Double-blind comparison of two dosage regimens of misoprostol in the treatment of duodenal ulceration

Abstract

A multicenter double-blind study was conducted in 416 patients (306 male, 110 female) with active endoscopically proven duodenal ulcers who were randomly allocated to receive the prostaglandin E₁ methyl ester analog (Misoprostol/Cytotec), either in a dose of 400 Μg twice daily (206 patients) or 200 Μg four times daily (210 patients). No significant difference in the healing rates between the two groups was observed at four or eight weeks. In patients treated twice daily, the ulcer healing rate at four weeks for the intent-to-treat cohort was 124/205 (60.5%) and for the evaluable cohort was 96/136 (69.1%). In patients treated four times daily, the healing rate was 124/207 (59.9%) for the intent-to-treat cohort and 96/148 (64.9%) for the evaluable cohort. Similarly, the healing rates achieved at eight weeks for the twice- and the four-times-daily dosages in the intent-to-treat cohort were 72.2% and 74.4%, respectively, and for the evaluable cohort were 88.0% and 86.6%, respectively. Significantly more patients receiving misoprostol twice daily were free of ulcer pain after four weeks of treatment than were those receiving misoprostol four times daily, namely, 71.4% as compared with 57.9%, respectively (P=0.003) and for a median period of 21 as compared with 17 days (P=0.002). Diarrhea was more common in patients receiving the drug twice daily, (15.5%) than in those treated four times daily (5%) (P=0.001). Diarrhea, three or more stools daily, was often transient and self-limiting and only necessitated withdrawal from the trial in nine (4.4%) of those treated with misoprostol twice daily and in one patient (0.5%) of those treated four times daily. It is concluded that misoprostol is equally effective in healing duodenal ulcers whether given twice daily in doses of 400 Μg or four times daily in doses of 200 Μg. While a twice-daily dosage is more convenient for patients and encourages better compliance of therapy, it will induce, in around 5% of patients, unpleasant diarrhea which can be controlled, in most patients, by switching to a four-times-daily dosage in the knowledge that healing of the ulcer will not be impaired.