High Clopidogrel Dose Versus Prasugrel and Ticagrelor in High Reactive Stable Patients

Study Overview
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Brief Summary
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Dual antiplatelet therapy with Aspirin and Clopidogrel for at least one year is essential in patients following an acute coronary syndrome (ACS) or percutaneous coronary intervention (PCI) with drug eluting stent(s) implantation. Interindividual variability in platelet response to Clopidogrel has been reported, with several mechanisms (intrinsic high platelet reactivity [PR], variability of the drug metabolism, and various drug interactions) being implicated for high post-Clopidogrel treatment PR. The investigators aim to perform a prospective, single-center, investigator-initiated, randomized, study to compare platelet inhibition by Prasugrel 10 mg/day, Ticagrelor (90 mg twice daily) and high-dose 150 mg/day Clopidogrel in patients with High on-treatment platelet reactivity (HTPR) with standard dose of Clopidogrel. Patients with HTPR (defined as area under curve-AUC ≥ 450 or > 45 Unit) and with loss-of-function allele CYP2C19*2 will be enrolled in the study and will be randomized (Day 0) in a 1:1:1 ratio, to either Clopidogrel 150 mg a day or Prasugrel 10 mg a day or Ticagrelor (90 mg twice daily) until Day-15 and-30 post randomization.

Official Title
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Comparison of Therapy With TICAGRELOR, Prasugrel and High Clopidogrel Dose in PCI Patients With High on Treatment Platelet Reactivity and Genotype Variation

Conditions
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Coronary Artery Disease

Intervention / Treatment
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* Drug: Clopidogrel
* Drug: Prasugrel
* Drug: Ticagrelor


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: patients underwent to percutaneous coronary intervention (PCI) clopidogrel resistance after Platelet reactivity blood test Exclusion Criteria: history of bleeding diathesis chronic oral anticoagulation treatment contraindications to antiplatelet therapy PCI or coronary artery bypass grafting (CABG) < 3 months hemodynamic instability platelet count < 100,000/μl hematocrit < 30% creatinine clearance < 25 ml/min Patients with a history of stroke contraindication for prasugrel administration patients weighing < 60 kg > 75 years of age.

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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Prasugrel standard dose<br>Patient will be randomized to this intervention will receive in the first time prasugrel and after 15 days and 30 days we will control the responsivness of the study drug. | Drug: Prasugrel<br>* Patient will be randomized to this intervention will receive in the first time prasugrel and after 15 days and 30 days we will control the responsivness of the study drug.<br>|
| Experimental: high clopidogrel dose<br>Patient will be randomized to this intervention will receive in the first time the high clopidogrel dose and after 15 days and 30 days we will control the responsivness of the study drug. | Drug: Clopidogrel<br>* Patient will be randomized to this intervention will receive in the first time the double dose of clopidogrel and after 15 days and 30 days we will control the responsivness of the study drug.<br>|
| Experimental: Ticagrelor standard dose<br>Patient will be randomized to this intervention will receive in the first time ticagrelor and after 15 days and 30 days we will control the responsivness of the study drug. | Drug: Ticagrelor<br>* Patient will be randomized to this intervention will receive in the first time Ticagrelor and after 14 days and 28 days we will change their therapy with the high clopidogrel dose or Prasugrel (dual crossover).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| antiplatelet effect of standard dose of prasugrel or ticagrelor versus high dose clopidogrel in stable patients with high reactivity | the antiplatelet effect in terms of level platelet reactivity (< 450 Area under the curve (AU*min)) of standard dose of Prasugrel (10 mg/day) either Ticagrelor (90 mg twice daily) versus high dose Clopidogrel (150 mg/day) in patients undergoing PCI with high reactivity | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bleeding (major, minor, or minimal) | Bleeding (major, minor, or minimal) | 45 days | 
| Major Adverse Cardiac Cerebrovascular Events | cardiovascular death, myocardial infarction, and stroke | 45 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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antiplatelet effect, prasugrel, clopidogrel, stable angina