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
  Purpose

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.


Condition Intervention 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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: ReAssessment of Anti-Platelet Therapy Using an InDividualized Strategy Based on GENetic Evaluation (The RAPID GENE Study)

Resource links provided by NLM:


Further study details as provided by University of Ottawa Heart Institute:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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


Enrollment: 200
Study Start Date: August 2010
Study Completion Date: July 2011
Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01184300

Locations
Canada, Ontario
University of Ottawa Heart Institute
Ottawa, Ontario, Canada, K1Y 4W7
Sponsors and Collaborators
University of Ottawa Heart Institute
Spartan Bioscience Inc.
Investigators
Principal Investigator: Derek Y.F. So, MD University of Ottawa Heart Institute
Study Director: Jason D. Roberts, MD University of Ottawa Heart Institute
  More Information

Publications:

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: University of Ottawa Heart Institute
ClinicalTrials.gov Identifier: NCT01184300     History of Changes
Other Study ID Numbers: HC-9427-U0143-43C
Study First Received: August 17, 2010
Last Updated: November 10, 2011
Health Authority: Canada: Health Canada

Keywords provided by University of Ottawa Heart Institute:
CYP2C19*2
Pharmacogenomics
Clopidogrel
Prasugrel
Percutaneous Coronary Intervention

Additional relevant MeSH terms:
Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Acute Coronary Syndrome
Heart Diseases
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Angina Pectoris
Chest Pain
Pain
Signs and Symptoms
Clopidogrel
Prasugrel
Platelet Aggregation Inhibitors
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Purinergic P2Y Receptor Antagonists
Purinergic P2 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 22, 2014