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Trial record 93 of 1050 for:    clopidogrel

Pilot Study on the Effect of High Clopidogrel Maintenance Dosing (PREDICT)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01118793
Recruitment Status : Completed
First Posted : May 7, 2010
Last Update Posted : May 7, 2010
National Center for Research Resources (NCRR)
Information provided by:
Scripps Health

Brief Summary:
This is a Scripps pilot study on the effect of high clopidogrel maintenance dosing and its relationship to cytochrome P450 2C19 polymorphism status [STSI/CTSA].

Condition or disease Intervention/treatment
Coronary Artery Disease Drug: Clopidogrel

Detailed Description:

When added to aspirin, clopidogrel at a routine dose of 75 mg daily reduces the incidence of thrombotic vascular adverse events in patients with acute coronary syndromes and those undergoing percutaneous interventions (PCI). The observation that many patients have less than expected platelet inhibition with clopidogrel has given rise to the concept of clopidogrel resistance. Clopidogrel resistance is associated with increased adverse events such as stent thrombosis, post-stent ischemic events and periprocedural myocardial infarctions. Some patients can overcome the resistance with increasing the dose of clopidogrel. A higher maintenance dose (150 mg daily) in patients undergoing PCI results in superior platelet inhibition and may reduce cardiovascular events. Clopidogrel is a thienopyridine prodrug, which is converted to its active metabolite by several enzymes of the P450 family, including CYP2C19. The loss-of-function CYP2C19*2 (681 G>A) single nucleotide polymorphism (SNP), occurring as either a hetero- or homozygous allele, reduces the conversion of clopidogrel to its active metabolite. Two recent studies have shown an association between CYP2C19*2 polymorphism and lack of platelet inhibition with clopidogrel. These studies included healthy volunteers and patients undergoing elective PCI and demonstrated a prevalence of the CYP2C19*2 allele of 25-30%. Platelet inhibition was not affected by clopidogrel in those who carried the CYP2C19*2 polymorphism.

Our hypothesis is the following: Patients who are carriers of the loss-of-function CYP2C19*2 allele (heterozygous 1*/2* or homozygous 2*/2*) have decreased platelet inhibition on clopidogrel which cannot be overcome with increasing the maintenance dose from 75 mg to 150 mg daily.

The specific aim will include an evaluation of the anti-platelet response of a higher maintenance dose of clopidogrel (150 mg /daily) in patients who are resistant to the usual dose (75 mg/daily) and are either carriers or non-carriers of the CYP2C19*2 allele.

The study design will be a single center, prospective, observational pilot study. We will screen and enroll patients who are followed at Scripps Clinic and on chronic clopidogrel therapy. All patients will be eligible. A blood sample will be collected to perform DNA extraction and genotyping for the CYP2C19*2 polymorphism. Platelet function assays will be performed using VerifyNow point-of-care assay. We will recruit 60 patients with high platelet reactivity (PRU > 230): 30 wild-types (normal) and 30 carriers (heterozygous or homozygous) of the CYP2C19*2 polymorphism. These patients will be given 150 mg of clopidogrel for 1 week, at which time the platelet assay will be repeated. At that time, patients will be counseled by the study physicians regarding the potential risks and benefits of continuing to receive 150 mg of clopidogrel per day versus returning to the FDA approved dose of 75 mg daily.

The immediate objective is to evaluate the possibility of overcoming clopidogrel resistance in carriers of CYP2C19*2 with a higher maintenance dose. The long term objective is to improve patient care and outcomes using personalized medicine based on the individual's genotype.

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Study Type : Observational
Actual Enrollment : 41 participants
Observational Model: Case-Only
Time Perspective: Prospective
Official Title: PREDICT: Scripps Pilot Study on the Effect of High Clopidogrel Maintenance Dosing and Its Relationship to Cytochrome P450 2C19 Polymorphism Status
Study Start Date : December 2008
Actual Primary Completion Date : May 2010
Actual Study Completion Date : May 2010

Resource links provided by the National Library of Medicine

Group/Cohort Intervention/treatment
double dosing of Clopidogrel Drug: Clopidogrel
150 mg dosage of Clopidogrel for 7 to 10 days.
Other Name: Plavix

Biospecimen Retention:   Samples With DNA
Whole Blood

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Scripps Health patients having decresed platlet inhibition on clopidogrel

Inclusion Criteria:

  • Males and non-pregnant females between the ages of 18-85.
  • Patients able to give informed written consent.
  • Patients on clopidogrel for ≥ 7 days.

Exclusion Criteria:

  • Participation in a study of experimental therapy or device within prior 30 days.
  • Pregnant women or women of childbearing potential not using an acceptable method of contraception who have not been proven to have a negative pregnancy test result.
  • Inability to comply with all aspects of the protocol.
  • History of bleeding diathesis or evidence of active abnormal bleeding within previous 90 days.
  • Severe hypertension (systolic blood pressure > 200 mm Hg or diastolic blood pressure > 110 mm Hg) not adequately controlled on antihypertensive therapy.
  • Major surgery within the preceding 6 weeks.
  • History of stroke within 30 days or any history of hemorrhagic stroke.
  • History of intracranial neoplasm.
  • Current or planned administration of another parenteral GP IIb-IIIa inhibitor within 7 days of enrollment.
  • Known hypersensitivity to any component of the product.
  • Unstable angina with dynamic ST or T wave changes within 48 hours of enrollment.
  • Administration of LMWH within 8 hours prior to enrollment or UFH within 60 minutes unless a PPT < 50 secs or ACT < 150 secs.
  • On chronic anticoagulation (i.e. Coumadin).
  • Hemoglobin < 10 g/dL.
  • Hematocrit < 30%.
  • Platelet count < 100,000 mcL.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01118793

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United States, California
Scripp Health
La Jolla, California, United States, 92037
Sponsors and Collaborators
Scripps Health
National Center for Research Resources (NCRR)
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Principal Investigator: Colin Barker, MD Scripps Health

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Responsible Party: Colin Barker, MD, Scripps Health Identifier: NCT01118793     History of Changes
Other Study ID Numbers: HSC# 08-5083
1UL1RR025774-01 ( U.S. NIH Grant/Contract )
First Posted: May 7, 2010    Key Record Dates
Last Update Posted: May 7, 2010
Last Verified: May 2010
Additional relevant MeSH terms:
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Coronary Artery Disease
Coronary Disease
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Arterial Occlusive Diseases
Vascular Diseases
Platelet Aggregation Inhibitors
Purinergic P2Y Receptor Antagonists
Purinergic P2 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs