Metformin to Reduce Heart Failure After Myocardial Infarction

Coronary Artery Disease Clinical Trial

— GIPS-III  

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01217307
• Other study ID #: GIPS-III 2010B257
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: October 7, 2010
• Last updated: July 31, 2017
• Start date: January 2011
• Est. completion date: October 2015

Study information

• Verified date: July 2017
• Source: University Medical Center Groningen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 380
• Est. completion date: October 2015
• Est. primary completion date: October 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• Diabetes
• Heart Failure
• Infarction
• Myocardial Infarction
• Myocardial Ischemia
• ST Elevation Myocardial Infarction
• ST Elevation Myocardial Infarction (STEMI)

Intervention

Drug:
• Metformin
Metformin 500mg twice daily during 4 months
• Placebo
Placebo twice daily during 4 months

Locations

Country	Name	City	State
Netherlands	University Medical Center Groningen	Groningen

Sponsors (2)

Lead Sponsor	Collaborator
University Medical Center Groningen	ZonMw: The Netherlands Organisation for Health Research and Development

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	Diastolic Function	echocardiographic analysis of diastolic function	4 months
Secondary	Glycometabolic State	measured by oral glucose tolerance testing and Glycated Hemoglobin according to current criteria	4 months and long-term follow-up
Secondary	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