The Effects of Aspirin and Acetaminophen on the Stomach in Healthy Volunteers
Condition: Healthy
Study type: Interventional
Phase: Phase 4

Summary: 
      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.
    

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.
    

Intervention name(s): Acetaminophen - 4 grams per day + Placebo; Aspirin - 325 mg per day + Placebo; Acetaminophen 4 gram per day + Aspirin 325 mg per day
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Acetaminophen - 4 grams per day + Placebo; Aspirin - 325 mg per day + Placebo; Acetaminophen 4 gram per day + Aspirin 325 mg per day
Intervention MeSH terms: Aspirin; Acetaminophen
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Healthy; Volunteer