Clinical trial NCT01217307: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: ST Elevation Myocardial Infarction (STEMI)
Coronary Artery Disease
Heart Failure
Diabetes
Keywords: Metformin
ST elevation myocardial infarction (STEMI)
Coronary artery disease
Heart failure
Diabetes
Lead sponsor: University Medical Center Groningen
Sponsor class: OTHER
Collaborators: name: ZonMw: The Netherlands Organisation for Health Research and Development
First posted: 2010-10-08
Enrollment: 380
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Improvement in Left Ventricular Ejection Fraction
timeFrame: 4 months
Secondary outcomes:
measure: the Incidence of a Cardiovascular Event
timeFrame: 4 months and longterm follow-up
measure: Markers of Heart Failure and Glycometabolic State
timeFrame: 4 months and longterm follow-up
measure: Myocardial Infarct Size and Transmural Extent of Infarction as Measured With Cardiac Magnetic Resonance Imaging
timeFrame: 4 months after hospitalization
measure: Diastolic Function
timeFrame: 4 months
measure: Glycometabolic State
timeFrame: 4 months and long-term follow-up
measure: Cardiac MRI After 4 Months, Per Protocol Analysis
timeFrame: 4 months
Other outcomes:
Locations:
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
Study officials:
affiliation: Thorax Centre, University Medical Centre Groningen
name: Iwan CC van der Horst, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: de Koning MLY, Westenbrink BD, Assa S, Garcia E, Connelly MA, van Veldhuisen DJ, Dullaart RPF, Lipsic E, van der Harst P. Association of Circulating Ketone Bodies With Functional Outcomes After ST-Segment Elevation Myocardial Infarction. J Am Coll Cardiol. 2021 Oct 5;78(14):1421-1432. doi: 10.1016/j.jacc.2021.07.054.
citation: Hartman MHT, Prins JKB, Schurer RAJ, Lipsic E, Lexis CPH, van der Horst-Schrivers ANA, van Veldhuisen DJ, van der Horst ICC, van der Harst P. Two-year follow-up of 4 months metformin treatment vs. placebo in ST-elevation myocardial infarction: data from the GIPS-III RCT. Clin Res Cardiol. 2017 Dec;106(12):939-946. doi: 10.1007/s00392-017-1140-z. Epub 2017 Jul 28.
citation: Eppinga RN, Kofink D, Dullaart RP, Dalmeijer GW, Lipsic E, van Veldhuisen DJ, van der Horst IC, Asselbergs FW, van der Harst P. Effect of Metformin on Metabolites and Relation With Myocardial Infarct Size and Left Ventricular Ejection Fraction After Myocardial Infarction. Circ Cardiovasc Genet. 2017 Feb;10(1):e001564. doi: 10.1161/CIRCGENETICS.116.001564.
citation: Eppinga RN, Hartman MH, van Veldhuisen DJ, Lexis CP, Connelly MA, Lipsic E, van der Horst IC, van der Harst P, Dullaart RP. Effect of Metformin Treatment on Lipoprotein Subfractions in Non-Diabetic Patients with Acute Myocardial Infarction: A Glycometabolic Intervention as Adjunct to Primary Coronary Intervention in ST Elevation Myocardial Infarction (GIPS-III) Trial. PLoS One. 2016 Jan 25;11(1):e0145719. doi: 10.1371/journal.pone.0145719. eCollection 2016.
citation: Lexis CP, van der Horst-Schrivers AN, Lipsic E, Valente MA, Muller Kobold AC, de Boer RA, van Veldhuisen DJ, van der Harst P, van der Horst IC. The effect of metformin on cardiovascular risk profile in patients without diabetes presenting with acute myocardial infarction: data from the Glycometabolic Intervention as adjunct to Primary Coronary Intervention in ST Elevation Myocardial Infarction (GIPS-III) trial. BMJ Open Diabetes Res Care. 2015 Dec 11;3(1):e000090. doi: 10.1136/bmjdrc-2015-000090. eCollection 2015.
citation: Lexis CP, van der Horst IC, Lipsic E, Wieringa WG, de Boer RA, van den Heuvel AF, van der Werf HW, Schurer RA, Pundziute G, Tan ES, Nieuwland W, Willemsen HM, Dorhout B, Molmans BH, van der Horst-Schrivers AN, Wolffenbuttel BH, ter Horst GJ, van Rossum AC, Tijssen JG, Hillege HL, de Smet BJ, van der Harst P, van Veldhuisen DJ; GIPS-III Investigators. Effect of metformin on left ventricular function after acute myocardial infarction in patients without diabetes: the GIPS-III randomized clinical trial. JAMA. 2014 Apr 16;311(15):1526-35. doi: 10.1001/jama.2014.3315.
citation: Lexis CP, van der Horst IC, Lipsic E, van der Harst P, van der Horst-Schrivers AN, Wolffenbuttel BH, de Boer RA, van Rossum AC, van Veldhuisen DJ, de Smet BJ; GIPS-III Investigators. Metformin in non-diabetic patients presenting with ST elevation myocardial infarction: rationale and design of the glycometabolic intervention as adjunct to primary percutaneous intervention in ST elevation myocardial infarction (GIPS)-III trial. Cardiovasc Drugs Ther. 2012 Oct;26(5):417-26. doi: 10.1007/s10557-012-6413-1.