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Validation of an Assay to Measure Cyclooxygenase-1 Activity

This study has been completed.
Information provided by (Responsible Party):
John Oates, Vanderbilt University Identifier:
First received: September 26, 2008
Last updated: December 4, 2015
Last verified: December 2015
The purpose of this study is to obtain a reference range for a newly developed assay of ex vivo platelet COX-1 activity in normal volunteers taking a routine clinical dose of aspirin.

Condition Intervention
Drug: Enteric-coated aspirin
Drug: Chewable aspirin

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Investigator)
Official Title: Validation of an Ex Vivo Cyclooxygenase-1 Catalytic Assay in Humans

Resource links provided by NLM:

Further study details as provided by Vanderbilt University:

Primary Outcome Measures:
  • d8-thromboxane B2 generated in ex vivo platelet COX-1 catalytic assay [ Time Frame: Baseline and after 2 weeks of aspirin ] [ Designated as safety issue: No ]
    measure d8-thromboxane B2

Secondary Outcome Measures:
  • Platelet aggregation by optical aggregometry [ Time Frame: Baseline and after 2 weeks of aspirin ] [ Designated as safety issue: No ]
    Measure platelet aggregation

  • Serum thromboxane B2 [ Time Frame: Baseline and after 2 weeks of aspirin ] [ Designated as safety issue: No ]
    Measure serum thromboxane B2

  • Urinary 11-dehydro-thromboxane B2 [ Time Frame: Baseline and after 2 weeks of aspirin ] [ Designated as safety issue: No ]
    Measure Urinary 11-dehydro-thromboxane B2

  • Urinary prostacyclin metabolite [ Time Frame: Baseline and after 2 weeks of aspirin ] [ Designated as safety issue: No ]
    Measure Urinary prostacyclin metabolite

Enrollment: 60
Study Start Date: May 2007
Study Completion Date: January 2010
Primary Completion Date: May 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Enteric-coated aspirin
81 mg daily for 2 weeks
Drug: Enteric-coated aspirin
enteric-coated aspirin 81mg daily for 2 weeks
Other Name: acetylsalicylic acid
Active Comparator: Chewable aspirin
81 mg daily for 2 weeks
Drug: Chewable aspirin
chewable aspirin 81mg daily for 2 weeks
Other Name: acetylsalicylic acid

Detailed Description:

Aspirin has been shown to reduce cardiovascular events in at-risk individuals, but some aspirin-treated patients fail to exhibit expected changes in bleeding time and platelet aggregation. Recent evidence has correlated aspirin "non-response" to poor cardiovascular outcomes.

In order to study the mechanisms of aspirin resistance, an assay is needed to measure the catalytic activity of platelet cyclooxygenase (which should be inhibited by aspirin). A common assay in general use is the measurement of thromboxane B2 production in clotting whole blood. This measure, however, is influenced by genetic and environmental variations in the glass-activated coagulation pathway, albumin binding capacity, platelet activation pathways, arachidonic acid pools, and phospholipase activity.

Our laboratory has developed a direct assay of platelet cyclooxygenase (COX-1) activity that is not influenced by these variations. This study will generate a reference range in normal volunteers taking a routine clinical dose of aspirin (81mg daily) for this assay. In addition, by using two aspirin formulations (enteric-coated and chewable), the study design additionally allows the secondary comparison of the effects of these two formulations on COX-1 inhibition.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes

Inclusion Criteria:

  • Non-smoker
  • No chronic medical illness
  • No chronic medications

Exclusion Criteria:

  • Aspirin/NSAID use in preceding 14 days
  • History of chronic NSAID use
  • Currently taking NSAIDs, opioid analgesics, corticosteroids, or anticoagulants
  • History of coronary artery disease, myocardial infarction, coronary artery bypass grafting, percutaneous angioplasty, diabetes mellitus, or stroke.
  • History of hypertension
  • Body mass index > 35
  • History of gastric, duodenal, or esophageal ulcers or serious gastrointestinal bleed
  • History of frequent headaches, pain syndrome, or other condition requiring frequent use of analgesics
  • History of adverse reactions to aspirin
  • Screening platelet count < 100,000/ul or > 500,000/ul
  • Screening hematocrit < 35% or > 50%
  • Weight less than 110 pounds
  • Pregnant females
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Please refer to this study by its identifier: NCT00761891

United States, Tennessee
Vanderbilt University
Nashville, Tennessee, United States, 37232
Sponsors and Collaborators
Vanderbilt University
Principal Investigator: John A Oates, MD Vanderbilt University
  More Information

Responsible Party: John Oates, Professor of Medicine and Pharmacology, Vanderbilt University Identifier: NCT00761891     History of Changes
Other Study ID Numbers: 061190 
Study First Received: September 26, 2008
Last Updated: December 4, 2015
Health Authority: United States: Institutional Review Board

Keywords provided by Vanderbilt University:
aspirin resistance
aspirin nonresponse
Normal volunteers

Additional relevant MeSH terms:
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
Antipyretics processed this record on October 21, 2016