Metformin to Reduce Heart Failure After Myocardial Infarction

Study Overview
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Brief Summary
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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
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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.

Official Title
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Metabolic Modulation With Metformin to Reduce Heart Failure After Acute Myocardial Infarction: Glycometabolic Intervention as Adjunct to Primary Coronary Intervention in ST Elevation Myocardial Infarction (GIPS-III): a Randomized Controlled Trial.

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

Intervention / Treatment
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* Drug: Metformin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Metformin<br>metformin 500mg twice daily during 4 months | Drug: Metformin<br>* Metformin 500mg twice daily during 4 months<br>* Other names: Glucophage;|
| Placebo Comparator: Placebo<br>Placebo twice daily during 4 months | Drug: Placebo<br>* Placebo twice daily during 4 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement in Left Ventricular Ejection Fraction | 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. | 4 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the Incidence of a Cardiovascular Event | 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. | 4 months and longterm follow-up | 
| Markers of Heart Failure and Glycometabolic State | markers of heart failure: neurohormones (e.g. NT-proBNP), renal function (e.g. MDRD); glycometabolic state: e.g. HbA1c. | 4 months and longterm follow-up | 
| Myocardial Infarct Size and Transmural Extent of Infarction as Measured With Cardiac Magnetic Resonance Imaging | myocardial infarct size and transmural extent of infarction will be measured using Late Gadolinium Enhancement cardiac magnetic imaging | 4 months after hospitalization | 
| Diastolic Function | echocardiographic analysis of diastolic function | 4 months | 
| Glycometabolic State | measured by oral glucose tolerance testing and Glycated Hemoglobin according to current criteria | 4 months and long-term follow-up | 
| Cardiac MRI After 4 Months, Per Protocol Analysis | 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 | 4 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Metformin, ST elevation myocardial infarction (STEMI), Coronary artery disease, Heart failure, Diabetes