Ignite Creation Date:
2025-12-24 @ 4:11 PM
Ignite Modification Date:
2026-01-02 @ 9:20 AM
Study NCT ID:
NCT00822666
Status:
COMPLETED
Last Update Posted:
2012-12-11
First Post:
2009-01-13
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Clopidogrel and Response Variability Investigation Study 2
Sponsor:
Assistance Publique - Hôpitaux de Paris
Organization:
Study Overview
Official Title:
Effect of the Genetic Variant 2C19*2 on Clopidogrel Biological Response in Patients With Premature Coronary Artery Disease
Status:
COMPLETED
Status Verified Date:
2009-01
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:
CLOVIS2
Brief Summary:
To evaluate the role of the genetic variant 2C19\*2 on the pharmacodynamic response as assessed by optical aggregometry and on the pharmacokinetic response as assessed by measuring active metabolites following an oral administration of a loading dose of 300/900mg of clopidogrel in patients with established coronary artery disease.
Detailed Description:
Rationale : Clopidogrel is a specific and irreversible of the P2Y12 platelet receptor leading to an inhibition of platelet aggregation. Clopidogrel is a prodrug that must be converted into an active metabolite that selectively and irreversibly binds to the P2Y12 platelet membrane receptor. As a consequence, a loading dose of 300 mg is necessary in percutaneous coronary intervention and in acute coronary syndrome, situations which require a rapid inhibition of platelet aggregation due to the high thrombotic risk.
High platelet reactivity on clopidogrel may be due to various reasons including polymorphism in the gene encoding the cytochrome P-450 2C19 enzyme (CYP2C19) which has been shown to contribute to the variability of platelet response to clopidogrel. CYP2C19 is a key enzyme in this activation process and our group was the first to describe an association between the presence of the loss of function CYP2C19 681G\>A polymorphism (also called \*2) with lower clopidogrel responsiveness in healthy subjects.
Poor responsiveness to clopidogrel has become a major concern given acute recurrent events following stent placement.
Objective : To evaluate the role of the genetic variant 2C19\*2 on the pharmacodynamic response as assessed by optical aggregometry and on the pharmacokinetic response as assessed by measuring active metabolites following an oral administration of a loading dose of 300/900mg of clopidogrel in patients with established coronary artery disease.
Target population :Patients of less than 45 years of age and who survived a MI and enrolled in the AFIJI multicenter registry (Appraisal of risk Factors in young Ischemic patients Justifying aggressive Intervention).
Primary end-point :Comparison of inhibition of the intensity of residual platelet aggregation (IRPA) measured 6 minutes after induction by 20 μmol/L following 300mg or 900 mg of clopidogrel with respect to the presence of the genetic variant CYP2C19\*2
1. Maximum platelet aggregation instead of IRPA
2. RPA with 5µM and 50 µM of ADP
3. Measure of clopidogrel and its active metabolites (carboxylated and thiol) at different time points following the loading dose (H0, H1, H2 et H6) with respect to the presence of the genetic variant CYP2C19\*2
4. Relationship between active metabolites concentration and IRPA
5. Relationship between active metabolites and dose of clopidogrel
6. Comparison of 300mg vs 900mg on IRPA in the whole population irrespective of the genetic variant
Statistical analysis :Comparison of IRPA with respect to the presence of the genetic variant 2C19\*2 by anova Area under the curve of the production of active metabolites with respect to the presence of the genetic variant 2C19\*2 Agenda :November 2008 (inclusion of first patient) to december 2009 (analysis of the data)
High platelet reactivity on clopidogrel may be due to various reasons including polymorphism in the gene encoding the cytochrome P-450 2C19 enzyme (CYP2C19) which has been shown to contribute to the variability of platelet response to clopidogrel. CYP2C19 is a key enzyme in this activation process and our group was the first to describe an association between the presence of the loss of function CYP2C19 681G\>A polymorphism (also called \*2) with lower clopidogrel responsiveness in healthy subjects.
Poor responsiveness to clopidogrel has become a major concern given acute recurrent events following stent placement.
Objective : To evaluate the role of the genetic variant 2C19\*2 on the pharmacodynamic response as assessed by optical aggregometry and on the pharmacokinetic response as assessed by measuring active metabolites following an oral administration of a loading dose of 300/900mg of clopidogrel in patients with established coronary artery disease.
Target population :Patients of less than 45 years of age and who survived a MI and enrolled in the AFIJI multicenter registry (Appraisal of risk Factors in young Ischemic patients Justifying aggressive Intervention).
Primary end-point :Comparison of inhibition of the intensity of residual platelet aggregation (IRPA) measured 6 minutes after induction by 20 μmol/L following 300mg or 900 mg of clopidogrel with respect to the presence of the genetic variant CYP2C19\*2
1. Maximum platelet aggregation instead of IRPA
2. RPA with 5µM and 50 µM of ADP
3. Measure of clopidogrel and its active metabolites (carboxylated and thiol) at different time points following the loading dose (H0, H1, H2 et H6) with respect to the presence of the genetic variant CYP2C19\*2
4. Relationship between active metabolites concentration and IRPA
5. Relationship between active metabolites and dose of clopidogrel
6. Comparison of 300mg vs 900mg on IRPA in the whole population irrespective of the genetic variant
Statistical analysis :Comparison of IRPA with respect to the presence of the genetic variant 2C19\*2 by anova Area under the curve of the production of active metabolites with respect to the presence of the genetic variant 2C19\*2 Agenda :November 2008 (inclusion of first patient) to december 2009 (analysis of the data)
Study Oversight
Has Oversight DMC:
False
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?: