Loss of Effect of Aspirin on Platelet Aggregation During Chronic Administration

Aspirin has shown to be beneficial to some patients with certain diseases such as coronary artery disease or stroke. We are investigating how aspirin works on regulating platelets and thromboxane over time at different doses. We hope to find the best dose of aspirin and/or other medications to help people who are at risk for heart attack or stroke.

Study Overview

• Status: Terminated
• Conditions: Platelet Aggregation
• Intervention / Treatment: Drug: aspirin; Drug: aspirin; Drug: placebo

Detailed Description

he purpose of the study is to better understand the mechanism for failure of daily aspirin administration to prevent cardiovascular events in some at risk individuals. We seek to describe the effect of chronic aspirin administration at varying doses on platelet aggregation. This will help to define mechanisms for aspirin failure and to pursue possible alternative therapies in patients who fail to respond to aspirin therapy.

We hypothesize that (1) inhibition by aspirin (ASA) of ex vivo-induced platelet aggregation varies in a predictable time and dose dependent manner, (2) thromboxane and prostacyclin production is inhibited by ASA in a dose-dependent manner and remains relatively constant over time once maximal inhibition has occurred, and (3) granule secretion by platelets during induced aggregation is inhibited by aspirin acutely but this effect does not persist during chronic administration at high doses.

• Study Type: Interventional
• Enrollment (Actual): 51
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37232-6602
      • Vanderbilt University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Males
• Age 18-40 years
• Non-smokers

Exclusion Criteria:

• ASA/NSAID use previous 14 days.
• Evidence of ASA/NSAID use within previous 14 days at baseline visit based on investigator interpretation of platelet aggregation and platelet secretion studies.
• History of chronic NSAID use.
• Currently taking NSAIDs, corticosteroids, or anticoagulants.
• History of coronary artery disease, myocardial infarction, coronary artery bypass grafting, percutaneous angioplasty, diabetes mellitus or stroke.
• 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 reaction to ASA.
• Initial platelet count <100K/µl or >500K/µl.
• Initial hematocrit <35% or >50%.
• Weight less than 110 pounds.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; ASA 40mg daily for 8 weeks followed by 3 weeks of observation	Drug: aspirin; 40mg aspirin: one 40-mg aspirin capsule by mouth each morning + one Avicel capsule by mouth each evening; Other Names: ASA; acetylsalicylic acid; Drug: aspirin; 1300mg aspirin: one 650-mg capsule by mouth twice daily; Other Names: ASA; acetylsalicylic acid
Experimental: 2; ASA 1300mg daily for 8 weeks followed by 3 weeks of observation	Drug: aspirin; 40mg aspirin: one 40-mg aspirin capsule by mouth each morning + one Avicel capsule by mouth each evening; Other Names: ASA; acetylsalicylic acid; Drug: aspirin; 1300mg aspirin: one 650-mg capsule by mouth twice daily; Other Names: ASA; acetylsalicylic acid
Placebo Comparator: 3; Placebo: one Avicel (cellulose) capsule by mouth twice daily	Drug: placebo; Placebo: one Avicel (cellulose) capsule by mouth twice daily; Other Names: Avicel; cellulose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Comparison of platelet aggregation, serum thromboxane B2 (TxB2) levels, urinary thromboxane metabolite (Tx-M) levels, and urinary prostacyclin metabolite (PGI-M) levels over time and across dose ranges.	11 weeks

Collaborators and Investigators

• Sponsor: Vanderbilt University
• Investigators: Principal Investigator: John A Oates, M.D., Vanderbilt University

Study record dates

Study Major Dates

• Study Start: June 1, 2004
• Primary Completion (Actual): February 1, 2011
• Study Completion (Actual): February 1, 2011

Study Registration Dates

• First Submitted: September 5, 2008
• First Submitted That Met QC Criteria: September 5, 2008
• First Posted (Estimate): September 8, 2008

Study Record Updates

• Last Update Posted (Actual): April 12, 2017
• Last Update Submitted That Met QC Criteria: April 10, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Keywords: platelet aggregation; granule secretion; thromboxane production; prostacyclin production
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Aspirin
• Other Study ID Numbers: GM15431-JAO1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No