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Metformin to Reduce Heart Failure After Myocardial Infarction (GIPS-III)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
ZonMw: The Netherlands Organisation for Health Research and Development
Information provided by (Responsible Party):
Chris Lexis, University Medical Centre Groningen
ClinicalTrials.gov Identifier:
NCT01217307
First received: October 7, 2010
Last updated: October 16, 2013
Last verified: October 2013

October 7, 2010
October 16, 2013
January 2011
October 2013   (final data collection date for primary outcome measure)
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.
Improvement in left ventricular ejection fraction [ Time Frame: 4 months ] [ Designated as safety issue: No ]
Paired cardiac magnetic resonance imaging during index hospitalization and 4 months after randomization will be performed to assess left ventricular function. It is hypothesized that metformin therapy will result in a higher ejection fraction after 4 months.
Complete list of historical versions of study NCT01217307 on ClinicalTrials.gov Archive Site
  • 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
  • the incidence of a cardiovascular event [ Time Frame: 4 months and longterm follow-up ] [ Designated as safety issue: No ]
    Cardiovascular event: mortality (cardiovascular or other), re-infarction, re-coronary intervention, stroke, hospitalization for heart failure.
  • 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: during hospitalization and 4 months ] [ Designated as safety issue: No ]
    myocardial infarct size and transmural extent of infarction will be measured using Late Gadolinium Enhancement cardiac magnetic imaging
Not Provided
Not Provided
 
Metformin to Reduce Heart Failure After Myocardial Infarction
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.

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.

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.

Interventional
Phase 2
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
  • ST Elevation Myocardial Infarction (STEMI)
  • Coronary Artery Disease
  • Heart Failure
  • Diabetes
  • Drug: Metformin
    Metformin 500mg twice daily during 4 months
    Other Name: Glucophage
  • Drug: Placebo
    Placebo twice daily during 4 months
  • Experimental: Metformin
    metformin 500mg twice daily during 4 months
    Intervention: Drug: Metformin
  • Placebo Comparator: Placebo
    Placebo twice daily during 4 months
    Intervention: Drug: Placebo

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
380
May 2015
October 2013   (final data collection date for primary outcome measure)

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.
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Netherlands
 
NCT01217307
GIPS-III 2010B257
Yes
Chris Lexis, University Medical Centre Groningen
University Medical Centre Groningen
ZonMw: The Netherlands Organisation for Health Research and Development
Principal Investigator: Iwan CC van der Horst, MD, PhD Thorax Centre, University Medical Centre Groningen
University Medical Centre Groningen
October 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP