ReAssessment of Anti-Platelet Therapy Using an InDividualized Strategy Based on GENetic Evaluation

NCT ID: NCT01184300

Last Updated: 2011-11-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 200 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-08-31
• Study Completion Date: 2011-07-31

Brief Summary

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.

Detailed Description

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.

Conditions

Stable Coronary Artery Disease; Acute Coronary Syndrome; Percutaneous Coronary Intervention

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Point-of-care genetic screening with subsequent prasugrel administration to CYP2C19*2 carriers

Intervention Type: GENETIC

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.

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.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

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.

Intervention Type: GENETIC

Other Intervention Names

Prasugrel (Effient)

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Spartan Bioscience Inc.

INDUSTRY

Sponsor Role: collaborator

Ottawa Heart Institute Research Corporation

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Derek Y.F. So, MD

Role: PRINCIPAL_INVESTIGATOR

Ottawa Heart Institute Research Corporation

Jason D. Roberts, MD

Role: STUDY_DIRECTOR

Ottawa Heart Institute Research Corporation

Locations

University of Ottawa Heart Institute

Ottawa, Ontario, Canada

Countries

Canada

References

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Reference Type: BACKGROUND

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Reference Type: BACKGROUND

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Reference Type: BACKGROUND

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Reference Type: DERIVED

PMID: 22464343 (View on PubMed)

Other Identifiers

HC-9427-U0143-43C

Identifier Type: -

Identifier Source: org_study_id