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

May 14, 2019 updated by: University of Illinois at Chicago

Does Acetaminophen Potentiate the Gastroduodenal Mucosal Injury of Aspirin? A Prospective, Randomized, Pilot Study.

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

94

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Single Group Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
7 days

Secondary Outcome Measures

Outcome Measure
Time Frame
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
7 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Illinois at Chicago

Investigators

  • Principal Investigator: Jay L Goldstein, MD, University of Illinois at Chicago

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2006

Primary Completion (Actual)

December 1, 2007

Study Completion (Actual)

December 1, 2007

Study Registration Dates

First Submitted

January 4, 2008

First Submitted That Met QC Criteria

January 4, 2008

First Posted (Estimate)

January 16, 2008

Study Record Updates

Last Update Posted (Actual)

May 15, 2019

Last Update Submitted That Met QC Criteria

May 14, 2019

Last Verified

May 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2006-0459

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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