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| Name | Class |
|---|---|
| ZonMw: The Netherlands Organisation for Health Research and Development | OTHER |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Metformin | Experimental | metformin 500mg twice daily during 4 months |
|
| Placebo | Placebo Comparator | Placebo twice daily during 4 months |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Metformin | Drug | Metformin 500mg twice daily during 4 months |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| the Incidence of a Cardiovascular Event | 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Iwan CC van der Horst, MD, PhD | Thorax Centre, University Medical Centre Groningen | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University Medical Center Groningen | Groningen | 9700RB | Netherlands |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36690932 | Derived | 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. | |
| 34593124 |
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| ID | Title | Description |
|---|---|---|
| FG000 | Metformin | metformin 500mg twice daily during 4 months Metformin: Metformin 500mg twice daily during 4 months |
| FG001 | Placebo | Placebo twice daily during 4 months Placebo: Placebo twice daily during 4 months |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Metformin | metformin 500mg twice daily during 4 months Metformin: Metformin 500mg twice daily during 4 months |
| BG001 | Placebo | Placebo twice daily during 4 months Placebo: Placebo twice daily during 4 months |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | patients undergoing primary percutaneous coronary intervention (PCI) for STEMI | Posted | Mean | 95% Confidence Interval | % of LVEF | 4 months |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Metformin | metformin 500mg twice daily during 4 months Metformin: Metformin 500mg twice daily during 4 months |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Reinfarction | Cardiac disorders | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Non-target lesion revascularization | Cardiac disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. I.C.C. van der Horst | University Medical Center Groningen | i.c.c.van.der.horst@umcg.nl |
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| ID | Term |
|---|---|
| D000072657 | ST Elevation Myocardial Infarction |
| D003324 | Coronary Artery Disease |
| D006333 | Heart Failure |
| D003920 | Diabetes Mellitus |
| ID | Term |
|---|---|
| D009203 | Myocardial Infarction |
| D017202 | Myocardial Ischemia |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
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| ID | Term |
|---|---|
| D008687 | Metformin |
| ID | Term |
|---|---|
| D001645 | Biguanides |
| D006146 | Guanidines |
| D000578 | Amidines |
| D009930 | Organic Chemicals |
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| Placebo | Drug | Placebo twice daily during 4 months |
|
| 4 months and longterm follow-up |
| Markers of Heart Failure and Glycometabolic State | markers of heart failure: neurohormones (e.g. NT-proBNP), renal function (e.g. MDRD); glycometabolic state: e.g. HbA1c. | 4 months and longterm follow-up |
| Myocardial Infarct Size and Transmural Extent of Infarction as Measured With Cardiac Magnetic Resonance Imaging | myocardial infarct size and transmural extent of infarction will be measured using Late Gadolinium Enhancement cardiac magnetic imaging | 4 months after hospitalization |
| Diastolic Function | echocardiographic analysis of diastolic function | 4 months |
| Glycometabolic State | measured by oral glucose tolerance testing and Glycated Hemoglobin according to current criteria | 4 months and long-term follow-up |
| Cardiac MRI After 4 Months, Per Protocol Analysis | 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 | 4 months |
| 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. |
| 28755285 | 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. |
| 28100626 | 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. |
| 26808474 | 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. |
| 26688733 | 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. |
| 24687169 | 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. |
| 22968678 | 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. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
|
|
| Secondary | the Incidence of a Cardiovascular Event | 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. | Not Posted | 4 months and longterm follow-up | Participants |
| Secondary | Markers of Heart Failure and Glycometabolic State | markers of heart failure: neurohormones (e.g. NT-proBNP), renal function (e.g. MDRD); glycometabolic state: e.g. HbA1c. | Not Posted | 4 months and longterm follow-up | Participants |
| Secondary | Myocardial Infarct Size and Transmural Extent of Infarction as Measured With Cardiac Magnetic Resonance Imaging | myocardial infarct size and transmural extent of infarction will be measured using Late Gadolinium Enhancement cardiac magnetic imaging | Not Posted | 4 months after hospitalization | Participants |
| Secondary | Diastolic Function | echocardiographic analysis of diastolic function | Not Posted | 4 months | Participants |
| Secondary | Glycometabolic State | measured by oral glucose tolerance testing and Glycated Hemoglobin according to current criteria | Not Posted | 4 months and long-term follow-up | Participants |
| Secondary | Cardiac MRI After 4 Months, Per Protocol Analysis | 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 | Not Posted | 4 months | Participants |
| 3 |
| 191 |
| 11 |
| 191 |
| 73 |
| 191 |
| EG001 | Placebo | Placebo twice daily during 4 months Placebo: Placebo twice daily during 4 months | 1 | 188 | 6 | 188 | 51 | 188 |
| Cardiovascular death | Cardiac disorders | Systematic Assessment |
|
| Target lesion revascularization | Cardiac disorders | Systematic Assessment |
|
| CABG | Cardiac disorders | Systematic Assessment |
|
| Hospitalization for chest pain | Cardiac disorders | Systematic Assessment |
|
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| D014652 |
| Vascular Diseases |
| D007238 | Infarction |
| D007511 | Ischemia |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D009336 | Necrosis |
| D003327 | Coronary Disease |
| D001161 | Arteriosclerosis |
| D001157 | Arterial Occlusive Diseases |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |