Loss of Effect of Aspirin on Platelet Aggregation During Chronic Administration

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by:
Vanderbilt University
ClinicalTrials.gov Identifier:
NCT00748371
First received: September 5, 2008
Last updated: January 11, 2010
Last verified: January 2010
  Purpose

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.


Condition Intervention Phase
Platelet Aggregation
Drug: aspirin
Drug: placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Basic Science
Official Title: Loss of Effect of Aspirin on Platelet Aggregation During Chronic Administration

Resource links provided by NLM:


Further study details as provided by Vanderbilt University:

Primary Outcome Measures:
  • 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. [ Time Frame: 11 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 150
Study Start Date: June 2004
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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:
  • acetylsalicylic acid
  • ASA
Experimental: 2
ASA 1300mg daily for 8 weeks followed by 3 weeks of observation
Drug: aspirin
1300mg aspirin: one 650-mg capsule by mouth twice daily
Other Names:
  • acetylsalicylic acid
  • ASA
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00748371

Locations
United States, Tennessee
Vanderbilt University
Nashville, Tennessee, United States, 37232-6602
Sponsors and Collaborators
Vanderbilt University
Investigators
Principal Investigator: John A Oates, M.D. Vanderbilt University
  More Information

No publications provided

Responsible Party: John A. Oates, M.D., Vanderbilt University
ClinicalTrials.gov Identifier: NCT00748371     History of Changes
Other Study ID Numbers: GM15431-JAO1
Study First Received: September 5, 2008
Last Updated: January 11, 2010
Health Authority: United States: Institutional Review Board

Keywords provided by Vanderbilt University:
platelet aggregation
granule secretion
thromboxane production
prostacyclin production

Additional relevant MeSH terms:
Aspirin
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents
Hematologic Agents
Platelet Aggregation Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Antipyretics
Central Nervous System Agents

ClinicalTrials.gov processed this record on July 22, 2014