Prasugrel Versus High Dose Clopidogrel in Clopidogrel Resistant Patients Undergoing Chronic Hemodialysis

Study Overview
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Brief Summary
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Clopidogrel administration is essential in patients undergoing percutaneous coronary intervention, in patients with previous stroke, in patients under chronic hemodialysis via fistulae and in patients with chronic atrial fibrillation if coumarin administration is not a viable option. Patients with chronic renal failure present lower clopidogrel response compared to those with normal renal function. Additionally, hemodialysis via the dialysis filter causes a decrease in glycoprotein platelet receptors, potentially associated with thienopyridine hyporesponsiveness. Clopidogrel resistant patients as assessed by VerifyNow P2Y12(Accumetrics)will be randomized in 1:1 fashion to prasugrel 10mg/day or clopidogrel 150mg/day. On day 15±2 days a crossover directly to the alternate treatment group will be carried out, without an interventing washout period. All patients will undergo platelet reactivity assessment, documentation of major adverse cardiac events and documentation of any serious adverse events(stroke, bleeding)at day 15 and day 30.

Official Title
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Prasugrel in Comparison to High Clopidogrel Dose for Inhibition of Platelet Reactivity as Assessed With a Point-of-Care Platelet Function Assay in Patients Undergoing Chronic Hemodialysis Presenting Resistance to the Usual Clopidogrel Dose

Conditions
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Hemodialysis, Chronic Renal Failure

Intervention / Treatment
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* Drug: Prasugrel
* Drug: Clopidogrel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years old History of chronic renal failure under hemodialysis for at least 6 months Under clopidogrel 75mg/day treatment for at least 7 days before randomization Informed consent obtained in writing Exclusion Criteria: Treatment with other investigational agents (including placebo) or devices within 30 days prior to randomization or planned use of investigational agents or devices prior to the Day 30 visit. Pregnancy Breastfeeding Inability to give informed consent or high likelihood of being unavailable for the Day 30 follow up. Malignancy Acute coronary syndrome or hemodynamic instability within 30 days prior to randomization Requirement for oral anticoagulant prior to the Day 30 visit Requirement for discontinuation of thienopyridine treatment prior to the Day 30 visit Treatment with IIb/IIIa inhibitors within 30 days prior to randomization or planned administration prior to the Day 30 visit Known hypersensitivity to prasugrel or clopidogrel. History of gastrointestinal bleeding, genitourinary bleeding or other site abnormal bleeding within the previous 6 months. Other bleeding diathesis, or considered by investigator to be at high risk for bleeding on thienopyridine therapy. Any previous history of ischemic stroke, intracranial hemorrhage or disease (neoplasm, arteriovenous malformation, aneurysm). Thrombocytopenia (<100.000 / μL) at randomization Known liver failure (bilirubin > 2mg/dl)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Prasugrel<br>Prasugrel per os 10 mg/day | Drug: Prasugrel<br>* Prasugrel 10 mg/day for 15 days<br>|
| Active Comparator: Clopidogrel<br>Clopidogrel per os 150 mg/day | Drug: Clopidogrel<br>* Clopidogrel 150 mg/day for 15 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Platelet Reactivity Units (PRU)assessed by VerifyNow P2Y12(Accumetrics) |  | Day 30 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major Adverse Cardiac Events (death, myocardial infarction, revascularization) |  | Day 30 | 
| Hemorrhage |  | Day 30 | 
| Stroke |  | Day 30 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Clopidogrel Resistance, prasugrel, Hemodialysis