The Effects of Aspirin and Acetaminophen on the Stomach in Healthy Volunteers
Information source: University of Illinois
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Healthy
Intervention: Acetaminophen - 4 grams per day + Placebo (Drug); Aspirin - 325 mg per day + Placebo (Drug); Acetaminophen 4 gram per day + Aspirin 325 mg per day (Drug)
Phase: Phase 4
Sponsored by: University of Illinois
Official(s) and/or principal investigator(s):
Jay L Goldstein, MD, Principal Investigator, Affiliation: University of Illinois
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.
Official title: Does Acetaminophen Potentiate the Gastroduodenal Mucosal Injury of Aspirin? A Prospective, Randomized, Pilot Study.
Study design: Treatment, Randomized, Double Blind (Subject, Investigator, Outcomes Assessor), Active Control, Single Group Assignment, Pharmacodynamics Study
Primary outcome: 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.
Secondary outcome: 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.
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.
Minimum age: 18 Years.
Maximum age: 75 Years.
1. Be a cooperative, healthy male or female between the ages of 18-75 inclusive.
2. Have a physical examination which reveals no clinically significant abnormalities at
the screening visit.
3. Have fewer than 6 gastric or duodenal erosions visible on nasal endoscopy at Visit 2.
4. 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
5. Have provided written informed consent prior for admission to this study.
6. H. pylori negative serologic exam prior to baseline nasal EGD.
1. Active GI disease (e. g. IBD), or a history of GI ulcers or bleeding
2. History of gastric or intestinal surgery
3. Use of ASA, NSAIDs, coxibs, or acetaminophen at any dose within 2 weeks prior to the
randomization visit of the study.
4. Positive FOBT at baseline.
5. 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
6. A known allergy to the topical anesthetic, lidocaine.
Locations and Contacts
University of Illinois Medical Center, Chicago, Illinois 60612, United States
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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.
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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.
Starting date: December 2006
Ending date: November 2007
Last updated: January 4, 2008