Clinical trial NCT01408121: African-American Pharmacogenetics
Official title: African-American Pharmacogenetics
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Acute Coronary Syndrome
Keywords: Platelet reactivity
Genotyping
Lead sponsor: Medstar Health Research Institute
Sponsor class: OTHER
First posted: 2011-08-03
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: African-american versus Caucasian patients undergoing percutaneous coronary intervention and receiving clopidogrel or prasugrel.

Brief summary: This is a genetic and platelet reactivity study of African-American versus Caucasian patients undergoing percutaneous coronary intervention and receiving clopidogrel or prasugrel. The investigators aim is twofold: to describe differences in allele frequencies between African-Americans and Caucasians, and to explore associations of platelet reactivity and genetic polymorphisms in these two groups.

Detailed description: The investigators propose a pharmacogenetic cohort study of 100 African-American versus 100 Caucasian patients presenting with an acute coronary syndrome, receiving clopidogrel or prasugrel and undergoing PCI. The study will have four arms: African-American on clopidogrel; African-American on prasugrel; Caucasian on clopidogrel; and Caucasian on prasugrel. All patients will undergo genotyping and platelet reactivity testing with the VerifyNow P2Y12 assay, at least 6 hours after receiving a thienopyridine loading dose, but before hospital discharge. All patients will be treated with aspirin 325 mg/day as well.

Race determination will be based on a patient's self-report, but patients enrolled in the trial must also report that all four of their grandparents were of the same race as theirs. Other races (Asian, Native American, et al) will be excluded from this study.

Eligibility criteria: Inclusion Criteria:

1. Patients age 18 or older, of both genders
2. Presenting with an ACS, defined as at least two of the following:

   * symptoms consistent with myocardial ischemia;
   * ST segment elevation or depression of at least 1 mm in 2 or more contiguous leads on EKG;
   * a cardiac troponin I level above upper limit of normal.
3. Self-reported African-american or Caucasian race

   a. all 4 grandparents of same race
4. No contraindications to prasugrel therapy.
5. Patient is scheduled for, or has already undergone, PCI.

Exclusion Criteria:

1. Known allergies to aspirin, clopidogrel, or prasugrel.
2. Patient known to be pregnant or lactating.
3. Patient with known history of bleeding diathesis or currently active bleeding.
4. Platelet count \<100,000/mm at the time of enrollment.
5. Hematocrit \<25% at the time of enrollment.
6. On warfarin therapy at the time of PCI, or patient likely to require warfarin therapy post-PCI.
7. Received fibrinolytics within the past 48 hours.
8. Received a glycoprotein IIb/IIIa inhibitor within the past 48 hours, or if such a strategy for PCI involving a glycoprotein IIb/IIIa inhibitor is planned.
9. Taking maintenance thienopyridine therapy in the previous 5 days.
10. Known blood transfusion within the preceding 10 days.
11. Patients treated with non-steroidal anti-inflammatory drugs (NSAIDS) within the previous 5 days.
12. Patients with known chronic liver disease.
13. Age greater than 75 years
14. Body weight less than 60 kg
15. History of stroke or transient ischemic attack
16. Surgery planned within 1 month
17. Patient likely to require coronary artery bypass grafting
18. Any significant medical condition that, in the investigator's opinion, may interfere with the patient's optimal participation in the study.

Primary outcomes:
measure: Distribution of CYP polymorphisms
timeFrame: During hospital stay; average hospital stay is less than 48 hours
Secondary outcomes:
measure: Platelet reactivity
timeFrame: During hospital stay; average hospital stay is less than 48 hours
Other outcomes:
Locations:
city: Washington
country: United States
facility: Washington Hospital Center
state: District of Columbia
Study officials:
affiliation: Medstar Health Research Institute
name: Ron Waksman, MD
role: PRINCIPAL_INVESTIGATOR
References: