ReAssessment of Anti-Platelet Therapy Using an InDividualized Strategy Based on GENetic Evaluation
Information source: University of Ottawa Heart Institute
Information obtained from ClinicalTrials.gov on October 04, 2010
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Stable Coronary Artery Disease; Acute Coronary Syndrome; Percutaneous Coronary Intervention
Intervention: Point-of-care genetic screening with subsequent prasugrel administration to CYP2C19*2 carriers (Genetic)
Phase: Phase 2/Phase 3
Sponsored by: University of Ottawa Heart Institute
Official(s) and/or principal investigator(s):
Derek Y.F. So, MD, Principal Investigator, Affiliation: University of Ottawa Heart Institute
Jason D. Roberts, MD, Study Director, Affiliation: University of Ottawa Heart Institute
Derek Y. F. So, MD, Phone: (613)761-5387, Email: firstname.lastname@example.org
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.
Official title: ReAssessment of Anti-Platelet Therapy Using an InDividualized Strategy Based on GENetic Evaluation (The RAPID GENE Study)
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Clopidogrel response status as measured by the VerifyNow P2Y12 assay (Accumetrics, San Diego, CA) in CYP2C19*2 carriers.
Concordance of point-of-care genetic screening with laboratory based genotyping methods
Composite of death from cardiovascular causes, non-fatal myocardial infarction, and re-hospitalization
Incidence of stent thrombosis
Feasibility of point-of-care genotyping in randomized setting
Influence of Alternate CYP2C19 variants on outcomes
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
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.
Minimum age: 18 Years.
Maximum age: 75 Years.
- 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
- 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
Locations and Contacts
Derek Y. F. So, MD, Phone: (613)761-5387, Email: email@example.com
University of Ottawa Heart Institute, Ottawa, Ontario K1Y 4W7, Canada; Recruiting
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Sibbing D, Stegherr J, Latz W, Koch W, Mehilli J, Dörrler K, Morath T, Schömig A, Kastrati A, von Beckerath N. Cytochrome P450 2C19 loss-of-function polymorphism and stent thrombosis following percutaneous coronary intervention. Eur Heart J. 2009 Apr;30(8):916-22. Epub 2009 Feb 4.
Starting date: August 2010
Last updated: August 23, 2010