Now Available: Final Rule for FDAAA 801 and NIH Policy on Clinical Trial Reporting

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

This study has been completed.
Sponsor:
Collaborators:
National Institute of General Medical Sciences (NIGMS)
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Alan Shuldiner, University of Maryland
ClinicalTrials.gov Identifier:
NCT00799396
First received: November 26, 2008
Last updated: March 23, 2016
Last verified: March 2016
  Purpose
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 Intervention Phase
Platelet Aggregation Inhibitors
Coronary Heart Disease
Drug: Clopidogrel
Drug: Aspirin
Phase 4

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacodynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Pharmacogenomics of Anti-Platelet Interventions (The PAPI Study)

Resource links provided by NLM:


Further study details as provided by University of Maryland:

Primary Outcome Measures:
  • Changes in Platelet Function in Response to Clopidogrel [ Time Frame: Measured at baseline, and after clopidogrel treatment ] [ Designated as safety issue: No ]
    Baseline minus post clopidogrel/pre-aspirin platelet rich plasma (PRP) maximum aggregation.

  • Changes in Platelet Function in Response to Clopidogrel Plus Aspirin [ Time Frame: Measured at baseline, and after clopidogrel plus aspirin treatment ] [ Designated as safety issue: No ]
    Baseline minus post clopidogrel/post-aspirin platelet rich plasma (PRP) maximum aggregation


Enrollment: 682
Study Start Date: July 2006
Study Completion Date: February 2012
Primary Completion Date: February 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   20 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00799396

Locations
United States, Pennsylvania
Amish Research Clinic
Lancaster, Pennsylvania, United States, 17601
Sponsors and Collaborators
University of Maryland
National Institute of General Medical Sciences (NIGMS)
National Heart, Lung, and Blood Institute (NHLBI)
Investigators
Principal Investigator: Alan R. Shuldiner, MD University of Maryland
  More Information

Additional Information:
Publications:

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
ClinicalTrials.gov Identifier: NCT00799396     History of Changes
Other Study ID Numbers: HP-00043419  U01 HL074518-01  U01GM074518 
Study First Received: November 26, 2008
Results First Received: February 18, 2016
Last Updated: March 23, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Heart Diseases
Coronary Disease
Coronary Artery Disease
Myocardial Ischemia
Cardiovascular Diseases
Vascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Aspirin
Clopidogrel
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
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
Antipyretics
Purinergic P2Y Receptor Antagonists
Purinergic P2 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents

ClinicalTrials.gov processed this record on September 29, 2016