Clopidogrel Pharmacogenomics Project

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Joseph S. Rossi M.D., University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier:
NCT01097343
First received: March 30, 2010
Last updated: February 26, 2014
Last verified: February 2014
  Purpose

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


Condition Intervention Phase
Disease Susceptibility
Drug: clopidogrel 75 mg
Drug: Clopidogrel 150 mg
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: Clopidogrel Pharmacogenomics Project

Resource links provided by NLM:


Further study details as provided by University of North Carolina, Chapel Hill:

Primary Outcome Measures:
  • Clopidogrel Resistance, Defined by P2Y12 Reaction Units (PRU)Value >230 [ Time Frame: Approximately 90 days ] [ Designated as safety issue: No ]
    P2Y12 Reaction Units are measured using the VerifyNow P2Y12 assay. Percent of patients with clopidogrel resistance defined by PRU value will be compared among low and high dose clopidogrel groups after 30 days of therapy.


Enrollment: 50
Study Start Date: March 2010
Study Completion Date: May 2011
Primary Completion Date: April 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:• Currently taking clopidogrel 75 mg/day and aspirin (minimum 81 mg/day) with an indication for chronic dual antiplatelet therapy (>90 days)

  • No evidence of acute coronary syndrome within 30 days of enrollment, defined by elevation of Troponin I above the upper limit of normal
  • Coronary atherosclerosis documented on previous coronary angiogram
  • No known contraindications to combination therapy with aspirin and clopidogrel
  • Prognosis for survival greater than one year based on physician's assessment
  • Able to attend all scheduled visits.
  • Access to phone
  • Subject is a female with a negative urine or serum pregnancy test or post-menopausal for at least 1 year prior to randomization. Females of childbearing potential must be practicing adequate birth control to be eligible. It is the Investigator's responsibility for determining whether the Subject has adequate birth control for study participation

Exclusion Criteria:• Recent acute coronary syndrome (<30 days)

  • Recent hospitalization or physician visit for bleeding disorder(<90 days) or history of chronic blood loss
  • Recent blood transfusion (<90 days)
  • Any contraindication to aspirin or clopidogrel therapy
  • Acute Febrile illness at the time of enrollment
  • Subject is pregnant or lactating or planning to become pregnant
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01097343

Locations
United States, North Carolina
University of North Carolina
Chapel Hill, North Carolina, United States, 27599
Sponsors and Collaborators
University of North Carolina, Chapel Hill
Investigators
Principal Investigator: Joseph Rossi, MD University of North Carolina, Chapel Hill
  More Information

No publications provided

Responsible Party: Joseph S. Rossi M.D., Assistant Professor of Medicine, University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier: NCT01097343     History of Changes
Other Study ID Numbers: 09-2104
Study First Received: March 30, 2010
Results First Received: July 9, 2012
Last Updated: February 26, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by University of North Carolina, Chapel Hill:
Clopidogrel pharmacogenomics study
Performing genetic study looking at clopidogrel resistance

Additional relevant MeSH terms:
Disease Susceptibility
Disease Attributes
Pathologic Processes
Clopidogrel
Ticlopidine
Platelet Aggregation Inhibitors
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Purinergic P2Y Receptor Antagonists
Purinergic P2 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Fibrinolytic Agents
Fibrin Modulating Agents
Cardiovascular Agents

ClinicalTrials.gov processed this record on August 26, 2014