Therapy With High Clopidogrel Dose or Prasugrel Standard Dose Reduces the Platelet Reactivity in Patients With Genotype Variation RESET GENE Trial (RESET GENE)

PhaRmacodynamic Effects of Switching thErapy in paTients With High on Treatment Platelet Reactivity and Genotype Variation: High Clopidogrel Dose Versus Prasugrel RESET GENE Trial

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.

Study Overview

• Status: Completed
• Conditions: Acute Coronary Syndrome
• Intervention / Treatment: Drug: Clopidogrel; Drug: prasugrel

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 3

Contacts and Locations

Study Locations

• Italy
  • Roma, Italy, 00161
    • Dept.of Cardiovascular Sciences,Policlinico Umberto I
  • Rome, Italy, 00155
    • Dept.of Cardiovascular Sciences,Policlinico Umberto I

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: high clopidogrel dose; Patients will be randomized to this arm to receive before high clopidogrel dose and after crossover they will receive standard dose of prasugrel	Drug: Clopidogrel; Patient will be randomized to this intervention will receive in the first time the high clopidogrel dose and after 14 days we will change their therapy with standard dose of prasugrel (crossover).; Drug: prasugrel; Patient will be randomized to this intervention will receive in the first time the standard dose of prasugrel and after 14 days we will change their therapy with high dose of clopidogrel (crossover).
No Intervention: prasugrel standard dose; Patients will be randomized to this arm to receive before standard dose of prasugrel and after crossover they will receive high clopidogrel dose.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
antiplatelet effect of standard dose of prasugrel versus high dose clopidogrel in stable patients with HTPR	The primary aim will be to investigate the antiplatelet effect of standard dose of prasugrel versus high dose clopidogrel in stable patients with HTPR while receiving chronic clopidogrel treatment at the end of the 2 study periods (switching, crossover and post-crossover)	14-28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bleeding (major, minor, or minimal according to the TIMI study criteria)	Bleeding (major, minor, or minimal according to the TIMI study criteria)	14-28 days
Major Adverse Cardiac Cerebrovascular Events	cardiovascular death, myocardial infarction, and stroke	14-28 days

Collaborators and Investigators

• Sponsor: Gennaro Sardella

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: October 1, 2011
• Primary Completion (Actual): January 1, 2012
• Study Completion (Actual): January 1, 2012

Study Registration Dates

• First Submitted: October 28, 2011
• First Submitted That Met QC Criteria: November 4, 2011
• First Posted (Estimate): November 6, 2011

Study Record Updates

• Last Update Posted (Estimate): March 27, 2012
• Last Update Submitted That Met QC Criteria: March 24, 2012
• Last Verified: November 1, 2011

More Information

Terms related to this study

• Keywords: prasugrel; clopidogrel; ACS; antiplatelet effect
• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Acute Coronary Syndrome; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Clopidogrel; Prasugrel Hydrochloride
• Other Study ID Numbers: RESET GENE