Determining Genetic Role in Treatment Response to Anti-Platelet Interventions (The PAPI Study)

University of Maryland Baltimore (UMB)

Status and phase

Completed

Phase 4

Conditions

Coronary Heart Disease

Platelet Aggregation Inhibitors

Treatments

Drug: Aspirin

Drug: Clopidogrel

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00799396

U01 HL074518-01

U01GM074518 (U.S. NIH Grant/Contract)

HP-00043419

Details and patient eligibility

About

One of the most common ways for preventing coronary heart disease (CHD) is to take aspirin or clopidogrel. However, studies have shown that not all people respond to these medications. The variance in treatment response may be linked to genetics. This study will examine the effects of aspirin and clopidogrel in a population whose genes are well known in order to determine the role that genes play in treatment responses.

Full description

CHD is the leading cause of death in the United States. Anti-platelet agents lessen platelet aggregation and are used commonly to prevent recurrent CHD events. Two of the most common anti-platelet agents are aspirin and clopidogrel. However, up to 25% to 30% of people do not respond to these medications. Evidence indicates that treatment response may be related to genetics. The purpose of this study is to determine specific gene variants that predict response to aspirin and clopidogrel therapy.

This study is part of a larger group of studies called the Pharmacogenomics Research Network (PGRN). Participants will include the Old Order Amish of Lancaster, Pennsylvania. They are well suited for genetic studies because they are a homogenous, closed, founder population. Participants will receive 300 mg of clopidogrel on the first day, then 75 mg of clopidogrel per day for the next 6 days. On the last day of clopidogrel treatment, participants will take a single dose of 324 mg aspirin. Participants will undergo platelet function tests before and after clopidogrel alone, and then again after taking clopidogrel plus aspirin. Using the gene variation profiles across the genome, researchers will analyze which genes correspond to treatment response.

Enrollment

682 patients

Sex

All

Ages

20+ years old

Volunteers

Accepts Healthy Volunteers

Inclusion criteria

Of Old Order Amish descent

Exclusion criteria

Currently pregnant or less than 6 months have passed since delivery
Has a history of a bleeding disorder or major spontaneous bleed, such as peptic ulcer, epistasis, or intracranial bleed
Has severe hypertension, defined by a blood pressure above 160/95 mm Hg, making it unethical not to recommend prompt treatment
Takes medications that would affect the outcome(s) to be measured and cannot willingly and safely, in the opinion of the treating physician and study physician, discontinue these medications for 1 week prior to protocol initiation
Is taking vitamins or other supplements and is unwilling to discontinue their use for at least 1 week prior to study
Has a coexisting malignancy
Has a creatinine level greater than 2.0 mg/dl, aspartate transaminase (AST) or alanine transaminase (ALT) greater than two times the upper limit of normal, hematocrit less than 32%, or a thyroid-stimulating hormone (TSH) less than 0.4 or greater than 5.5 mIU/L
Has a bleeding disorder or history of gastrointestinal bleeding or other major bleeding episode
Is currently taking aspirin, clopidogrel, or other anti-coagulant, such as warfarin, heparin, or GPIIb/IIIa antagonists, and have conditions that might place them at increased risk from withdrawal of these medications 14 days prior to protocol initiation, including history of unstable angina, heart attack, angioplasty (including stent placement), coronary artery bypass surgery, atrial fibrillation, stroke or transient ischemic attacks, diabetes, or deep vein thrombosis or other thrombosis
Has polycythemia, or thrombocytosis, defined by a platelet count greater than 500,000
Has thrombocytopenia, defined by a platelet count less than 75,000
Has had surgery within the last 6 months
Has an aspirin or clopidogrel allergy
Currently breast feeding