Aspirin Resistance in Coronary Artery Disease

NCT ID: NCT00753935

Last Updated: 2018-04-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 92 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-06-30
• Study Completion Date: 2014-03-31

Brief Summary

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.

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.

Conditions

Coronary Artery Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: SINGLE

Study Groups

Enteric-coated aspirin

patients received enteric-coated aspirin 81 mg qd for 2 weeks

Group Type: EXPERIMENTAL

enteric-coated aspirin

Intervention Type: DRUG

enteric-coated aspirin 81mg daily for 2 weeks

Chewable aspirin

Patients received chewable aspirin 81 mg qd for 2 weeks

Group Type: ACTIVE_COMPARATOR

Chewable aspirin

Intervention Type: DRUG

chewable aspirin 81mg daily for 2 weeks

Interventions

enteric-coated aspirin

enteric-coated aspirin 81mg daily for 2 weeks

Intervention Type: DRUG

Chewable aspirin

chewable aspirin 81mg daily for 2 weeks

Intervention Type: DRUG

Other Intervention Names

acetylsalicylic acid; acetylsalicylic acid

Eligibility Criteria

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

• Minimum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

Vanderbilt University

OTHER

Sponsor Role: lead

Responsible Party

John Oates

Professor of Medicine and Pharmacology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Mary B Taylor, MD, MSCI

Role: PRINCIPAL_INVESTIGATOR

Vanderbilt University

Locations

Vanderbilt University

Nashville, Tennessee, United States

Countries

United States

References

Smith JP, Haddad EV, Taylor MB, Oram D, Blakemore D, Chen Q, Boutaud O, Oates JA. Suboptimal inhibition of platelet cyclooxygenase-1 by aspirin in metabolic syndrome. Hypertension. 2012 Mar;59(3):719-25. doi: 10.1161/HYPERTENSIONAHA.111.181404. Epub 2012 Feb 6.

Reference Type: RESULT

PMID: 22311905 (View on PubMed)

Other Identifiers

5P50HL081009-03

Identifier Type: NIH

Identifier Source: secondary_id

View Link

040065

Identifier Type: -

Identifier Source: org_study_id