Pharmacogenetic Approach to Anti-platelet Therapy for the Treatment of ST-segment Elevation Myocardial Infarction (STEMI) (RAPID STEMI)
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| First Received Date ICMJE | September 27, 2011 | ||||||||
| Last Updated Date | April 23, 2013 | ||||||||
| Start Date ICMJE | September 2011 | ||||||||
| Primary Completion Date | September 2012 (final data collection date for primary outcome measure) | ||||||||
| Current Primary Outcome Measures ICMJE |
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. |
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| Original Primary Outcome Measures ICMJE | Same as current | ||||||||
| Change History | Complete list of historical versions of study NCT01452139 on ClinicalTrials.gov Archive Site | ||||||||
| Current Secondary Outcome Measures ICMJE |
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| Original Secondary Outcome Measures ICMJE | Same as current | ||||||||
| Current Other Outcome Measures ICMJE | Not Provided | ||||||||
| Original Other Outcome Measures ICMJE | Not Provided | ||||||||
| Descriptive Information | |||||||||
| Brief Title ICMJE | Pharmacogenetic Approach to Anti-platelet Therapy for the Treatment of ST-segment Elevation Myocardial Infarction (STEMI) | ||||||||
| Official Title ICMJE | ReAssessment of Anti-Platelet Therapy Using an InDividualized Strategy in Patients With ST-segment Elevation Myocardial Infarction | ||||||||
| Brief Summary | 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. |
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| Detailed Description | 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. |
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| Study Type ICMJE | Interventional | ||||||||
| Study Phase | Phase 2 Phase 3 |
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| Study Design ICMJE | Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Single Blind (Outcomes Assessor) Primary Purpose: Treatment |
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| Condition ICMJE | STEMI | ||||||||
| Intervention ICMJE |
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| Publications * |
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* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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| Recruitment Information | |||||||||
| Recruitment Status ICMJE | Completed | ||||||||
| Enrollment ICMJE | 102 | ||||||||
| Completion Date | March 2013 | ||||||||
| Primary Completion Date | September 2012 (final data collection date for primary outcome measure) | ||||||||
| Eligibility Criteria ICMJE | Inclusion Criteria:
Exclusion Criteria:
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| Gender | Both | ||||||||
| Ages | 18 Years to 75 Years | ||||||||
| Accepts Healthy Volunteers | No | ||||||||
| Contacts ICMJE | Contact information is only displayed when the study is recruiting subjects | ||||||||
| Location Countries ICMJE | Canada | ||||||||
| Administrative Information | |||||||||
| NCT Number ICMJE | NCT01452139 | ||||||||
| Other Study ID Numbers ICMJE | 2010364-01H | ||||||||
| Has Data Monitoring Committee | Yes | ||||||||
| Responsible Party | Derek So, University of Ottawa Heart Institute | ||||||||
| Study Sponsor ICMJE | University of Ottawa Heart Institute | ||||||||
| Collaborators ICMJE | Spartan Bioscience Inc. | ||||||||
| Investigators ICMJE |
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| Information Provided By | University of Ottawa Heart Institute | ||||||||
| Verification Date | April 2013 | ||||||||
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ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |
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