Aspirin Resistance in Coronary Artery Disease

March 19, 2018 updated by: John Oates, Vanderbilt University

Evaluation of Aspirin Resistance at a Molecular Level in Aspirin-Treated Patients With Coronary Artery Disease

The purpose of this study is to evaluate possible mechanisms of aspirin resistance at a molecular level in aspirin-treated patients with coronary artery disease. We hypothesize that certain patient characteristics associate with aspirin resistance. In addition, we will compare the effects of enteric-coated aspirin and chewable aspirin.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Aspirin is commonly used for its antithrombotic effects in patients at risk for cardiovascular events. Its primary mechanism of action is the irreversible acetylation of platelet cyclooxygenase-1, thereby inhibiting platelet production of thromboxane A2, a potent vasoconstrictor and activator of platelets. Thromboxane A2, the major product of cyclooxygenase cytochrome oxidase (COX-1) in platelets, induces platelet aggregation. Thromboxane B2 is an inactive metabolite/product of thromboxane A2. This primary outcome measures the extent of inhibition of platelet COX-1 by measuring the amount of the metabolite thromboxane B2 in serum.

Previous studies have demonstrated that many patients have recurrent events despite treatment with aspirin, which has been termed "aspirin resistance" or "aspirin nonresponse." This study addresses some of the possible mechanisms for aspirin nonresponse; specifically, we will test the hypothesis that aspirin nonresponse results from states that produce high peroxide concentrations ("oxidative stress") in platelets. In addition, we will evaluate the effect of enteric coating on the pharmacologic efficacy of aspirin in patients with coronary artery disease.

Study Type

Interventional

Enrollment (Actual)

92

Phase

  • Early Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Vanderbilt University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

40 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • On aspirin 81-325mg daily at time of enrollment
  • Documented stable coronary artery disease or > 6 months after coronary artery bypass grafting or interventional cardiac procedure
  • Written informed consent

Exclusion Criteria:

  • Pre-menopausal female
  • Renal disease (creatinine >= 2 mg/dl)
  • Anemia (Hematocrit < 30%)
  • Thrombocytopenia (platelet count < 135,000/ul)
  • Use of NSAIDs or coxibs within the previous 2 weeks
  • Concurrent use of other anti-platelet agents
  • Uncontrolled hypertension (systolic BP > 180 mmHg)
  • Decompensated congestive heart failure
  • Recent coronary syndrome (< 6 months)
  • History of significant GI bleeding

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Enteric-coated aspirin
patients received enteric-coated aspirin 81 mg qd for 2 weeks
Drug: enteric-coated aspirin
enteric-coated aspirin 81mg daily for 2 weeks
Other Names:
  • acetylsalicylic acid
Active Comparator: Chewable aspirin
Patients received chewable aspirin 81 mg qd for 2 weeks
Drug: Chewable aspirin
chewable aspirin 81mg daily for 2 weeks
Other Names:
  • acetylsalicylic acid

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Serum Thromboxane B2
Time Frame: after 2 weeks on aspirin
Thromboxane A2, the major product of cyclooxygenase cytochrome oxidase (COX-1) in platelets, induces platelet aggregation. Thromboxane B2 is an inactive metabolite/product of thromboxane A2. This primary outcome measures the extent of inhibition of platelet COX-1 by measuring the amount of the metabolite thromboxane B2 in serum.
after 2 weeks on aspirin

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Vanderbilt University

Collaborators

National Heart, Lung, and Blood Institute (NHLBI)

Investigators

  • Principal Investigator: Mary B Taylor, MD, MSCI, Vanderbilt University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2006

Primary Completion (Actual)

August 1, 2011

Study Completion (Actual)

March 1, 2014

Study Registration Dates

First Submitted

September 15, 2008

First Submitted That Met QC Criteria

September 15, 2008

First Posted (Estimate)

September 17, 2008

Study Record Updates

Last Update Posted (Actual)

April 19, 2018

Last Update Submitted That Met QC Criteria

March 19, 2018

Last Verified

March 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 040065
  • 5P50HL081009-03 (U.S. NIH Grant/Contract)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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