Ignite Creation Date:
2024-05-05 @ 11:58 PM
Last Modification Date:
2024-10-26 @ 10:42 AM
Study NCT ID:
NCT01452139
Status:
COMPLETED
Last Update Posted:
2013-04-25
First Post:
2011-09-27
Brief Title:
Pharmacogenetic Approach to Anti-platelet Therapy for the Treatment of ST-segment Elevation Myocardial Infarction STEMI
Sponsor:
Ottawa Heart Institute Research Corporation
Organization:
Ottawa Heart Institute Research Corporation
Study Overview
Official Title:
ReAssessment of Anti-Platelet Therapy Using an InDividualized Strategy in Patients With ST-segment Elevation Myocardial Infarction
Status:
COMPLETED
Status Verified Date:
2013-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
RAPID STEMI
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 CYP2C192 17 and ABCB1 3435 CT alleles
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 CYP2C192 17 and ABCB1 3435 CT alleles
Presence of the CYP2C192 allele has been associated with a 15- 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 CYP2C1917 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 CYP2C192 17 and ABCB1 3435 CT 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 CYP2C192 17 and ABCB1 3435 CT alleles CYP2C192 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 CYP2C1917 allele will be prospectively evaluated during the treatment period
Presence of the CYP2C192 allele has been associated with a 15- 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 CYP2C1917 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 CYP2C192 17 and ABCB1 3435 CT 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 CYP2C192 17 and ABCB1 3435 CT alleles CYP2C192 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 CYP2C1917 allele will be prospectively evaluated during the treatment period
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None