ReAssessment of Anti-Platelet Therapy Using an InDividualized Strategy Based on GENetic Evaluation (RAPID GENE)

This study has been completed.
Sponsor:
Collaborator:
Spartan Bioscience Inc.
Information provided by (Responsible Party):
University of Ottawa Heart Institute
ClinicalTrials.gov Identifier:
NCT01184300
First received: August 17, 2010
Last updated: November 10, 2011
Last verified: November 2011

August 17, 2010
November 10, 2011
August 2010
July 2011   (final data collection date for primary outcome measure)
Clopidogrel response status as measured by the VerifyNow P2Y12 assay (Accumetrics, San Diego, CA) in CYP2C19*2 carriers. [ Time Frame: 1 week ] [ Designated as safety issue: No ]
Response status defined in P2Y12 Reaction Units (PRU) and percent platelet inhibition.
Same as current
Complete list of historical versions of study NCT01184300 on ClinicalTrials.gov Archive Site
  • Concordance of point-of-care genetic screening with laboratory based genotyping methods [ Time Frame: 1 week ] [ Designated as safety issue: No ]
  • Composite of death from cardiovascular causes, non-fatal myocardial infarction, and re-hospitalization [ Time Frame: 1 week and 6 months ] [ Designated as safety issue: No ]
  • Bleeding risk [ Time Frame: 1 week and 6 months ] [ Designated as safety issue: Yes ]
    Defined by TIMI major/minor
  • Incidence of stent thrombosis [ Time Frame: 1 week and 6 months ] [ Designated as safety issue: Yes ]
    ARC definitions
  • Feasibility of point-of-care genotyping in randomized setting [ Time Frame: 1 week ] [ Designated as safety issue: No ]
  • Influence of Alternate CYP2C19 variants on outcomes [ Time Frame: 1 week and 6 months ] [ Designated as safety issue: No ]
    CYP2C19 - functional polymorphisms
Same as current
Not Provided
Not Provided
 
ReAssessment of Anti-Platelet Therapy Using an InDividualized Strategy Based on GENetic Evaluation
ReAssessment of Anti-Platelet Therapy Using an InDividualized Strategy Based on GENetic Evaluation (The RAPID GENE Study)

The objective of the RAPID GENE study is to evaluate the feasibility, efficacy and safety of a pharmacogenomic approach to anti-platelet therapy following coronary artery stenting using a CYP2C19*2 point-of-care genetic test.

Effective medical treatment following acute coronary syndromes and percutaneous coronary intervention (PCI) consists of dual anti-platelet therapy with aspirin and clopidogrel. Despite this treatment approach, a substantial portion of patients continue to experience an increased rate of subsequent adverse cardiovascular events including death, myocardial infarction, and stent thrombosis. This persistent vulnerability has been associated with inadequate platelet inhibition in response to clopidogrel administration, a phenomenon referred to as clopidogrel resistance. Although multiple variables have been implicated in clopidogrel resistance, mounting evidence suggests a crucial role for the loss-of-function CYP2C19*2 genetic variant. Presence of the *2 allele has been associated with a 1.5- to 6-fold increased risk of cardiovascular death, myocardial infarction, and stent thrombosis following PCI in patients treated with clopidogrel. These findings, recently bolstered by a meta-analysis, led the American Food and Drug Administration to issue a boxed warning for clopidogrel stating that poor metabolizers may not receive the full benefit of the drug. Consequently, experts have begun to advocate for routine genotyping in the context of dual anti-platelet therapy following PCI. A personalized approach to dual anti-platelet therapy following PCI is feasible given the presence of treatment alternatives such as prasugrel that are capable of overcoming clopidogrel resistance. Selective administration of prasugrel to patients at increased risk of clopidogrel resistance has the potential to successfully minimize adverse ischemic events, while simultaneously minimizing associated bleeding events and health care costs. A prospective pharmacogenomic approach to anti-platelet therapy has been previously hampered by limited access and the time-delay associated with genetic testing. The development of a point-of-care CYP2C19*2 genetic test that requires minimal training to operate carries the potential to overcome these obstacles and may facilitate the incorporation of pharmacogenomic strategies into routine clinical practice.

Patients receiving percutaneous coronary intervention in the context of non-ST elevation acute coronary syndromes and stable coronary artery disease will be randomized to either a rapid genotyping strategy or standard therapy. Patients in the Rapid Genotyping arm will be screened for the presence of the CYP2C19*2 allele using a point-of-care genetic test. Carriers of the *2 allele will receive prasugrel 10 mg daily for 1 week. Non-*2 carriers in the Rapid Genotyping arm and all patients in the Standard Therapy arm will receive clopidogrel 75 mg daily. At the end of the 1 week period, efficacy of the treatment strategies will be evaluated using VerifyNow platelet function testing.

Interventional
Phase 2
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Stable Coronary Artery Disease
  • Acute Coronary Syndrome
  • Percutaneous Coronary Intervention
Genetic: Point-of-care genetic screening with subsequent prasugrel administration to CYP2C19*2 carriers
Patients found to carry the CYP2C19*2 allele will receive prasugrel 10 mg daily for 1 week. Non-carriers will receive clopidogrel 75 mg daily.
Other Name: Prasugrel (Effient)
  • Experimental: Rapid Genotyping
    Patients randomized to the Rapid Genotyping arm will have their CYP2C19*2 carrier status determined at the time of percutaneous coronary intervention with subsequent alteration in anti-platelet therapy for *2 carriers.
    Intervention: Genetic: Point-of-care genetic screening with subsequent prasugrel administration to CYP2C19*2 carriers
  • No Intervention: Standard Therapy
    Patients randomized to the Standard Therapy arm will not undergo genotyping at the time of percutaneous coronary intervention. All patients will receive clopidogrel 75 mg daily for 1 week. At the end of the 1 week period, their CYP2C19*2 carrier status will be verified.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
200
July 2011
July 2011   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Males and Females between the ages of 18 and 75 years
  • Patients undergoing percutaneous coronary intervention in the context of a non-ST-elevation acute coronary syndrome or stable coronary artery disease
  • Able to provide informed consent
  • Able to comply with assigned treatment strategy and attend 1 week follow-up visit

Exclusion Criteria:

  • Receiving anti-platelet therapy other than aspirin and clopidogrel
  • Receiving anti-coagulation with warfarin
  • History of stroke or transient ischemic attack
  • Platelet count < 100 000/μL
  • Known Bleeding Diathesis
  • Hematocrit <32% or >52%
  • Severe Liver Dysfunction
  • Renal Insufficiency (Creatinine Clearance < 30ml/min)
  • Pregnant females
Both
18 Years to 75 Years
No
Contact information is only displayed when the study is recruiting subjects
Canada
 
NCT01184300
HC-9427-U0143-43C
No
University of Ottawa Heart Institute
University of Ottawa Heart Institute
Spartan Bioscience Inc.
Principal Investigator: Derek Y.F. So, MD University of Ottawa Heart Institute
Study Director: Jason D. Roberts, MD University of Ottawa Heart Institute
University of Ottawa Heart Institute
November 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP