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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Healthy

Intervention / Treatment
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* 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


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>Acetaminophen - 4 grams per day + Placebo | Drug: Acetaminophen - 4 grams per day + Placebo<br>* Acetaminophen - 4 grams per day + Placebo<br>|
| Active Comparator: 2<br>Aspirin - 325 mg per day + Placebo | Drug: Aspirin - 325 mg per day + Placebo<br>* Aspirin - 325 mg per day + Placebo<br>|
| Experimental: 3<br>Acetaminophen 4 gram per day + Aspirin 325 mg per day | Drug: Acetaminophen 4 gram per day + Aspirin 325 mg per day<br>* Acetaminophen 4 gram per day + Aspirin 325 mg per day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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. |  | 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | 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. |  | 7 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Healthy, Volunteer