Metformin to Reduce Heart Failure After Myocardial Infarction (GIPS-III)
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.
ST Elevation Myocardial Infarction (STEMI)
Coronary Artery Disease
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||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.|
- Improvement in left ventricular ejection fraction [ Time Frame: 4 months ] [ Designated as safety issue: No ]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.
- the incidence of a cardiovascular event [ Time Frame: 4 months and longterm follow-up ] [ Designated as safety issue: Yes ]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 [ Time Frame: 4 months and longterm follow-up ] [ Designated as safety issue: Yes ]markers of heart failure: neurohormones (e.g. NT-proBNP), renal function (e.g. MDRD); glycometabolic state: e.g. HbA1c.
- Myocardial infarct size and transmural extent of infarction as measured with cardiac magnetic resonance imaging [ Time Frame: 4 months after hospitalization ] [ Designated as safety issue: No ]myocardial infarct size and transmural extent of infarction will be measured using Late Gadolinium Enhancement cardiac magnetic imaging
- diastolic function [ Time Frame: 4 months ] [ Designated as safety issue: No ]echocardiographic analysis of diastolic function
- glycometabolic state [ Time Frame: 4 months and long-term follow-up ] [ Designated as safety issue: No ]measured by oral glucose tolerance testing and Glycated Hemoglobin according to current criteria
- Cardiac MRI after 4 months, per protocol analysis [ Time Frame: 4 months ] [ Designated as safety issue: No ]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
|Study Start Date:||January 2011|
|Estimated Study Completion Date:||May 2015|
|Primary Completion Date:||October 2013 (Final data collection date for primary outcome measure)|
metformin 500mg twice daily during 4 months
Metformin 500mg twice daily during 4 months
Other Name: Glucophage
Placebo Comparator: Placebo
Placebo twice daily during 4 months
Placebo twice daily during 4 months
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01217307
|University Medical Center Groningen|
|Groningen, Netherlands, 9700RB|
|Principal Investigator:||Iwan CC van der Horst, MD, PhD||Thorax Centre, University Medical Centre Groningen|