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

NCT01465828 | Completed Phase 3 DMC

• 1 other identifier: RESET GENE
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 2

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.

Conditions

Acute Coronary Syndrome

Keywords

antiplatelet effect; prasugrel; clopidogrel; ACS

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Bleeding (major, minor, or minimal according to the TIMI study criteria)

  14-28 days

• Major Adverse Cardiac Cerebrovascular Events

  14-28 days

Study Arms (2)

high clopidogrel dose

ACTIVE COMPARATOR

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; Drug: prasugrel

prasugrel standard dose

NO INTERVENTION

Patients will be randomized to this arm to receive before standard dose of prasugrel and after crossover they will receive high clopidogrel dose.

Interventions

Clopidogrel DRUG

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).

high clopidogrel dose

prasugrel DRUG

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).

high clopidogrel dose

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• patients underwent to PCI
• lopidogrel resistance after Platelet reactivity blood test

You may not qualify if:

• 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.

Sponsors & Collaborators

• Gennaro Sardella: lead

Study Sites (2)

Dept.of Cardiovascular Sciences,Policlinico Umberto I

Roma, Roma, 00161, Italy

Location

Dept.of Cardiovascular Sciences,Policlinico Umberto I

Rome, Rome, 00155, Italy

Location

Related Publications (1)

• 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.

  PMID: 23048056 DERIVED

MeSH Terms

Conditions

Acute Coronary Syndrome

Interventions

Clopidogrel; Prasugrel Hydrochloride

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Ticlopidine; Thienopyridines; Thiophenes; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Piperazines

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor in Cardiology

Study Record Dates

• First Submitted: October 28, 2011
• First Posted: November 7, 2011
• Study Start: October 1, 2011
• Primary Completion: January 1, 2012
• Study Completion: January 1, 2012
• Last Updated: March 27, 2012

Record last verified: 2011-11

Locations

IT (2)