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
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 5,160
- 试验地点
- 1
- 主要终点
- Time to major CV event
研究概览
简要总结
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).
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Metformin on top of standard care
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.
干预措施: Metformin (Drug)
结局指标
主要结局
Time to major CV event
时间窗: Estimated follow-up for each patient is 1-4 years
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).
次要结局
- New cancer diagnosis(Estimated follow-up for each patient is 1-4 years)
- Time to the composite endpoint CV death, main diagnosis of MI, heart failure or stroke.(Estimated follow-up for each patient is 1-4 years)
- 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).(Estimated follow-up for each patient is 1-4 years)
- Hospitalisation with MI(Estimated follow-up for each patient is 1-4 years)
- Hospitalisation with heart failure(Estimated follow-up for each patient is 1-4 years)
- All-cause death(Estimated follow-up for each patient is 1-4 years)
- CV death(Estimated follow-up for each patient is 1-4 years)
- Hospitalisation with stroke(Estimated follow-up for each patient is 1-4 years)
- Initiation of any glucose lowering therapy(Estimated follow-up for each patient is 1-4 years)
- Diabetes diagnosis(Estimated follow-up for each patient is 1-4 years)
研究者
Anna Norhammar
Professor
Karolinska Institutet