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Clopidogrel Pharmacogenetics Bench to Bedside - A Practical Application


N/A
20 Years
70 Years
Not Enrolling
Both
Metabolism of Clopidogrel

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Trial Information

Clopidogrel Pharmacogenetics Bench to Bedside - A Practical Application


Clopidogrel is a prodrug with high inter-individual response variability. Clopidogrel is
converted to an active drug through an enzyme encoded by the gene named CYP2C19.
Individuals with genetically-impaired CYP2C19 metabolism have lower capacity to convert the
prodrug to its active form. Consequently, these individuals have lower blood levels of the
activated form of clopidogrel, diminished antiplatelet responses, and higher rates of
cardiovascular events and stent thrombosis. Increasing doses of clopidogrel in such
patients represents a possible approach to managing the gene-drug interaction.

The purpose of this study is to evaluate whether increasing the dose of clopidogrel
increases antiplatelet responses and active metabolite exposure in individuals with
genetically reduced CYP2C19 metabolism relative to those with normal CYP2C19 metabolism.

The primary objective is to assess changes in clopidogrel response and exposure at three
clopidogrel dose levels and with coadministration of omeprazole.


Inclusion Criteria:



- Amish men or women between 20 and 70 years of age who participated in PAPI

Exclusion Criteria:

- Severe hypertension (bp > 160/95 mm Hg)

- Co-existing malignancy

- AST or ALT > 2 times normal

- Creatinine >2.0

- Hct < 32 or Hct > 50

- TSH < 0.40 or >5.50

- History of bleeding disorder or gastrointestinal bleeding

- History of unstable angina, MI, angioplasty, coronary artery bypass surgery

- History of atrial fibrillation, stroke or transient ischemic attacks or deep vein
thrombosis

- Type 2 diabetes

- Thrombocytosis (platelet count > 500,000) or thrombocytopenia (platelet count <
150,000)

- Surgery within six months

- Clopidogrel allergy

- Pregnant women

- Currently breast feeding

- Omeprazole allergy

- Prospective participants taking medications that would affect the outcome(s) to be
measured and who cannot willingly and safely, in the opinion of the treating
physician and study physician, discontinue these medications for 1 week prior to
protocol initiation, or who are taking vitamins and/or other supplements and who are
unwilling to discontinue their use for at least 1 week prior to study

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Change in platelet aggregation following therapy with Clopidogrel

Outcome Description:

platelet aggregation will be measured at baseline and at 4-hours post-dose of clopidogrel on day 1 and at 4-hours post-dose of clopidogrel on day 8. The primary endpoint of this study will be the change in maximal platelet aggregation 4-hours post-dose (MPA4; units are a percentage) on day 8 of each study period compared to baseline.

Outcome Time Frame:

Baseline, Day 1, Day 8

Safety Issue:

Yes

Principal Investigator

Richard B Horenstein, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Maryland

Authority:

United States: Institutional Review Board

Study ID:

HP-00044487

NCT ID:

NCT01341600

Start Date:

July 2010

Completion Date:

May 2011

Related Keywords:

  • Metabolism of Clopidogrel
  • Clopidogrel
  • Pharmacogenetics
  • Platelets
  • Healthy Subjects

Name

Location
Amish Research Clinic Lancaster, Pennsylvania  17601