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

Phase 4

Completed

Conditions: Platelet Aggregation Inhibitors
Coronary Heart Disease

Interventions: Drug: Clopidogrel
Drug: Aspirin

Registration Number: NCT00799396

Lead Sponsor: University of Maryland, Baltimore

Brief Summary: 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.

Detailed 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 682

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Overall Study	Aspirin	Participants will receive clopidogrel treatment alone, followed by clopidogrel plus aspirin treatment on the last day of treatment.
Overall Study	Clopidogrel	Participants will receive clopidogrel treatment alone, followed by clopidogrel plus aspirin treatment on the last day of treatment.

Primary Outcome Measures

Name	Time	Method
Changes in Platelet Function in Response to Clopidogrel	Measured at baseline, and after clopidogrel treatment	Baseline minus post clopidogrel/pre-aspirin platelet rich plasma (PRP) maximum aggregation.
Changes in Platelet Function in Response to Clopidogrel Plus Aspirin	Measured at baseline, and after clopidogrel plus aspirin treatment	Baseline minus post clopidogrel/post-aspirin platelet rich plasma (PRP) maximum aggregation

Secondary Outcome Measures