Working…
ClinicalTrials.gov
ClinicalTrials.gov 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.
 
ClinicalTrials.gov Identifier: NCT00799396
Recruitment Status : Completed
First Posted : November 27, 2008
Results First Posted : March 28, 2016
Last Update Posted : August 22, 2019
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, College Park

Tracking Information
First Submitted Date  ICMJE November 26, 2008
First Posted Date  ICMJE November 27, 2008
Results First Submitted Date  ICMJE February 18, 2016
Results First Posted Date  ICMJE March 28, 2016
Last Update Posted Date August 22, 2019
Study Start Date  ICMJE July 2006
Actual Primary Completion Date February 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 23, 2016)
  • 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.
  • 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
Original Primary Outcome Measures  ICMJE
 (submitted: November 26, 2008)
Changes in platelet function in response to clopidogrel and clopidogrel plus aspirin [ Time Frame: Measured at baseline, before and after clopidogrel treatment, and after clopidogrel plus aspirin treatment ]
Change History Complete list of historical versions of study NCT00799396 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Determining Genetic Role in Treatment Response to Anti-Platelet Interventions (The PAPI Study)
Official Title  ICMJE Pharmacogenomics of Anti-Platelet Interventions (The PAPI Study)
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Platelet Aggregation Inhibitors
  • Coronary Heart Disease
Intervention  ICMJE
  • 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
Study Arms  ICMJE Experimental: Overall Study
Participants will receive clopidogrel treatment alone, followed by clopidogrel plus aspirin treatment on the last day of treatment.
Interventions:
  • Drug: Clopidogrel
  • Drug: Aspirin
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 23, 2016)
682
Original Estimated Enrollment  ICMJE
 (submitted: November 26, 2008)
600
Actual Study Completion Date  ICMJE February 2012
Actual Primary Completion Date February 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 20 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00799396
Other Study ID Numbers  ICMJE HP-00043419
U01 HL074518-01
U01GM074518 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Alan Shuldiner, University of Maryland, College Park
Study Sponsor  ICMJE University of Maryland, Baltimore
Collaborators  ICMJE
  • National Institute of General Medical Sciences (NIGMS)
  • National Heart, Lung, and Blood Institute (NHLBI)
Investigators  ICMJE
Principal Investigator: Alan R. Shuldiner, MD University of Maryland, College Park
PRS Account University of Maryland, Baltimore
Verification Date August 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP