Back to resultsMetformin and Prevention of Cardiovascular Events in Patients With Acute Myocardial Infarction and Prediabetes (MIMET) (MIMET)
Primary Purpose
PreDiabetes, Acute Myocardial Infarction, Non ST Elevation Myocardial Infarction
Status
Recruiting
Phase
Phase 3
Locations
Sweden
Study Type
Interventional
Intervention
Metformin
Sponsored by
About this trial
This is an interventional prevention trial for PreDiabetes
Eligibility Criteria
Inclusion Criteria:
I. AMI
II. Swedish citizens with a personal ID number ≥18 years and ≤80 years
III. Newly diagnosed prediabetes:
- HbA1c 42-47 mmol/mol or
- Capillary or venous fasting plasma glucose concentration 6.1-6.9 mmol/L or
- 2-hour post-load capillary glucose concentration 8.9-12.1 mmol/L or
- 2-h post-load venous plasma glucose concentration 7.8-11.0 mmol/L
- 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
Sites / Locations
- Medicinkliniken, Ljungby HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
No Intervention
Arm Label
Metformin on top of standard care
Standard care alone
Arm Description
Metformin will be prescribed by the Investigator at the study site and dispensed at pharmacy of choice by the patient. Metformin will be recommended to be gradually titrated to minimize gastrointestinal side effects with a start dose of 500 mg 1x1 for 1 week and thereafter 500 mg 1x2 with an individualised target dose of 2000 mg daily depending on tolerability. The goal is to a have minimal dose of 500 mg 1x2. Patients will be informed to stop medication in events of sever nausea, vomiting or dehydration according to standard practice. The threshold for metformin titration or adding another drug during follow-up is recommended to be assessed individually by the Investigator at the study site, responsible for the patient. Patients with eGFR <60 cannot be included in the MIMET study. If GFR is between 30-45 ml/min during the study, metformin should be reduced to 1000 mg daily. Metformin is contraindicated if GFR <30 ml/min. Standard care will be the same as in the control arm.
Standard care according to national guidelines. In Sweden there is no pharmacological intervention recommended for individuals with prediabetes at present. Standard care includes diet and life-style advice, which will be given to both groups in the same manner according to local routines, based on the present guidelines. Secondary preventive treatment includes physical activity, participating in exercise program, dietary habits, BMI and or waist circumference, smoking and EQ-5D will be followed in accordance with the routinely reported SWEDEHEART-SEPHIA variables.
Outcomes
Primary Outcome Measures
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).
Secondary Outcome Measures
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.
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).
All-cause death
Time to all-cause death
CV death
Time to CV death
Hospitalisation with MI
Time to readmission for MI. Hospital admission for MI during day 0-30 after index AMI will be excluded
Hospitalisation with stroke
Time to hospitalisation for stroke (main diagnosis)
Hospitalisation with heart failure
Time to hospitalisation for heart failure (main diagnosis)
New cancer diagnosis
Time to new cancer diagnosis defined as the first occurrence of any cancer in the National Patient Register
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)
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
Full Information
NCT ID
NCT05182970
First Posted
December 21, 2021
Last Updated
December 21, 2021
Sponsor
Karolinska Institutet
Collaborators
Capio Sankt Görans Hospital, Uppsala University, The Swedish Research Council
1. Study Identification
Unique Protocol Identification Number
NCT05182970
Brief Title
Metformin and Prevention of Cardiovascular Events in Patients With Acute Myocardial Infarction and Prediabetes (MIMET)
Acronym
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
Study Type
Interventional
2. Study Status
Record Verification Date
December 2021
Overall Recruitment Status
Recruiting
Study Start Date
December 2, 2021 (Actual)
Primary Completion Date
May 2026 (Anticipated)
Study Completion Date
May 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Karolinska Institutet
Collaborators
Capio Sankt Görans Hospital, Uppsala University, The Swedish Research Council
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No
5. Study Description
Brief 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).
Detailed 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
PreDiabetes, Acute Myocardial Infarction, Non ST Elevation Myocardial Infarction, ST Elevation Myocardial Infarction
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
5160 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Metformin on top of standard care
Arm Type
Active Comparator
Arm Description
Metformin will be prescribed by the Investigator at the study site and dispensed at pharmacy of choice by the patient. Metformin will be recommended to be gradually titrated to minimize gastrointestinal side effects with a start dose of 500 mg 1x1 for 1 week and thereafter 500 mg 1x2 with an individualised target dose of 2000 mg daily depending on tolerability. The goal is to a have minimal dose of 500 mg 1x2. Patients will be informed to stop medication in events of sever nausea, vomiting or dehydration according to standard practice. The threshold for metformin titration or adding another drug during follow-up is recommended to be assessed individually by the Investigator at the study site, responsible for the patient. Patients with eGFR <60 cannot be included in the MIMET study. If GFR is between 30-45 ml/min during the study, metformin should be reduced to 1000 mg daily. Metformin is contraindicated if GFR <30 ml/min. Standard care will be the same as in the control arm.
