Clopidogrel Pharmacogenomics Project
Recruitment status was Recruiting
Loss-of-function mutation of the gene encoding the CYP450 2C19 enzyme has emerged as a likely determinant of resistance to clopidogrel therapy. The primary hypothesis of the proposed research is that among patients with confirmed loss-of-function alleles of the CYP2C19 gene, increasing the maintenance clopidogrel dose from 75 to 150 mg will result in significant reduction in the rate of measured clopidogrel resistance defined by multiple measures of platelet function
|Study Design:||Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Diagnostic
|Official Title:||Clopidogrel Pharmacogenomics Project|
- Clopidogrel Pharmacogenomics Project [ Time Frame: Approximately 90 days ] [ Designated as safety issue: Yes ]Among patients with loss-of-function alleles for the enzyme encoding CYP450 2C19, increasing the maintenance clopidogrel dose from 75 to 150 mg will result in a significant decrease in the proportion of patients with resistance to clopidogrel, defined as more than 235 Platelet Reactivity Units (PRUs) measured by the VerfifyNow point of care P2Y12 assay.
- Clopidogrel Pharmacogenomics Project [ Time Frame: Approximately 90 days ] [ Designated as safety issue: Yes ]
- Loss-of-function alleles for the CYP450 2C19 gene are equally prevalent among Caucasian and African-American populations, and correlate similarly with measures of platelet function.
- Using light transmission aggregometry with ADP agonist (BioData) as the "gold standard" test, platelet function measured by VerifyNow P2Y12 point of care assay will show significant correlation when measured as a continuous variable. The EQELS assay will predict clopidogrel resistance with similar sensitivity and specifity compared to the VerifyNow assay.
|Study Start Date:||March 2010|
|Estimated Study Completion Date:||May 2011|
|Estimated Primary Completion Date:||April 2011 (Final data collection date for primary outcome measure)|
|Active Comparator: 75 mg clopidogrel||
Drug: clopidogrel 75 mg
75 mg once daily
Other Name: Plavix
|Active Comparator: 150 mg clopidogrel||
Drug: Clopidogrel 150 mg
clopidogrel 150 mg
Other Name: Plavix
The first phase of the clinical trial will involve subject recruitment and informed consent for genetic testing. Because the target population is patients with stable coronary artery disease, patients will be recruited from the outpatient setting during clinic visits or at the time of outpatient cardiac catheterization. It is expected that all potential candidates will be initially screened for eligibility by their treating cardiologist. If a patient agrees to undergo formal screening, they will be approached by a member of the research team and receive a written summary of the clinical trial protocol that will be reviewed with the trial personnel. The initial informed consent will allow the patient to undergo genetic testing and baseline VerifyNow assay, and will also give the trial personnel permission to contact the patient by phone if they are found to be eligible for the interventional phase of the trial. The goal for enrollment in the genetic testing portion of this clinical trial is 200 patients.
If the genetic testing results confirm that the patient is a candidate for the interventional study, they will be contacted and asked to make an outpatient appointment to initiate the interventional study protocol. The therapeutic portion of this study will be a randomized, unblinded cross-over comparison of two clopidogrel dosing strategies. It is anticipated that all eligible patients will have continued their previous chronic clopidogrel therapy with standard dosing of 75 mg/day. Because all patients will be receiving chronic clopidogrel at the initiation of the intervention protocol, steady state levels should be present in all patients. Dose dependent inhibition of platelet aggregation can be seen two hours after a single oral dose of clopidogrel. Repeated doses of 75mg daily produce steady state inhibition between day 3 and day 7 of administration.
Patients who agree to participate in the therapeutic protocol, and who meet the eligibility criteria, will be randomized to an initial dosing strategy of 75 or 150 mg daily for a minimum of 30 days. At day 30 (+/- 5 days), patients will return for repeat platelet function testing. In a randomly selected subset of 15 patients, blood will be tested for the active metabolite of clopidogrel. At that time, there will be a crossover with those patients receiving 75 mg qD increased to 150 mg qD and those receiving 150 mg qD decreased to 75 mg qD. At day 60 (+/- 5 days), participants will again return for comprehensive platelet function testing and a second randomly selected group of patients will undergo testing for clopidogrel metabolites. Chronic clopidogrel dosing will be reduced to 75mg in all participants. Please see the attached schedule of events for a summary of the trial schedule.
|Contact: Jaya Dharmavaram, M.Demail@example.com|
|Contact: Joseph S Rossi, M.Dfirstname.lastname@example.org|
|United States, North Carolina|
|UNC Chapel Hill||Recruiting|
|Chapel HIll, North Carolina, United States, 27599|
|Contact: Jaya Dharmavaram, M.D 919-843-5215 email@example.com|
|Contact: Joseph S Rossi, M.D 919-843-9935 firstname.lastname@example.org|
|Principal Investigator: Joseph S Rossi, M.D|
|Principal Investigator:||Joseph Rossi, MD||University of North Carolina, Chapel Hill|