Clinical trial NCT01465828: Therapy With High Clopidogrel Dose or Prasugrel Standard Dose Reduces the Platelet Reactivity in Patients With Genotype Variation RESET GENE Trial
Official title: PhaRmacodynamic Effects of Switching thErapy in paTients With High on Treatment Platelet Reactivity and Genotype Variation: High Clopidogrel Dose Versus Prasugrel RESET GENE Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Acute Coronary Syndrome
Keywords: antiplatelet effect
prasugrel
clopidogrel
ACS
Lead sponsor: University of Roma La Sapienza
Sponsor class: OTHER
First posted: 2011-11-06
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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. Interindividual variability in platelet response to clopidogrel has been reported, with several mechanisms being implicated for high post-clopidogrel treatment PR. High on-treatment platelet reactivity (HTPR) is associated with an increased risk of adverse events after PCI. Studies in patients on chronic clopidogrel treatment are scarce, mainly in diabetic patients where HTPR is frequently present and independently predictive of adverse events. Optimization of platelet inhibition in patients with HTPR by increasing clopidogrel or alternatively, by more potent P2Y12 inhibitors is a controversial issue, mostly studied in post PCI patients, while no data exist, to the best of the investigators knowledge, in stable patients on chronic clopidogrel treatment. Therefore all HTPR patients, that will accept to participate, will be enrolled will randomize (Day 0) in a 1:1 ratio to either clopidogrel 150 mg a day, or prasugrel 10 mg a day, until Day 14 post randomization. A 14 ± 2 day visit will be performed for PR measurement and safety evaluation, with the blood sample being will be obtained 16-18 hours after the last study-drug dose, will follow by crossover directly to the alternate therapy for an additional 14 days without an intervening washout period. At Day 28 ± 2 patients will return for the clinical and laboratory assessment as did on Day 14 visit.


Eligibility criteria: Inclusion Criteria:

* patients underwent to PCI
* lopidogrel 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.

Primary outcomes:
measure: antiplatelet effect of standard dose of prasugrel versus high dose clopidogrel in stable patients with HTPR
timeFrame: 14-28 days
Secondary outcomes:
measure: Bleeding (major, minor, or minimal according to the TIMI study criteria)
timeFrame: 14-28 days
measure: Major Adverse Cardiac Cerebrovascular Events
timeFrame: 14-28 days
Other outcomes:
Locations:
city: Roma
country: Italy
facility: Dept.of Cardiovascular Sciences,Policlinico Umberto I
city: Rome
country: Italy
facility: Dept.of Cardiovascular Sciences,Policlinico Umberto I
Study officials:
References:
citation: Sardella G, Calcagno S, Mancone M, Palmirotta R, Lucisano L, Canali E, Stio RE, Pennacchi M, Di Roma A, Benedetti G, Guadagni F, Biondi-Zoccai G, Fedele F. Pharmacodynamic effect of switching therapy in patients with high on-treatment platelet reactivity and genotype variation with high clopidogrel Dose versus prasugrel: the RESET GENE trial. Circ Cardiovasc Interv. 2012 Oct;5(5):698-704. doi: 10.1161/CIRCINTERVENTIONS.112.972463. Epub 2012 Oct 9.