Working… Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00799396
Recruitment Status : Completed
First Posted : November 27, 2008
Results First Posted : March 28, 2016
Last Update Posted : August 22, 2019
National Institute of General Medical Sciences (NIGMS)
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Alan Shuldiner, University of Maryland, College Park

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.

Condition or disease Intervention/treatment Phase
Platelet Aggregation Inhibitors Coronary Heart Disease Drug: Clopidogrel Drug: Aspirin Phase 4

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 682 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Pharmacogenomics of Anti-Platelet Interventions (The PAPI Study)
Study Start Date : July 2006
Actual Primary Completion Date : February 2012
Actual Study Completion Date : February 2012

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Overall Study
Participants will receive clopidogrel treatment alone, followed by clopidogrel plus aspirin treatment on the last day of treatment.
Drug: Clopidogrel
300 mg on first day, then 75 mg per day for the next 6 days

Drug: Aspirin
Single dose of 324 mg on the last day of clopidogrel treatment

Primary Outcome Measures :
  1. Changes in Platelet Function in Response to Clopidogrel [ Time Frame: Measured at baseline, and after clopidogrel treatment ]
    Baseline minus post clopidogrel/pre-aspirin platelet rich plasma (PRP) maximum aggregation.

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

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   20 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00799396

Layout table for location information
United States, Pennsylvania
Amish Research Clinic
Lancaster, Pennsylvania, United States, 17601
Sponsors and Collaborators
University of Maryland, Baltimore
National Institute of General Medical Sciences (NIGMS)
National Heart, Lung, and Blood Institute (NHLBI)
Layout table for investigator information
Principal Investigator: Alan R. Shuldiner, MD University of Maryland, College Park
Additional Information:
Publications of Results:

Publications automatically indexed to this study by Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Alan Shuldiner, Associate Dean for Personalized Medicine; Director, Program in Personalized and Genomic Medicine; Head, Division of Endocrinology, Diabetes and Nutrition, University of Maryland, College Park Identifier: NCT00799396    
Other Study ID Numbers: HP-00043419
U01 HL074518-01
U01GM074518 ( U.S. NIH Grant/Contract )
First Posted: November 27, 2008    Key Record Dates
Results First Posted: March 28, 2016
Last Update Posted: August 22, 2019
Last Verified: August 2019
Additional relevant MeSH terms:
Layout table for MeSH terms
Heart Diseases
Coronary Disease
Coronary Artery Disease
Myocardial Ischemia
Cardiovascular Diseases
Vascular Diseases
Arterial Occlusive Diseases
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Platelet Aggregation Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Purinergic P2Y Receptor Antagonists
Purinergic P2 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents