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Pharmacogenetic Approach to Anti-platelet Therapy for the Treatment of ST-segment Elevation Myocardial Infarction (STEMI) (RAPID STEMI)

This study has been completed.
Sponsor:
Collaborator:
Spartan Bioscience Inc.
Information provided by (Responsible Party):
Derek So, University of Ottawa Heart Institute
ClinicalTrials.gov Identifier:
NCT01452139
First received: September 27, 2011
Last updated: April 23, 2013
Last verified: April 2013

September 27, 2011
April 23, 2013
September 2011
September 2012   (final data collection date for primary outcome measure)
The rates of high on-treatment platelet reactivity as measured by the VerifyNow P2Y12 assay (Accumetrics, San Diego, CA) in CYP2C19*2 and ABCB1 3435 TT carriers treated with prasugrel relative to clopidogrel. [ Time Frame: 1 month ] [ Designated as safety issue: No ]
High on-treatment platelet reactivity as measured by the VerifyNow P2Y12 assay with evidence based cutoffs.
Same as current
Complete list of historical versions of study NCT01452139 on ClinicalTrials.gov Archive Site
  • Composite of death from cardiovascular causes, non-fatal myocardial infarction, and re-hospitalization. [ Time Frame: 1 month ] [ Designated as safety issue: No ]
  • Bleeding risk [ Time Frame: 1 month ] [ Designated as safety issue: Yes ]
    Defined by TIMI major/minor
  • Concordance of point-of-care genetic screening with laboratory based genotyping methods [ Time Frame: 1 month ] [ Designated as safety issue: No ]
    Genotyping results from the Spartan RX device will be compared with the results of direct DNA sequencing.
  • Effect of the CYP2C19*17 allele on platelet inhibition. [ Time Frame: 1 month ] [ Designated as safety issue: No ]
    As measured by VerifyNow in P2Y12 Reaction Units (PRU) and percent platelet inhibition.
  • Effect of CYP2C19*17 allele on bleeding events [ Time Frame: 1 month ] [ Designated as safety issue: Yes ]
    Comparison of TIMI major & minor bleeding rates in carriers and non-carriers of the CYP2C19*17 allele.
  • Mean PRU and percent platelet inhibition in CYP2C19*2 and ABCB1 3435 TT carriers treated with prasugrel relative to clopidogrel [ Time Frame: 1 month ] [ Designated as safety issue: No ]
  • Between-group change in PRU and percent platelet inhibition in CYP2C19*2 and ABCB1 3435 TT carriers treated with prasugrel relative to clopidogrel. [ Time Frame: 1 month ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
Pharmacogenetic Approach to Anti-platelet Therapy for the Treatment of ST-segment Elevation Myocardial Infarction (STEMI)
ReAssessment of Anti-Platelet Therapy Using an InDividualized Strategy in Patients With ST-segment Elevation Myocardial Infarction

The objective of the RAPID STEMI study is to evaluate the feasibility, efficacy, and safety of a pharmacogenetic approach to anti-platelet therapy for the treatment of ST-segment elevation myocardial infarction (STEMI) patients following percutaneous coronary intervention (PCI) using point-of-care genetic testing for the CYP2C19*2, *17, and ABCB1 3435 C>T alleles.

Dual anti-platelet therapy following percutaneous coronary intervention (PCI) for the treatment of STEMI has traditionally consisted of aspirin and clopidogrel. Despite this treatment approach, a substantial portion of patients experience recurrent 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 high on-treatment platelet reactivity. Although multiple variables have been implicated in altered clopidogrel response, mounting evidence has suggested a crucial role for common genetic variants including: CYP2C19*2, *17, and ABCB1 3435 C>T alleles.

Presence of the CYP2C19*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 2 separate meta-analyses, 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. The ABCB1 3435 TT genotype has also been linked with increased adverse cardiovascular events in individuals treated with clopidogrel following PCI for an acute coronary syndrome. In contrast, the CYP2C19*17 gain-of-function allele appears to enhance the activity of clopidogrel and has been associated with reduced ischemic events but increased bleeding.

As a result of these findings, experts have begun to advocate for routine genotyping in the context of 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 point-of-care genetic testing for the CYP2C19*2, *17, and ABCB1 3435 C>T alleles that requires minimal training to perform carries the potential to overcome these obstacles and may facilitate the incorporation of pharmacogenetic strategies into routine clinical practice.

Patients receiving PCI in the context of STEMI will undergo point-of-care genetic testing for the CYP2C19*2, *17, and ABCB1 3435 C>T alleles. CYP2C19*2 carriers and individuals homozygous for the ABCB1 3435 T allele will subsequently be randomized to prasugrel 10mg daily for 1 month or clopidogrel 150mg daily for 1 week followed by 75mg daily. The remaining individuals without an at-risk genotype will receive standard therapy with clopidogrel. At the end of the 1 month period, efficacy of the treatment strategies will be evaluated using VerifyNow platelet function testing. The effect of the CYP2C19*17 allele will be prospectively evaluated during the treatment period.

Interventional
Phase 2
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
STEMI
  • Genetic: Point-of-Care Genetic Testing
    Point-of-Care Genetic Testing for Genetic Variants Linked to Adverse Outcomes with Clopidogrel (CYP2C19*2 & ABCB1 3435 TT)
    Other Name: Spartan RX
  • Drug: Prasugrel
    Treatment of STEMI patients carrying at least one high risk genetic variant with prasugrel 10mg daily.
    Other Name: Effient
  • Experimental: At-Risk Genetics Arm: Prasugrel
    Treatment of STEMI patients carrying at least 1 at-risk genetic variant with prasugrel 10mg daily for 1 month.
    Interventions:
    • Genetic: Point-of-Care Genetic Testing
    • Drug: Prasugrel
  • Active Comparator: At-Risk Genetics Arm: Clopidogrel
    Treatment of STEMI patients carrying at least 1 at-risk genetic variant with clopidogrel 150mg daily for 1 week followed by 75mg daily.
    Intervention: Genetic: Point-of-Care Genetic Testing
  • Active Comparator: Low Risk Genetics Arm: Clopidogrel
    Treatment of STEMI patients with no at-risk genetic variants with clopidogrel 75mg daily.
    Intervention: Genetic: Point-of-Care Genetic Testing

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
102
March 2013
September 2012   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Males and Females between the ages of 18 and 75 years
  • STEMI patients treated with percutaneous coronary intervention
  • Able to provide informed consent
  • Able to comply with assigned treatment strategy and attend 1 month follow-up visit

Exclusion Criteria:

  • Receiving anti-platelet therapy other than aspirin and clopidogrel
  • Receiving anti-coagulation with warfarin or dabigatran
  • History of stroke or transient ischemic attack
  • Platelet count < 100 000/μL
  • Known Bleeding Diathesis
  • Hematocrit <30% 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
 
NCT01452139
2010364-01H
Yes
Derek So, University of Ottawa Heart Institute
Ottawa Heart Institute Research Corporation
Spartan Bioscience Inc.
Principal Investigator: Derek Y F So, MD Ottawa Heart Institute Research Corporation
Study Director: Jason D Roberts, MD Ottawa Heart Institute Research Corporation
Ottawa Heart Institute Research Corporation
April 2013

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