The Effects of Aspirin and Acetaminophen on the Stomach in Healthy Volunteers - Full Text View

Sponsor:	University of Illinois
Information provided by:	University of Illinois
ClinicalTrials.gov Identifier:	NCT00594867

Purpose

Aspirin is a medication commonly used to relieve minor pains. Aspirin has also been used to prevent heart attacks and strokes. Aspirin, however, can also cause damage to the stomach and/or intestinal lining leading to the development of erosions ("small sores") and/or ulcers ("large sores"). Erosions may cause bleeding ("bleeding ulcers") and/or perforations ("holes in the stomach"). Acetaminophen, often referred by the brand name, Tylenol, is also used to treat minor pains but is not commonly recognized to cause damage to the stomach lining.

Many patients often take both of these medications together. While the effects on the stomach lining of each medication, when used alone, are known, the effects of both medications, when used together, are not.

The purpose of this study is to show whether or not the collective effects of both aspirin and acetaminophen, when used together, increase the damage on the stomach lining when compared to either medication alone.

Condition	Intervention	Phase
Healthy	Drug: Acetaminophen - 4 grams per day + Placebo Drug: Aspirin - 325 mg per day + Placebo Drug: Acetaminophen 4 gram per day + Aspirin 325 mg per day	Phase IV

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Investigator, Outcomes Assessor), Active Control, Single Group Assignment, Pharmacodynamics Study
Official Title:	Does Acetaminophen Potentiate the Gastroduodenal Mucosal Injury of Aspirin? A Prospective, Randomized, Pilot Study.

Resource links provided by NLM:

MedlinePlus related topics: Endoscopy

Drug Information available for: Acetylsalicylic acid Acetaminophen CT 2584

U.S. FDA Resources

Further study details as provided by University of Illinois:

Primary Outcome Measures:

Incidence of combined gastric and duodenal ulcers, defined as >1 gastric, pyloric channel or duodenal ulcer (score 7), as determined by nasal upper GI endoscopy on day 7 of treatment. [ Time Frame: 7 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Incidence of any gastric or duodenal ulcer (score 7) and any gastric and duodenal, gastric or duodenal erosions/ulcer (score 4-7) as determined by nasal upper endoscopy on day 7 of treatment. [ Time Frame: 7 days ] [ Designated as safety issue: No ]

Enrollment:	94
Study Start Date:	December 2006
Study Completion Date:	November 2007
Primary Completion Date:	December 2007 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Active Comparator Acetaminophen - 4 grams per day + Placebo	Drug: Acetaminophen - 4 grams per day + Placebo Acetaminophen - 4 grams per day + Placebo
2: Active Comparator Aspirin - 325 mg per day + Placebo	Drug: Aspirin - 325 mg per day + Placebo Aspirin - 325 mg per day + Placebo
3: Experimental Acetaminophen 4 gram per day + Aspirin 325 mg per day	Drug: Acetaminophen 4 gram per day + Aspirin 325 mg per day Acetaminophen 4 gram per day + Aspirin 325 mg per day

Detailed Description:

Low dose aspirin is used for the primary and secondary prevention of cardiovascular thromboembolic events. As a non-selective inhibitor of cyclooxygenase, aspirin use results in irreversible COX-1 inhibition leading to impaired platelet aggregation. However, aspirin also inhibits COX-1 activity in the gastric mucosa by suppressing the synthesis of protective prostaglandins. In doing so, this creates a state of propensity for the development of aspirin-associated gastrointestinal ulcers and ulcer complications.

A high proportion of aspirin users also require concomitant use of anti-inflammatory medications for the treatment of pain and arthritis. However, evidence suggests that the risk of developing gastroduodenal ulcers and ulcer complications is significantly increased when aspirin is co-administered with other nonselective NSAIDs. In a previous study, concomitant aspirin (325 mg daily) in healthy subjects taking naproxen (500mg bid) was associated with endoscopic ulcer rates of 27.3% as compared to aspirin alone (7.6%). In a separate and independent trial of similar design, patients using 81 mg of aspirin in conjunction with daily naproxen also resulted in a higher incidence of gastric and duodenal ulcers than aspirin therapy alone. Beyond endoscopic ulcer rates, the risk of upper gastrointestinal hemorrhage has been reported to be substantially increased with concurrent administration of low-dose aspirin with nonselective NSAIDS. These data suggest that the gastrointestinal toxicity of combined aspirin with other NSAIDs may be more than additive.

