Dual Antiplatelet Therapy Tailored on the Extent of Platelet Inhibition

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy (reduction of major ischemic events at 6 and 12 months of follow-up) of a tailored clopidogrel therapy in patients with UA/NSTEMI undergoing PCI with stent implantation and wiht a documented residual platelet reactivity assessed by a point of care system (VerifyNow P2Y12).

Detailed Description
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Several studies documented the presence of a high variability in the individual response to antiplatelet therapies in terms of extent of platelet function inhibition. This laboratory finding is the so-called aspirin or clopidogrel resistance which we prefer to define residual platelet reactivity (RPR) on antiplatelet therapy. A growing body of evidence is demonstrating the clinical relevance of this laboratory parameter, i.e. patients with RPR are at higher risk of a subsequent adverse cardiovascular event. In particular, it has been demonstrated that RPR measured by light transmittance aggregometry induced by ADP or by the point of care assay VerifyNow P2Y12 identifies patients which, after coronary revascularization with stent implantation, at higher risk of a potentially catastrophic event such as stent thrombosis. No randomized trials are available in the literature on the efficacy and safety of an antiplatelet therapy tailored on the extent of platelet function inhibition.

Official Title
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Optimization of Antiplatelet Therapy With Clopidogrel on the Basis of the Extent of Platelet Inhibition in Patients With Acute Coronary Syndromes on Dual Antiplatelet Therapy Undergoing PCI With Stent Implantation

Conditions
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Unstable Angina, NSTEMI

Intervention / Treatment
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* Drug: comparison of different dosage of clopidogrel
* Drug: doubled therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Unstable or NSTEMI Exclusion Criteria: Previous bleeding events which have required blood transfusion PT- INR >1.5 Platelet count ≤ 100000/ mm3 Hb < 10 g/dl Previous TIA/stroke (ischemic or hemorrhagic or unknown) Body weight < 60 Kg Creatinine levels ≥ 4 mg/dl Cerebral neoplasia Recent major trauma/surgery/head injury (within 3 previous weeks) Gastrointestinal hemorrhage in the last month Aortic dissection Known haemorrhagic diathesis Oral anticoagulant therapy Pregnancy or 1 week after delivery Uncontrolled hypertension (systolic >180 mmHg or diastolic >110 mmHg) Severe liver disease Infective endocarditis Major psychiatric disorders Alcool or drug abuse Active peptic ulcer Noncompressible arterial puncture within 14 days Prolonged cardiopulmonary resuscitation

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 90 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: 1: standard therapy<br>clopidogrel 75 mg/day | Drug: comparison of different dosage of clopidogrel<br>* clopidogrel 75 mg/day versus clopidogrel 150 mg/day<br>|
| Active Comparator: 2: doubled therapy<br>clopidogrel 150 mg/day | Drug: doubled therapy<br>* clopidogrel 150 mg/day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of MACE (cardiovascular death, nonfatal myocardial infarction, target lesion vessel revascularization by PCI or coronary bypass) |  | 6 and 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Stent thrombosis with angiographic confirmation; platelet function assessed by VerifyNow P2Y12 1 week after the randomization |  | 1 week; 6 and 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Clopidogrel therapy, platelet function inhibition