Loss of Effect of Aspirin on Platelet Aggregation During Chronic Administration - Full Text View

Sponsored by:	Vanderbilt University
Information provided by:	Vanderbilt University
ClinicalTrials.gov Identifier:	NCT00748371

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 IV

Drug Information available for: Cellulose Cellulose sodium phosphate Phosphocellulose Acetylsalicylic acid Epoprostenol Epoprostenol sodium

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Basic Science, Randomized, Double Blind (Subject, Investigator), Placebo Control, Parallel Assignment, Pharmacodynamics Study
Official Title:	Loss of Effect of Aspirin on Platelet Aggregation During Chronic Administration

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
1: Experimental 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
2: Experimental ASA 1300mg daily for 8 weeks followed by 3 weeks of observation	Drug: aspirin 1300mg aspirin: one 650-mg capsule by mouth twice daily
3: Placebo Comparator Placebo: one Avicel (cellulose) capsule by mouth twice daily	Drug: placebo Placebo: one Avicel (cellulose) capsule by mouth twice daily

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

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

Contacts

Contact: Denise Oram, R.N.	615-343-4847	denise.oram@vanderbilt.edu
Contact: John A Oates, M.D.	615-343-4847	john.oates@vanderbilt.edu

Locations

United States, Tennessee
Vanderbilt University	Recruiting
Nashville, Tennessee, United States, 37232-6602
Principal Investigator: John A Oates, M.D.
Sub-Investigator: David H Adler, M.D.
Sub-Investigator: Olivier Boutaud, Ph.D.
Sub-Investigator: Alyssa Browning, M.D.
Sub-Investigator: James P Smith, M.D.

Sponsors and Collaborators

Vanderbilt University

Investigators

Principal Investigator:

John A Oates, M.D.

Vanderbilt University

More Information

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

Keywords provided by Vanderbilt University:

platelet aggregation
granule secretion
thromboxane production
prostacyclin production

Study placed in the following topic categories:

Aspirin
Epoprostenol

Additional relevant MeSH terms:

Anti-Inflammatory Agents
Molecular Mechanisms of Pharmacological Action
Cyclooxygenase Inhibitors
Hematologic Agents
Physiological Effects of Drugs
Enzyme Inhibitors
Fibrinolytic Agents
Cardiovascular Agents
Pharmacologic Actions
Fibrin Modulating Agents

Analgesics, Non-Narcotic
Sensory System Agents
Therapeutic Uses
Platelet Aggregation Inhibitors
Anti-Inflammatory Agents, Non-Steroidal
Analgesics
Peripheral Nervous System Agents
Antirheumatic Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on January 14, 2009