Eligibility

Ages Eligible for Study:	18 Years to 75 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

Be a cooperative, healthy male or female between the ages of 18-75 inclusive.
Have a physical examination which reveals no clinically significant abnormalities at the screening visit.
Have fewer than 6 gastric or duodenal erosions visible on nasal endoscopy at Visit 2.
If the subject is female and of childbearing potential, she has been using effective contraception since the last date of her menses, will continue to use effective contraception during the study period, is not breast-feeding or lactating at screening and has had a negative urine pregnancy test at screening. Women who have been post-menopausal for less than 2 years will also require a urine pregnancy test at screening.
Have provided written informed consent prior for admission to this study.
H. pylori negative serologic exam prior to baseline nasal EGD.

Exclusion Criteria:

Active GI disease (e.g. IBD), or a history of GI ulcers or bleeding
History of gastric or intestinal surgery
Use of ASA, NSAIDs, coxibs, or acetaminophen at any dose within 2 weeks prior to the randomization visit of the study.
Positive FOBT at baseline.
Use of over-the-counter or prescription: sucralfate, antacids, H2-receptor antagonists, misoprostol, or proton pump inhibitors 4 weeks prior to enrollment and/or during the study
A known allergy to the topical anesthetic, lidocaine.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00594867

Locations

United States, Illinois
University of Illinois Medical Center
Chicago, Illinois, United States, 60612

Sponsors and Collaborators

University of Illinois

Investigators

Principal Investigator:

Jay L Goldstein, MD

University of Illinois

More Information

Publications:

Antithrombotic Trialists' Collaboration. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ. 2002 Jan 12;324(7329):71-86. Erratum in: BMJ 2002 Jan 19;324(7330):141.

Patrono C, García Rodríguez LA, Landolfi R, Baigent C. Low-dose aspirin for the prevention of atherothrombosis. N Engl J Med. 2005 Dec 1;353(22):2373-83. Review. No abstract available.

Weil J, Colin-Jones D, Langman M, Lawson D, Logan R, Murphy M, Rawlins M, Vessey M, Wainwright P. Prophylactic aspirin and risk of peptic ulcer bleeding. BMJ. 1995 Apr 1;310(6983):827-30.

Derry S, Loke YK. Risk of gastrointestinal haemorrhage with long term use of aspirin: meta-analysis. BMJ. 2000 Nov 11;321(7270):1183-7.

Goldstein JL, Lowry SC, Lanza FL, Schwartz HI, Dodge WE. The impact of low-dose aspirin on endoscopic gastric and duodenal ulcer rates in users of a non-selective non-steroidal anti-inflammatory drug or a cyclo-oxygenase-2-selective inhibitor. Aliment Pharmacol Ther. 2006 May 15;23(10):1489-98.

Sørensen HT, Mellemkjaer L, Blot WJ, Nielsen GL, Steffensen FH, McLaughlin JK, Olsen JH. Risk of upper gastrointestinal bleeding associated with use of low-dose aspirin. Am J Gastroenterol. 2000 Sep;95(9):2218-24.

Cryer B, Feldman M. Cyclooxygenase-1 and cyclooxygenase-2 selectivity of widely used nonsteroidal anti-inflammatory drugs. Am J Med. 1998 May;104(5):413-21.

Lanza FL, Codispoti JR, Nelson EB. An endoscopic comparison of gastroduodenal injury with over-the-counter doses of ketoprofen and acetaminophen. Am J Gastroenterol. 1998 Jul;93(7):1051-4.

Jick H. Effects of aspirin and acetaminophen in gastrointestinal hemorrhage. Results from the Boston Collaborative Drug Surveillance Program. Arch Intern Med. 1981 Feb 23;141(3 Spec No):316-21.

Responsible Party:	University of Illinois at Chicago ( Jay L. Goldstein )
Study ID Numbers:	ACETAASA
Study First Received:	January 4, 2008
Last Updated:	January 4, 2008
ClinicalTrials.gov Identifier:	NCT00594867 History of Changes
Health Authority:	United States: Institutional Review Board

Keywords provided by University of Illinois:

Healthy
Volunteer

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
Aspirin

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
Acetaminophen

ClinicalTrials.gov processed this record on November 09, 2009