Incidence of Major Cardiovascular Events in Diabetic Patients With ACS Undergoing Coronary Angioplasty and Treated With Clopidogrel 150 mg Versus 75 mg

Study Overview
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Brief Summary
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Acute Coronary Syndrome (ACS) is triggered by the rupture of an atherosclerotic plaque that results in a platelet aggregation reaction in the coronary artery. The administration of antiplatelet agents starting from the acute phase of the disease has helped reduce the risk of ischemic relapse both during initial and long-term hospitalization. Management of clopidogrel following an ischemic event has been the subject of several treatment regimens ranging from a single continuous dose to a sequential double dose of between 7 and 30 days. The CURRENT-OASIS 7 therapeutic trial showed a benefit of clopidogrel double dose in reducing the risk of myocardial intervention (MI) and the composite outcome: cardiovascular mortality, MI, or stroke (CVA/TIA) at 30 days. However, the study protocol was interested in all ACSs, regardless of the Type 2 Diabetes Mellitus (T2DM) status in selected patients. Also, doubling of clopidogrel dose was maintained over 7 days after angioplasty. The literature describes an increased cardiovascular risk in type II diabetics in secondary prevention. No previous study has evaluated the effect of clopidogrel double dose given for 1 month on the reduction of this risk in the long-term in diabetic patients. Thus, the objective of this study is to evaluate the efficacy and safety of clopidogrel double dose, given for 1 month in ACS in the diabetic patient.

Detailed Description
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The study is an open label, multicentric clinical trial. Collected data are managed by the DACIMA Clinical Suite®, the electronic data capture platform which complies with the FDA 21 CFR part 11 requirements (Food and Drug Administration 21 Code of Federal Regulations part 11), the HIPAA specifications (Health Insurance Portability and Accountability Act), and the ICH standards (International Conference on Harmonisation).

Official Title
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Incidence Des évènements cArdiovasculaires majeurS Chez Les Patients COronariens diabétiques Subissant Une angioPlastie Coronaire et traités Par Clopidogrel à la Dose 150 mg Versus 75 mg

Conditions
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Diabetes Mellitus, Type 2, NSTEMI - Non-ST Segment Elevation MI, Coronary Angioplasty

Intervention / Treatment
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* Drug: Clopidogrel


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Male or female aged between 18 to 75 years old. Proven ACS requiring PTCA within 1 week of inclusion. The ACS should be without ST-segment elevation (presence of chest pain with ST-segment or T-wave changes without sustained ST segment elevation) with elevation of cardiac biomarkers of MI (positive troponins). Coronary angiography showing at least one coronary lesion, whether mono, bi or multi-truncate Type 2 diabetes confirmed for at least one year Patient candidate for treatment with Clopidogrel Informed consent of patients Non-Inclusion Criteria: Non-consenting patient and/or participating in another clinical study ACS with ST segment elevation (STEMI) History of digestive or cerebral bleeding with antiplatelet agents or anticoagulants Insulin-dependent diabetes mellitus (IDDM) Diabetic requiring insulin Patient in cardiogenic shock Patient under treatment with anti-glycoprotein IIb/IIIa or stopped less than 72 hours prior to inclusion Previously treated with clopidogrel or thrombolytics Patients programmed for surgery in less than 6 months Ischemic stroke less than 6 weeks old History of haemorrhagic stroke (regardless of time) Patients under or candidates for Vitamin K antagonist (VKA) Patients under another antiplatelet agent (Ticlopidine, Prasugrel) Patients with a contraindication to clopidogrel (hypersensitivity to the active substance or to any of the excipients, severe hepatic impairment, progressive hemorrhagic lesion such as peptic ulcer or intracranial hemorrhage) Under omeprazole treatment, or considered during the study Anemia (Hb <12g/dl) Thrombocytopenia with less than 100000 cells/mm3 Serum creatinine greater than 200 μmol/l Pregnancy and/or breast-feeding Severe renal impairment Exclusion criteria: Non-compliance with treatment (treatment compliance <80%) AE/SAE requiring cessation of treatment Planning a CABG Occurrence of pregnancy during the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A comparative, interventional, multicenter, randomized, prospective, two-arm study with monotherapy in two different doses
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm 1 (single dose)<br>Will receive a clopidogrel loading dose of 600 mg PO, then a daily dose of clopidogrel 75 mg PO until the angioplasty is performed. After coronary intervention, a daily dose of clopidogrel 150 mg PO for 7 days will be given, followed by a daily single dose of clopidogrel (75 mg PO) for 21 days. Maintenance therapy will be clopidogrel daily dose of 75 mg PO thereafter, until the end of the study. | Drug: Clopidogrel<br>* COPIGREL® - clopidogrel dosed at 75 mg per tablet<br>* Other names: COPIGREL®;|
| Active Comparator: Arm 2 (double dose)<br>Will receive a clopidogrel loading dose of 600 mg PO, then a daily dose of clopidogrel 75 mg PO until the angioplasty is performed. After coronary intervention, a daily dose of clopidogrel 150 mg PO for 7 days will be given, followed by a daily double dose of clopidogrel (150 mg PO) for 21 days. Maintenance therapy will be clopidogrel daily dose of 75 mg PO thereafter, until the end of the study. | Drug: Clopidogrel<br>* COPIGREL® - clopidogrel dosed at 75 mg per tablet<br>* Other names: COPIGREL®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major Cardiovascular Events (MACE) | Incidence of major cardiovascular events including cardiac death, MI, cerebrovascular accident (CVA), revascularization (PTCA, GABG), stent thrombosis. | 1 year after coronary intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bleeding Events | All bleeding events (digestive, cerebral, other locations) | At 1, 3, 6, 9 and 12 months from patient enrollment | 
| Heart Failure Readmission | Incidence of heart failure hospital readmissions | At 1, 3, 6, 9 and 12 months from patient enrollment | 
| Global Death | Incidence of death of all causes (death of cardiovascular origin and death of non-cardiovascular origin) | At 1, 3, 6, 9 and 12 months from patient enrollment | 
| Incidence of Adverse Events | Incidence of Adverse Events (AE) including Serious Adverse Events (SAE) | At 1, 3, 6, 9 and 12 months from patient enrollment |