical records obtained from hospitals and attending physicians or from attending general practitioner if the patient died at home.
Markers of Heart Failure and Glycometabolic State	4 months and longterm follow-up	markers of heart failure: neurohormones (e.g. NT-proBNP), renal function (e.g. MDRD); glycometabolic state: e.g. HbA1c.