Try our beta test site
IMPORTANT: Listing of a study on this site does not reflect endorsement by the National Institutes of Health. Talk with a trusted healthcare professional before volunteering for a study. Read more...

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

The recruitment status of this study is unknown. The completion date has passed and the status has not been verified in more than two years.
Verified October 2013 by Chris Lexis, University Medical Centre Groningen.
Recruitment status was:  Active, not recruiting
ZonMw: The Netherlands Organisation for Health Research and Development
Information provided by (Responsible Party):
Chris Lexis, University Medical Centre Groningen Identifier:
First received: October 7, 2010
Last updated: October 16, 2013
Last verified: October 2013
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.

Condition Intervention Phase
ST Elevation Myocardial Infarction (STEMI)
Coronary Artery Disease
Heart Failure
Drug: Metformin
Drug: Placebo
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Participant, Care Provider, 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.

Resource links provided by NLM:

Further study details as provided by Chris Lexis, University Medical Centre Groningen:

Primary Outcome Measures:
  • Improvement in left ventricular ejection fraction [ Time Frame: 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:
  • the incidence of a cardiovascular event [ Time Frame: 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 [ Time Frame: 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.

  • Myocardial infarct size and transmural extent of infarction as measured with cardiac magnetic resonance imaging [ Time Frame: 4 months after hospitalization ]
    myocardial infarct size and transmural extent of infarction will be measured using Late Gadolinium Enhancement cardiac magnetic imaging

  • diastolic function [ Time Frame: 4 months ]
    echocardiographic analysis of diastolic function

  • glycometabolic state [ Time Frame: 4 months and long-term follow-up ]
    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 ]
    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

Estimated Enrollment: 380
Study Start Date: January 2011
Estimated Study Completion Date: May 2015
Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Metformin
metformin 500mg twice daily during 4 months
Drug: Metformin
Metformin 500mg twice daily during 4 months
Other Name: Glucophage
Placebo Comparator: Placebo
Placebo twice daily during 4 months
Drug: Placebo
Placebo twice daily during 4 months

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.

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01217307

University Medical Center Groningen
Groningen, Netherlands, 9700RB
Sponsors and Collaborators
University Medical Center 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
  More Information

Publications automatically indexed to this study by Identifier (NCT Number):

Responsible Party: Chris Lexis, Drs., University Medical Centre Groningen Identifier: NCT01217307     History of Changes
Other Study ID Numbers: GIPS-III 2010B257
Study First Received: October 7, 2010
Last Updated: October 16, 2013

Keywords provided by Chris Lexis, University Medical Centre Groningen:
ST elevation myocardial infarction (STEMI)
Coronary artery disease
Heart failure

Additional relevant MeSH terms:
Heart Failure
Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Myocardial Infarction
Heart Diseases
Cardiovascular Diseases
Pathologic Processes
Arterial Occlusive Diseases
Vascular Diseases
Hypoglycemic Agents
Physiological Effects of Drugs processed this record on May 25, 2017