Metformin to Reduce Heart Failure After Myocardial Infarction | RxWiki

Metformin to Reduce Heart Failure After Myocardial Infarction

Overview[ - collapse ][ - ]

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	ST Elevation Myocardial Infarction (STEMI) Coronary Artery Disease Heart Failure Diabetes
Intervention	Drug: Metformin Drug: Placebo
Phase	Phase 2/Phase 3
Sponsor	University Medical Centre Groningen
Responsible Party	University Medical Centre Groningen
ClinicalTrials.gov Identifier	NCT01217307
First Received	October 7, 2010
Last Updated	October 16, 2013
Last verified	October 2013

Tracking Information[ + expand ][ + ]

First Received Date	October 7, 2010
Last Updated Date	October 16, 2013
Start Date	January 2011
Estimated Primary Completion Date	May 2015
Current 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.
Current 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

Descriptive Information[ + expand ][ + ]

Brief Title	Metformin to Reduce Heart Failure After Myocardial Infarction
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.
Brief 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.
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.
Study Type	Interventional
Study Phase	Phase 2/Phase 3
Study Design	Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Condition	ST Elevation Myocardial Infarction (STEMI) Coronary Artery Disease Heart Failure Diabetes
Intervention	Drug: Metformin Metformin 500mg twice daily during 4 months Other Names: GlucophageDrug: Placebo Placebo twice daily during 4 months
Study Arm (s)	Experimental: Metformin metformin 500mg twice daily during 4 months Placebo Comparator: Placebo Placebo twice daily during 4 months

Recruitment Information[ + expand ][ + ]

Recruitment Status	Active, not recruiting
Estimated Enrollment	380
Estimated Completion Date	May 2015
Estimated Primary Completion Date	October 2013
Eligibility 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.
Gender	Both
Ages	18 Years
Accepts Healthy Volunteers	No
Contacts	Not Provided
Location Countries	Netherlands

Administrative Information[ + expand ][ + ]

NCT Number	NCT01217307
Other Study ID Numbers	GIPS-III 2010B257
Has Data Monitoring Committee	Yes
Information Provided By	University Medical Centre Groningen
Study Sponsor	University Medical Centre Groningen
Collaborators	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
Verification Date	October 2013

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