African-American Pharmacogenetics (AA Genetic)

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.

Study Overview

• Status: Unknown
• Conditions: Acute Coronary Syndrome
• Intervention / Treatment: Other: Genotyping and platelet reactivity testing with the VerifyNow P2Y12 assay

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.

• Study Type: Observational
• Enrollment (Anticipated): 200

Contacts and Locations

Study Locations

• United States
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Washington Hospital Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

African-american versus Caucasian patients undergoing percutaneous coronary intervention and receiving clopidogrel or prasugrel.

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
African-American on clopidogrel	Other: Genotyping and platelet reactivity testing with the VerifyNow P2Y12 assay; 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.
African-American on prasugrel	Other: Genotyping and platelet reactivity testing with the VerifyNow P2Y12 assay; 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.
Caucasian on clopidogrel	Other: Genotyping and platelet reactivity testing with the VerifyNow P2Y12 assay; 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.
Caucasian on prasugrel	Other: Genotyping and platelet reactivity testing with the VerifyNow P2Y12 assay; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Distribution of CYP polymorphisms	CYP polymorphisms will be classified by their known effects upon enzyme function, using the consensus star-allele nomenclature. More specifically, patients will be classified as a "poor metabolizer" if they possess at least one CYP allele known to be associated with reduced function of that particular CYP enzyme. Allele frequencies will then be compared between African-american and Caucasian patients.	During hospital stay; average hospital stay is less than 48 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Platelet reactivity	The secondary exploratory objective is to assess for associations between "poor metabolizer" CYP genotypes and the levels of post-thienopyridine platelet reactivity.	During hospital stay; average hospital stay is less than 48 hours

Collaborators and Investigators

• Sponsor: Medstar Health Research Institute
• Investigators: Principal Investigator: Ron Waksman, MD, MedStar Health Research Institute

Study record dates

Study Major Dates

• Study Start: November 1, 2011
• Primary Completion (Anticipated): June 1, 2016
• Study Completion (Anticipated): June 1, 2016

Study Registration Dates

• First Submitted: July 29, 2011
• First Submitted That Met QC Criteria: August 2, 2011
• First Posted (Estimate): August 3, 2011

Study Record Updates

• Last Update Posted (Estimate): August 11, 2014
• Last Update Submitted That Met QC Criteria: August 8, 2014
• Last Verified: August 1, 2014

More Information

Terms related to this study

• Keywords: Platelet reactivity; Genotyping
• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Acute Coronary Syndrome
• Other Study ID Numbers: AA Genetic