Lessons from the U.S. multicenter trial of ranitidine treatment for duodenal ulcer

In duodenal ulcer, acid and pepsin in greater amounts and at higher concentration enter the duodenum and specific treatment should be directed towards correcting this abnormality. Such treatment is provided by the histamine H2-receptor antagonists. We discuss the first U.S. multicenter trial of the new nitrofuran-based antagonist, ranitidine, in which 382 patients were treated for 4 weeks with either ranitidine 150mg b.i.d. (195 pts.) or placebo (187); both groups were allowed to use antacid for pain. Those treated with ranitidine had significantly less pain and used less antacids than the placebo-treated patients; after 2 weeks, 37% vs 19% were healed, and after 4 weeks, 73% vs 45% were healed (p less than 0.01). After 4 weeks, 124 unhealed patients were randomized to ranitidine vs placebo for another 4 weeks. Ranitidine treatment again produced a greater healing rate (p less than 0.01), regardless of prior treatment. The 3 subsets of the data which contained more than 34 patients were analyzed separately. Each showed 1 or more significant deviations (type I and type II errors) from the overall study, which was in all respects similar to the aggregate results of all similar studies overseas. We emphasize the need for studies of adequate size.