Pioglitazone Protects Diabetes Mellitus (DM) Patients Against Re-Infarction (PPAR Study)

Study Overview
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Brief Summary
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To evaluate whether the pioglitazone could reduce the recurrence of myocardial infarction (MI) in patients with DM and old myocardial infarction

Detailed Description
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Type 2 diabetes mellitus is a well-established risk factor for coronary heart disease and atherosclerotic change in coronary artery. So we designed a prospective randomized multi-center trial named the pioglitazone could reduce the recurrence of myocardial infarction in patients with DM and myocardial infarction(PPAR study) to evaluate whether pioglitazone could reduce the recurrence of myocardial infarction in patients with DM(HbA1c<6.5%) and myocardial infarction. More than 100 hospitals will participate in the PPAR study. Patients with DM who have history of prior myocardial infarction are randomly allocated to receive pioglitazone or (1)instructs weight reduction, appropriate diet, regular exercise and/or (2)prescribes sulfonylurea agents. The number of patients to be recruited is 720 and this study will continue at least 2 years until 7 year or the end of the study. The primary end-points are (1) cardiovascular mortality and (2) hospitalization for cardiovascular events. Effects in suppression of new diabetes development also will be evaluated. We should recognize DM as important therapeutic target to decrease recurrence of cardiovascular events. PPAR study, a large scale multi-center trial in Japan, will provide us new evidence how to treat DM patients with prior myocardial infarction.

Official Title
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The Japan Working Group for the Assessment That the Pioglitazone Protects DM Patients Against Re-Infarction

Conditions
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Diabetes Mellitus, Myocardial Infarction

Intervention / Treatment
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* Drug: pioglitazone
* Other: control


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: diabetes mellitus (fasting plasma glucose levels of>126 mg/dL, or 2-hour 75g oral glucose tolerance test (OGTT) value of >200 mg/dL, and HbA1c levels of<6.5% (47.5 IFCC)) History of myocardial infarction Age between 20-79 years old Exclusion Criteria: acute MI occurring within the last 7 days New York Heart Association (NYHA) symptoms of no fewer II or with left ventricular ejection fraction of not more than 40% suspected type I DM scheduled coronary angioplasty or history of coronary artery bypass graft surgery serious liver or kidney damage history of allergy or drug hypersensitivity arteriosclerosis obliterans with Fontaine stage III or worse inability to understand and/or comply with study medications, procedures and/or follow-up or any conditions that may render the patient unable to complete the study in the opinion of the investigator.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 79 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Pioglitazone<br>Participants in the pioglitazone group were administered a pioglitazone tablet (15 mg) once a day. In the event of the side effects such as oedema, the dosage of pioglitazone was reduced to half or a quarter of the original dosage. Otherwise, we tried to increase the dose of pioglitazone to 30mg/day. | Drug: pioglitazone<br> <br> |
| Active Comparator: Control<br>Participants assigned to Control group were treated with diet and exercise therapy or sulfonylurea (SU) or other additional drugs than pioglitazone. | Other: control<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The time till the first cardiovascular composite endpoint | death from cardiovascular death, and the hospitalization due to nonfatal myocardial infarction, nonfatal unstable angina25, treatment with coronary revascularisation (percutaneous coronary intervention or coronary artery bypass graft) and cerebral infarction. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All cause mortality | death of any cause | 2 years | 
| Hospitalization due to nonfatal myocardial infarction | nonfatal myocardial infarction | 2 years | 
| Hospitalization due to nonfatal unstable angina | nonfatal unstable angina | 2 years | 
| Hospitalization due to treatment with coronary revascularisation (percutaneous coronary intervention or coronary artery bypass graft) | coronary revascularisation | 2 years | 
| Hospitalization due to cerebral infarction | cerebral infarction | 2 years | 
| The progression of DM | HbA1C levels>7.0% | 2 years | 
| worsening of renal function | serum creatine levels>2.5mg/dL or the increases of serum creatine levels by >2mg/dL | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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diabetes mellitus, myocardial infarction, pioglitazone