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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Gennaro Sardella, University of Roma La Sapienza
ClinicalTrials.gov Identifier:
NCT01465828
First received: October 28, 2011
Last updated: March 24, 2012
Last verified: November 2011
  Purpose

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.


Condition Intervention Phase
Acute Coronary Syndrome
Drug: Clopidogrel
Drug: prasugrel
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by University of Roma La Sapienza:

Primary Outcome Measures:
  • antiplatelet effect of standard dose of prasugrel versus high dose clopidogrel in stable patients with HTPR [ Time Frame: 14-28 days ] [ Designated as safety issue: Yes ]
    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)


Secondary Outcome Measures:
  • Bleeding (major, minor, or minimal according to the TIMI study criteria) [ Time Frame: 14-28 days ] [ Designated as safety issue: Yes ]
    Bleeding (major, minor, or minimal according to the TIMI study criteria)

  • Major Adverse Cardiac Cerebrovascular Events [ Time Frame: 14-28 days ] [ Designated as safety issue: Yes ]
    cardiovascular death, myocardial infarction, and stroke


Enrollment: 30
Study Start Date: October 2011
Study Completion Date: January 2012
Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01465828

Locations
Italy
Dept.of Cardiovascular Sciences,Policlinico Umberto I
Roma, Italy, 00161
Dept.of Cardiovascular Sciences,Policlinico Umberto I
Rome, Italy, 00155
Sponsors and Collaborators
Gennaro Sardella
  More Information

No publications provided by University of Roma La Sapienza

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Gennaro Sardella, Associate Professor in Cardiology, University of Roma La Sapienza
ClinicalTrials.gov Identifier: NCT01465828     History of Changes
Other Study ID Numbers: RESET GENE
Study First Received: October 28, 2011
Last Updated: March 24, 2012
Health Authority: Italy: Ethics Committee

Keywords provided by University of Roma La Sapienza:
antiplatelet effect
prasugrel
clopidogrel
ACS

Additional relevant MeSH terms:
Acute Coronary Syndrome
Angina Pectoris
Cardiovascular Diseases
Chest Pain
Heart Diseases
Myocardial Ischemia
Pain
Signs and Symptoms
Vascular Diseases
Clopidogrel
Prasugrel
Ticlopidine
Cardiovascular Agents
Fibrin Modulating Agents
Fibrinolytic Agents
Hematologic Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Pharmacologic Actions
Physiological Effects of Drugs
Platelet Aggregation Inhibitors
Purinergic Agents
Purinergic Antagonists
Purinergic P2 Receptor Antagonists
Purinergic P2Y Receptor Antagonists
Therapeutic Uses

ClinicalTrials.gov processed this record on October 22, 2014