The Effects of Aspirin and Acetaminophen on the Stomach in Healthy Volunteers

This study has been completed.
Sponsor:
Information provided by:
University of Illinois at Chicago
ClinicalTrials.gov Identifier:
NCT00594867
First received: January 4, 2008
Last updated: NA
Last verified: December 2007
History: No changes posted
  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 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Does Acetaminophen Potentiate the Gastroduodenal Mucosal Injury of Aspirin? A Prospective, Randomized, Pilot Study.

Resource links provided by NLM:


Further study details as provided by University of Illinois at Chicago:

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

  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 screening.
  5. Have provided written informed consent prior for admission to this study.
  6. H. pylori negative serologic exam prior to baseline nasal EGD.

Exclusion Criteria:

  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.
  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: NCT00594867

Locations
United States, Illinois
University of Illinois Medical Center
Chicago, Illinois, United States, 60612
Sponsors and Collaborators
University of Illinois at Chicago
Investigators
Principal Investigator: Jay L Goldstein, MD University of Illinois at Chicago
  More Information

Publications:

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

Keywords provided by University of Illinois at Chicago:
Healthy
Volunteer

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

ClinicalTrials.gov processed this record on October 23, 2014