Metformin and Prevention of Cardiovascular Events in Patients With Acute Myocardial Infarction and Prediabetes (MIMET)

Acute Myocardial Infarction Clinical Trial

— MIMET  

Official title:

The Myocardial Infarction and New Treatment With Metformin Study (MIMET) - a R-RCT to Study Metformin and the Prevention of Cardiovascular Events in Patients With Acute Myocardial Infarction and Newly Detected Prediabetes

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05182970
• Other study ID #: 2019-05382
• Status: Recruiting
• Phase: Phase 3
• Start date: December 2, 2021
• Est. completion date: May 2026

Study information

• Verified date: April 2024
• Source: Karolinska Institutet
• Contact: Anna Norhammar, MD, Prof.
• Phone: +46858701568
• Email: anna.norhammar[@]ki.se
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Prediabetes is associated to an increased risk of cardiovascular disease and mortality. Although metformin can delay progression to diabetes there is a lack of RCTs evaluating the effect of metformin on cardiovascular outcomes. MIMET aims to investigate if addition of metformin to standard care has effects on the occurrence of cardiovascular events after acute myocardial infarction in patients with newly detected prediabetes (identified by oral glucose tolerance test, HbA1c or fasting glucose levels).

Description:

The study is a national multicenter R-RCT associated to the The Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies (SWEDEHEART registry) where participants, after informed consent, will be randomly assigned to either open treatment with standard care + metformin or standard care alone in a 1:1 ratio. Standard care consists of diet and life-style advice according to national guidelines but does not include metformin. Baseline data for individual patients will be collected from the SWEDEHEART registry. Patients will be followed per routine care at 2 and 12 months post index AMI and in addition at a final study visit at 24 months. Laboratory measurements and collection of SAE will be performed yearly. In total n=5150 patients is expected to be followed for major CV event (all-cause mortality, myocardial infarction, heart failure and stroke) by linkage with SWEDEHEART and national health registries.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 5160
• Est. completion date: May 2026
• Est. primary completion date: May 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

I. AMI II. Swedish citizens with a personal ID number =18 years and =80 years

III. Newly diagnosed prediabetes:

1. HbA1c 42-47 mmol/mol or

2. Capillary or venous fasting plasma glucose concentration 6.1-6.9 mmol/L or

3. 2-hour post-load capillary glucose concentration 8.9-12.1 mmol/L or

4. 2-h post-load venous plasma glucose concentration 7.8-11.0 mmol/L

5. HbA1c <48 mmol/mol and 2-hour post-load capillary glucose concentration >12.1 mmol/L or 2-h post-load venous plasma glucose concentration >11.0 mmol/L (thus elevated 2-hour glucose levels in the diabetes range but without HbA1c levels diagnostic for diabetes) IV. Naïve to metformin and other glucose lowering therapy V. Signed informed consent Exclusion Criteria: I. Type 1 diabetes II. Known type 2 diabetes III. Indication for glucose lowering treatment IV. Acute condition with high risk for volume depletion, circulatory shock, hypoxia V. Serious illness, other than cardiovascular, with short life expectancy VI. Renal failure (eGFR <60ml/min) VII. Hepatic failure VIII. Malignancy within the last year IX. Contraindication or hypersensitivity to the study drug X. Alcohol or drug abuse XI. Pregnancy or breastfeeding XII. Women of childbearing potential without adequate anticonception during any part of the study period XIII. Previous hospitalisation for lactic acidosis XIV. Predicted inability to comply with the study protocol

Related Conditions & MeSH terms

• Acute Myocardial Infarction
• Glucose Intolerance
• Infarction
• Myocardial Infarction
• Non ST Elevation Myocardial Infarction
• Non-ST Elevated Myocardial Infarction
• PreDiabetes
• Prediabetic State
• ST Elevation Myocardial Infarction

Intervention

Drug:
• Metformin
Individualised target dose of 2000 mg daily depending on tolerability.

Locations

Country	Name	City	State
Sweden	Medicinkliniken, Ljungby Hospital	Ljungby

Sponsors (4)

Lead Sponsor	Collaborator
Karolinska Institutet	Capio Sankt Görans Hospital, The Swedish Research Council, Uppsala University

Country where clinical trial is conducted

Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Serious Adverse Events	Number of Serious Adverse Events with at least a possible relationship to the study medication	Estimated follow-up for each patient is 1-4 years
Other	Lactic acidosis (E11.1D)	Number of events of lactic acidosis	Estimated follow-up for each patient is 1-4 years
Other	Hypoglycaemia	Number of events of hypoglycaemia	Estimated follow-up for each patient is 1-4 years
Primary	Time to major CV event	Major CV event; a composite endpoint of first of all-cause death or main diagnosis of MI, heart failure or stroke (reported in SWEDEHEART, the National Patient Register and the Cause of Death Register).	Estimated follow-up for each patient is 1-4 years
Secondary	Time to the composite endpoint CV death, main diagnosis of MI, heart failure or stroke.	Time to first event included in the composite endpoint CV death, main diagnosis of MI, heart failure or stroke.	Estimated follow-up for each patient is 1-4 years
Secondary	Time to the composite endpoint of all-cause death, main diagnosis of MI, stroke and revascularisation (CABG or PCI >4 months after the index AMI).	Time to first event included in the composite endpoint of all-cause death, main diagnosis of MI, stroke and revascularisation (CABG or PCI >4 months after the index AMI).	Estimated follow-up for each patient is 1-4 years
Secondary	All-cause death	Time to all-cause death	Estimated follow-up for each patient is 1-4 years
Secondary	CV death	Time to CV death	Estimated follow-up for each patient is 1-4 years
Secondary	Hospitalisation with MI	Time to readmission for MI. Hospital admission for MI during day 0-30 after index AMI will be excluded	Estimated follow-up for each patient is 1-4 years
Secondary	Hospitalisation with stroke	Time to hospitalisation for stroke (main diagnosis)	Estimated follow-up for each patient is 1-4 years
Secondary	Hospitalisation with heart failure	Time to hospitalisation for heart failure (main diagnosis)	Estimated follow-up for each patient is 1-4 years
Secondary	New cancer diagnosis	Time to new cancer diagnosis defined as the first occurrence of any cancer in the National Patient Register	Estimated follow-up for each patient is 1-4 years
Secondary	Initiation of any glucose lowering therapy	Time to initiation of any glucose lowering therapy (ATC code A10 in the Prescribed Drug Register, excluding randomisation to metformin)	Estimated follow-up for each patient is 1-4 years
Secondary	Diabetes diagnosis	Defined as diabetes diagnosis in National Patient Register and/or prescribed glucose lowering treatment in the Prescribed Drug Register excluding randomisation to metformin in the active treatment arm	Estimated follow-up for each patient is 1-4 years