Rabeprazole Protection of Aspirin Induced Gastric Damage.
Condition: Normal Subjects
Study type: Interventional
Phase: Phase 4

Summary: 
      To determine the effectiveness of rabeprazole in preventing or decreasing acute
      gastroduodenal injury caused by therapeutic doses of aspirin in a placebo-controlled,
      randomized, double-blind parallel group study.
    

Detailed description: 
      Thirty (30) eligible normal subjects will be randomized to one of two study groups:
      rabeprazole 20 mg OD (n=15) or placebo OD (n=15). Both rabeprazole and identically appearing
      placebo will be given to Temple from Janssen Pharmaceuticals. The randomization schedule will
      be prepared by John Gaughan, PhD of Temple University School of Medicine Department of
      Biostatistics using a random number generator. The coded medications will be dispensed by
      Temple's Department of Pharmacy. Study subjects and the investigators will be blinded as to
      the subject receiving either placebo or rabeprazole. The sealed code will not be broken until
      after the data analysis.

      Study subjects will be admitted to the Temple Clinical Research Center for the duration of
      the study. Appendix I has the study time line. Study subjects will arrive at the CRC at 6:00
      A.M. on study day 1. Female subjects will have a urine pregnancy test performed. Blood tests
      will be obtained for salicylate and alcohol levels. Each study subject will receive a single
      dose of study drug (rabeprazole or placebo) at 7:00 A.M. on study days 1, 2 and 3-one hour
      before breakfast on days 1 and 3 and 90 minutes before breakfast on study day 2. All research
      subjects will receive aspirin (ASA), 325 mg tablets as 2 tablets with 8 oz. water every 4
      hours at 8:30 A.M., 12:30 P.M., 4:30 P.M., 8:30 P.M., 12:30 A.M. and 4:30 A.M. daily for
      study days 1, 2 and 3 (a total of 3900 mg aspirin per day). Esophagogastroduodenoscopy will
      be performed at 8:00 A.M. on the mornings of days 2 and 4; that is, 24 hours and 72 hours
      after initiation of aspirin and test drug. During each endoscopy, the maximum number of
      submucosal hemorrhages and erosions in an endoscopic field from the anterior and posterior
      walls of the antrum will be counted. In addition, a Lanza score will be assigned for each
      endoscopic examination (Appendix II). Endoscopic photographs will be obtained for each
      endoscopic examination. A blood sample will be obtained at 7:00 A.M. on study days 2, 3 and 4
      for measurement of hemoglobin and serum salicylate. Meals will be standardized as follows for
      each day of the study:

      Breakfast: 8:00 A.M. (study days 1 and 3); 8:30 A.M. (study day 2) 2 eggs, 2 slices of soft
      white bread, 4 oz unsweetened orange juice Lunch: 1:00 P.M. (study days 1, 2 and 3) Turkey
      sandwich, 2 slices of wheat bread, lettuce, tomato, 1 orange, 8 oz apple juice Dinner: 6:00
      P.M. (study days 1, 2 and 3) Two plain hamburgers, ketchup, mustard, lettuce and tomato;
      tossed green salad with thousand island dressing, 1 cup of French fries, 8 oz whole milk
      Snack: 10:00 P.M. (study days 1, 2 and 3) 4 graham crackers, 4 oz orange juice

      If the Lanza score reaches 4 for any subject indicating widespread involvement of the stomach
      with submucosal hemorrhages, erosions, or ulcerations, that subject will not receive any more
      aspirin, but continue with study drug of placebo or rabeprazole. If this was detected on day
      2 of the study, the subject will continue to receive the study drug with the repeat study
      endoscopy on day 4. If the Lanza score day 4 (the end of the study) is 4, the subject will be
      treated with rabeprazole 20 mg po qd for one month. If there was an ulcer, a repeat upper
      endoscopy will then be performed at 4 weeks to ensure healing.
    

Intervention name(s): Rabeprazole
Intervention type(s): Drug
Intervention MeSH terms: Rabeprazole
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double
Primary purpose: Prevention
Keywords: Rabeprazole; Nonsteroidal Antiinflammatory Drugs; Gastric erosions