Arm Title
Standard care alone
Arm Type
No Intervention
Arm Description
Standard care according to national guidelines. In Sweden there is no pharmacological intervention recommended for individuals with prediabetes at present. Standard care includes diet and life-style advice, which will be given to both groups in the same manner according to local routines, based on the present guidelines. Secondary preventive treatment includes physical activity, participating in exercise program, dietary habits, BMI and or waist circumference, smoking and EQ-5D will be followed in accordance with the routinely reported SWEDEHEART-SEPHIA variables.
Intervention Type
Drug
Intervention Name(s)
Metformin
Intervention Description
Individualised target dose of 2000 mg daily depending on tolerability.
Primary Outcome Measure Information:
Title
Time to major CV event
Description
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).
Time Frame
Estimated follow-up for each patient is 1-4 years
Secondary Outcome Measure Information:
Title
Time to the composite endpoint CV death, main diagnosis of MI, heart failure or stroke.
Description
Time to first event included in the composite endpoint CV death, main diagnosis of MI, heart failure or stroke.
Time Frame
Estimated follow-up for each patient is 1-4 years
Title
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).
Description
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).
Time Frame
Estimated follow-up for each patient is 1-4 years
Title
All-cause death
Description
Time to all-cause death
Time Frame
Estimated follow-up for each patient is 1-4 years
Title
CV death
Description
Time to CV death
Time Frame
Estimated follow-up for each patient is 1-4 years
Title
Hospitalisation with MI
Description
Time to readmission for MI. Hospital admission for MI during day 0-30 after index AMI will be excluded
Time Frame
Estimated follow-up for each patient is 1-4 years
Title
Hospitalisation with stroke
Description
Time to hospitalisation for stroke (main diagnosis)
Time Frame
Estimated follow-up for each patient is 1-4 years
Title
Hospitalisation with heart failure
Description
Time to hospitalisation for heart failure (main diagnosis)
Time Frame
Estimated follow-up for each patient is 1-4 years
Title
New cancer diagnosis
Description
Time to new cancer diagnosis defined as the first occurrence of any cancer in the National Patient Register
Time Frame
Estimated follow-up for each patient is 1-4 years
Title
Initiation of any glucose lowering therapy
Description
Time to initiation of any glucose lowering therapy (ATC code A10 in the Prescribed Drug Register, excluding randomisation to metformin)
Time Frame
Estimated follow-up for each patient is 1-4 years
Title
Diabetes diagnosis
Description
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
Time Frame
Estimated follow-up for each patient is 1-4 years
Other Pre-specified Outcome Measures:
Title
Serious Adverse Events
Description
Number of Serious Adverse Events with at least a possible relationship to the study medication
Time Frame
Estimated follow-up for each patient is 1-4 years
Title
Lactic acidosis (E11.1D)
Description
Number of events of lactic acidosis
Time Frame
Estimated follow-up for each patient is 1-4 years
Title
Hypoglycaemia
Description
Number of events of hypoglycaemia
Time Frame
Estimated follow-up for each patient is 1-4 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
I. AMI
II. Swedish citizens with a personal ID number ≥18 years and ≤80 years
III. Newly diagnosed prediabetes:
HbA1c 42-47 mmol/mol or
Capillary or venous fasting plasma glucose concentration 6.1-6.9 mmol/L or
2-hour post-load capillary glucose concentration 8.9-12.1 mmol/L or
2-h post-load venous plasma glucose concentration 7.8-11.0 mmol/L
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Anna Norhammar, MD, Prof.
Phone
+46858701568
Email
anna.norhammar@ki.se
First Name & Middle Initial & Last Name or Official Title & Degree
Viveca Ritsinger, MD, PhD
Phone
+46372585000
Email
viveca.ritsinger@ki.se
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Anna Norhammar, MD, Prof.
Organizational Affiliation
Karolinska Institutet
Official's Role
Principal Investigator
Facility Information:
Facility Name
Medicinkliniken, Ljungby Hospital
City
Ljungby
ZIP/Postal Code
341 35
Country
Sweden
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Helena Otteborn, Head of Clinic
First Name & Middle Initial & Last Name & Degree
Viveca Ritsinger, MD PhD
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Metformin and Prevention of Cardiovascular Events in Patients With Acute Myocardial Infarction and Prediabetes (MIMET)
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