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Pharmacogenomics of Antiplatelet Response - I (PARes-I)

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: NCT01815008
Recruitment Status : Completed
First Posted : March 20, 2013
Results First Posted : January 9, 2017
Last Update Posted : January 9, 2017
Information provided by (Responsible Party):
Rehan Qayyum, Johns Hopkins University

Brief Summary:
This clinical trial is examining the role of genetic polymorphism on the effect of clopidogrel (with or without aspirin) on platelet response in persons at high-risk for myocardial infarction or stroke due to family history of early-onset coronary artery disease.

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

Detailed Description:
The main goal of this study is to explore the impact of the PEAR1 genetic variant (rs12041331) on responsiveness to clopidogrel. The investigators will further assess the role of other genetic variants in determining the response to single or dual anti-platelet therapy. Apparently healthy subjects (N= 2108) from high-risk families are being (a) identified from a proband with early-onset CAD and (b) genotyped on the Illumina 1 million platform, with imputation to 2.5 million single nucleotide polymorphisms. The investigators plan to characterize the variance in platelet aggregation to multiple agonists (ADP, collagen, and arachidonic acid) after 1-week therapy with clopidogrel in a high-risk subset of GeneSTAR subjects (N=100). The investigators further plan to determine the extent to which variants identified in the PEAR1 gene modify platelet responsiveness to inhibition by clopidogrel in this high-risk subset. In addition, the investigators aim is to determine the extent to which variants in other recently discovered genes, by themselves, and in combination with PEAR1, modify platelet responsiveness to clopidogrel alone and with aspirin in this high-risk subset. Lastly, the investigators also want to determine what changes in platelet mRNA are produced by aspirin alone and by aspirin with clopidogrel.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 19 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Study Start Date : October 2012
Actual Primary Completion Date : June 2014
Actual Study Completion Date : June 2014

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Clopidogrel
Clopidogrel 75 mg daily by mouth for 1 week then Clopidogrel 75 mg daily with aspirin 81 mg daily
Drug: Clopidogrel
Clopidogrel 75 mg daily
Other Name: Plavix

Drug: Aspirin
Aspirin 81 mg daily

Primary Outcome Measures :
  1. Difference in ADP-induced Platelet Aggregation [ Time Frame: at baseline and at 1 week ]
    ADP-induced platelet aggregation will be measured using impedance aggregometry in whole blood before and after 1-week of clopidogrel. The difference between the baseline and after clopidogrel therapy will be determined. Higher impedance represent higher platelet aggregation.

Secondary Outcome Measures :
  1. Difference in Arachidonic Acid-induced Platelet Aggregation [ Time Frame: At baseline and after 1-week ]
    Arachidonic Acid-induced platelet aggregation will be measured using impedance aggregometry in whole blood before and after 1-week of clopidogrel. The difference between the baseline and after clopidogrel therapy will be determined

  2. Difference in Collagen-induced Platelet Aggregation [ Time Frame: At Baseline and at 1 week ]
    Collagen-induced platelet aggregation will be measured using impedance aggregometry in whole blood before and after 1-week of clopidogrel. The difference between the baseline and after clopidogrel therapy will be determined

  3. Changes in Platelet Transcriptome With Clopidogrel [ Time Frame: At baseline and at 1 week ]
    Platelet transcriptome will be examined before and after 1 week of therapy with clopidogrel and differences will be determined

Information from the National Library of Medicine

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Ages Eligible for Study:   45 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Participants from the GeneSTAR cohort
  • Unaffected with no overt coronary artery disease or serious vascular event (stroke or peripheral vascular disease diagnosis
  • Presence of an occult coronary artery disease phenotype as defined by coronary artery calcium scores about the MESA (Multiethnic Study of Atherosclerosis) 75th percentile for age sex, and race or ≥ 1 stenoses in any of the major coronary arteries or main branches of > 50%, or coronary plaque volumetric scores above our own 75th percentile, or any combination on cardiac computed tomographic angiography (performed recently as part of the GeneSTAR study and present for all persons being recruited)/
  • Presence of occult cerebrovascular disease defined as presence of white matter hyperintensities (WMH) thought to represent ischemic small vessel cerebrovascular disease, and /or the presence of lacunes (old small strokes), or the presence of an Atherosclerosis Risk in Communities Study (ARIC) silent stroke score on a visual analogue scales of 4 or more (on a scale of 0-9).
  • Women who are postmenopausal.
  • Women who use a reliable contraceptive method; a reliable contraceptive method will be defined as personal history of tubal ligation, ongoing use of intra-uterine device, or ongoing use of oral contraceptive pills.

Exclusion Criteria:

  • Presence of any CAD or stroke, transient ischemic attacks, peripheral arterial disease
  • Persons taking aspirin, NSAIDS, or any anti-coagulants who are medically unable to stop them for a two week pre-trial
  • A history of allergy to aspirin or clopidogrel
  • Weight < 60kg
  • Age < 45 and > 75 years of age
  • A history of recent or any active bleeding
  • Serious or current co-morbidity (AIDS, cancer)
  • Pregnant women as determined by urine dipstick pregnancy test
  • Any aneurysms on cranial magnetic resonance imaging/magnetic resonance angiography (obtained recently in the GeneSTAR participants)
  • Blood pressure above >=159/95mmHg
  • History of a gastric or duodenal ulcer, or significant gastrointestinal disease, like regional enteritis
  • Mental incompetence to make a decision to participate (developmentally disabled, and persons with diagnosed psychiatric disorders—documented in primary care records).

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): NCT01815008

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United States, Maryland
Johns Hopkins University School of Medicine
Baltimore, Maryland, United States, 21287
Sponsors and Collaborators
Johns Hopkins University
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Principal Investigator: Rehan Qayyum, MD Johns Hopkins University

Additional Information:
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Responsible Party: Rehan Qayyum, Assistant Professor of Medicine, Johns Hopkins University Identifier: NCT01815008    
Other Study ID Numbers: K23HL105897-PARes-I
K23HL105897 ( U.S. NIH Grant/Contract )
First Posted: March 20, 2013    Key Record Dates
Results First Posted: January 9, 2017
Last Update Posted: January 9, 2017
Last Verified: November 2016
Keywords provided by Rehan Qayyum, Johns Hopkins University:
Platelet aggregation
Platelet transcriptome
Additional relevant MeSH terms:
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Purinergic P2Y Receptor Antagonists
Purinergic P2 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Coronary Artery Disease
Coronary Disease
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Arterial Occlusive Diseases
Vascular 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
Neurotransmitter Agents