ReAssessment of Anti-Platelet Therapy Using an InDividualized Strategy Based on GENetic Evaluation (RAPID GENE)
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|ClinicalTrials.gov Identifier: NCT01184300|
Recruitment Status : Completed
First Posted : August 18, 2010
Last Update Posted : November 11, 2011
|Condition or disease||Intervention/treatment||Phase|
|Stable Coronary Artery Disease Acute Coronary Syndrome Percutaneous Coronary Intervention||Genetic: Point-of-care genetic screening with subsequent prasugrel administration to CYP2C19*2 carriers||Phase 2 Phase 3|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||200 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||ReAssessment of Anti-Platelet Therapy Using an InDividualized Strategy Based on GENetic Evaluation (The RAPID GENE Study)|
|Study Start Date :||August 2010|
|Actual Primary Completion Date :||July 2011|
|Actual Study Completion Date :||July 2011|
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.
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)
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.
- Clopidogrel response status as measured by the VerifyNow P2Y12 assay (Accumetrics, San Diego, CA) in CYP2C19*2 carriers. [ Time Frame: 1 week ]Response status defined in P2Y12 Reaction Units (PRU) and percent platelet inhibition.
- Concordance of point-of-care genetic screening with laboratory based genotyping methods [ Time Frame: 1 week ]
- Composite of death from cardiovascular causes, non-fatal myocardial infarction, and re-hospitalization [ Time Frame: 1 week and 6 months ]
- Bleeding risk [ Time Frame: 1 week and 6 months ]Defined by TIMI major/minor
- Incidence of stent thrombosis [ Time Frame: 1 week and 6 months ]ARC definitions
- Feasibility of point-of-care genotyping in randomized setting [ Time Frame: 1 week ]
- Influence of Alternate CYP2C19 variants on outcomes [ Time Frame: 1 week and 6 months ]CYP2C19 - functional polymorphisms
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01184300
|University of Ottawa Heart Institute|
|Ottawa, Ontario, Canada, K1Y 4W7|
|Principal Investigator:||Derek Y.F. So, MD||Ottawa Heart Institute Research Corporation|
|Study Director:||Jason D. Roberts, MD||Ottawa Heart Institute Research Corporation|