Ignite Creation Date:
2024-05-05 @ 5:21 PM
Last Modification Date:
2024-10-26 @ 9:30 AM
Study NCT ID:
NCT00433784
Status:
COMPLETED
Last Update Posted:
2012-08-21
First Post:
2007-02-08
Brief Title:
H2 Haplotype and CYP3As Polymorphisms and the Antiplatelet Response to Clopidogrel
Sponsor:
Hopital du Sacre-Coeur de Montreal
Organization:
Hopital du Sacre-Coeur de Montreal
Study Overview
Official Title:
Evaluation of the Effect of the H2 Haplotype and CYP3As Polymorphisms on the Antiplatelet Response to Clopidogrel Given Before Elective Percutaneous Coronary Intervention
Status:
COMPLETED
Status Verified Date:
2008-06
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:
None
Brief Summary:
The purpose of this study was to assess whether interpatient variability in the platelet response to clopidogrel is partly due to polymorphisms of the hepatic cytochrome P450 CYP4503A and of the clopidogrel-P2Y12 receptor genes
Detailed Description:
Clopidogrel owes its antiplatelet effect to irreversible inhibition of the purinergic platelet receptor P2Y12 It is estimated that approximately 4-30 of patients treated with conventional doses of clopidogrel do not display adequate platelet response Moreover patients with low response to clopidogrel may be at higher risk for atherothrombotic events Clopidogrel being a prodrug requires oxidation by the hepatic cytochrome P450 CYP4503A to generate an active metaboliteThe level of CYP3A4 activity has been shown to correlate with the inhibitory effect of clopidogrel on platelet aggregation in healthy volunteers However CYP3As expression and activity vary among individuals It is estimated that most of this variability is caused by individual genetic makeupPolymorphisms of the P2Y12 receptor may also play a role in the variability in clopidogrel response The P2Y12-H2 haplotype was associated with higher maximal platelet aggregation in response to adenosine diphosphate ADP as compared to the P2Y12-H1 haplotype probably due to an increase in the number of receptors on the platelet surface It has also been suggested that carriers of the H2 haplotype might be at higher risk of developing peripheral artery disease
Comparisons Presence of CYP3A5 polymorphism and of the H2 haplotype compared to absence of these polymorphisms on the antiplatelet response to clopidogrel across a wide range of clopidogrel dosing regimens in patients with suspected or demonstrated coronary artery disease CAD scheduled to undergo elective percutaneous coronary intervention PCI
Platelet aggregation was measured by optical aggregometry with ADP 20 μmolL as the agonist in patients before clopidogrel initiation and at the time of diagnostic coronary angiography Genotyping was performed by standard polymerase chain reaction PCR method to identify expressors of CYP3A5 and P2Y12 H2 haplotype carriers
Comparisons Presence of CYP3A5 polymorphism and of the H2 haplotype compared to absence of these polymorphisms on the antiplatelet response to clopidogrel across a wide range of clopidogrel dosing regimens in patients with suspected or demonstrated coronary artery disease CAD scheduled to undergo elective percutaneous coronary intervention PCI
Platelet aggregation was measured by optical aggregometry with ADP 20 μmolL as the agonist in patients before clopidogrel initiation and at the time of diagnostic coronary angiography Genotyping was performed by standard polymerase chain reaction PCR method to identify expressors of CYP3A5 and P2Y12 H2 haplotype carriers
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