Metformin to Reduce Heart Failure After Myocardial Infarction

NCT01217307 | Completed Phase 2 Results DMC

• 1 other identifier: GIPS-III 2010B257
• Study Type: interventional
• Target: 380
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (1)

• Improvement in Left Ventricular Ejection Fraction

  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.

  4 months

Secondary Outcomes (6)

• the Incidence of a Cardiovascular Event

  4 months and longterm follow-up

• Markers of Heart Failure and Glycometabolic State

  4 months and longterm follow-up

• Myocardial Infarct Size and Transmural Extent of Infarction as Measured With Cardiac Magnetic Resonance Imaging

  4 months after hospitalization

• Diastolic Function

  4 months

• Glycometabolic State

  4 months and long-term follow-up

Study Arms (2)

Metformin

EXPERIMENTAL

metformin 500mg twice daily during 4 months

Drug: Metformin

Placebo

PLACEBO COMPARATOR

Placebo twice daily during 4 months

Drug: Placebo

Interventions

Metformin DRUG

Metformin 500mg twice daily during 4 months

Also known as: Glucophage

Metformin

Placebo DRUG

Placebo twice daily during 4 months

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University Medical Center Groningen: lead
• ZonMw: The Netherlands Organisation for Health Research and Development: collaborator

Study Sites (1)

University Medical Center Groningen

Groningen, 9700RB, Netherlands

Location

Related Publications (8)

• 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.

  PMID: 36690932 DERIVED

• 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.

  PMID: 34593124 DERIVED

• 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.

  PMID: 28755285 DERIVED

• 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.

  PMID: 28100626 DERIVED

• 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.

  PMID: 26808474 DERIVED

• 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.

  PMID: 26688733 DERIVED

• 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.

  PMID: 24687169 DERIVED

• 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.

  PMID: 22968678 DERIVED

MeSH Terms

Conditions

ST Elevation Myocardial Infarction; Coronary Artery Disease; Heart Failure; Diabetes Mellitus

Interventions

Metformin

Condition Hierarchy (Ancestors)

Myocardial Infarction; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis; Coronary Disease; Arteriosclerosis; Arterial Occlusive Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Results Point of Contact

• Title: Dr. I.C.C. van der Horst
• Organization: University Medical Center Groningen

i.c.c.van.der.horst@umcg.nl

Study Officials

• Iwan CC van der Horst, MD, PhD

  Thorax Centre, University Medical Centre Groningen

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Drs.

Study Record Dates

• First Submitted: October 7, 2010
• First Posted: October 8, 2010
• Study Start: January 1, 2011
• Primary Completion: October 1, 2013
• Study Completion: October 1, 2015
• Last Updated: January 30, 2018
• Results First Posted: January 30, 2018

Record last verified: 2017-07

Locations

NL (1)