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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
  Purpose

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
Diabetes
Drug: Metformin
Drug: Placebo
Phase 2
Phase 3

Study Type: Interventional
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.

Resource links provided by NLM:


Further study details as provided by University Medical Centre Groningen:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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


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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 ClinicalTrials.gov identifier: NCT01217307

Locations
Netherlands
University Medical Center Groningen
Groningen, Netherlands, 9700RB
Sponsors and Collaborators
University Medical Centre Groningen
ZonMw: The Netherlands Organisation for Health Research and Development
Investigators
Principal Investigator: Iwan CC van der Horst, MD, PhD Thorax Centre, University Medical Centre Groningen
  More Information

No publications provided by University Medical Centre Groningen

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Chris Lexis, Drs., University Medical Centre Groningen
ClinicalTrials.gov Identifier: NCT01217307     History of Changes
Other Study ID Numbers: GIPS-III 2010B257
Study First Received: October 7, 2010
Last Updated: October 16, 2013
Health Authority: Netherlands: Medical Ethics Review Committee (METC)
Netherlands: Central Committee on Research inv. Human Subjects (CCMO)

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

Additional relevant MeSH terms:
Coronary Artery Disease
Coronary Disease
Heart Failure
Infarction
Myocardial Infarction
Myocardial Ischemia
Arterial Occlusive Diseases
Arteriosclerosis
Cardiovascular Diseases
Heart Diseases
Ischemia
Necrosis
Pathologic Processes
Vascular Diseases
Metformin
Hypoglycemic Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on November 25, 2014