Metformin to Reduce Heart Failure After Myocardial Infarction

NCT ID: NCT01217307

Last Updated: 2018-01-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 380 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-01-31
• Study Completion Date: 2015-10-31

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.

Conditions

ST Elevation Myocardial Infarction (STEMI); Coronary Artery Disease; Heart Failure; Diabetes

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Metformin

metformin 500mg twice daily during 4 months

Group Type: EXPERIMENTAL

Metformin

Intervention Type: DRUG

Metformin 500mg twice daily during 4 months

Placebo

Placebo twice daily during 4 months

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo twice daily during 4 months

Interventions

Metformin

Metformin 500mg twice daily during 4 months

Intervention Type: DRUG

Placebo

Placebo twice daily during 4 months

Intervention Type: DRUG

Other Intervention Names

Glucophage

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

ZonMw: The Netherlands Organisation for Health Research and Development

OTHER

Sponsor Role: collaborator

University Medical Center Groningen

OTHER

Sponsor Role: lead

Responsible Party

Chris Lexis

Drs.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Iwan CC van der Horst, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Thorax Centre, University Medical Centre Groningen

Locations

University Medical Center Groningen

Groningen, , Netherlands

Countries

Netherlands

References

Al Ali L, Groot HE, Assa S, Lipsic E, Hummel YM, van Veldhuisen DJ, Voors AA, van der Horst ICC, Lam CS, van der Harst P. Predictors of adverse diastolic remodeling in non-diabetic patients presenting with ST-elevation myocardial infarction. BMC Cardiovasc Disord. 2023 Jan 23;23(1):44. doi: 10.1186/s12872-023-03064-7.

Reference Type: DERIVED

PMID: 36690932 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 34593124 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 28755285 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 28100626 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 26808474 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 26688733 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 24687169 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 22968678 (View on PubMed)

Other Identifiers

GIPS-III 2010B257

Identifier Type: -

Identifier Source: org_study_id