A double-blind study of prophylactic effect of misoprostol on lesions of gastric and duodenal mucosa induced by oral administration of tolmetin in healthy subjects.

Tolmetin, a nonsteroidal antiinflammatory drug, is known to induce edema, submucosal hemorrhage, and erosions of the gastrointestinal tract when administered at recommended doses. The purpose of our study was to determine whether misoprostol prevented or reduced the severity of duodenal and gastric mucosal injury induced by tolmetin. Following endoscopic screening, 60 healthy male and female subjects were assigned at random to one of two treatment groups. One group was treated with tolmetin (2000 mg/day, in four divided doses) and misoprostol (200 micrograms four times daily); the other with tolmetin and placebo. Both drugs were administered for six and a quarter days. On the seventh day, 2 hr after the last dose, an endoscopic examination of the gastric and duodenal mucosa was repeated, and the results graded. Subjects with 10 or fewer hemorrhages or erosions were considered treatment successes; those with 11 or more erosions, plus any other lesions, were considered treatment failures. A total of 59 subjects completed the study. One withdrew because of an unsuspected pregnancy. In regard to the gastric mucosa, seven of 29 (24%) placebo subjects were considered treatment successes. In the misoprostol group, 27 of 30 (90%) were treatment successes. This difference is statistically significant at the P less than 0.0001 level. The overall damage to the duodenal mucosa caused by tolmetin is less than that to the gastric mucosa, with the misoprostol-treated subjects having significantly less damage than the placebo subjects (P less than 0.001). Side effects were common in both groups, but almost all were mild, gastrointestinal in origin, and did not require treatment or withdrawal from the study.(ABSTRACT TRUNCATED AT 250 WORDS)

RCT Entities:   Population Interventions Outcomes