Triple versus dual therapy for eradicating Helicobacter pylori and preventing ulcer recurrence: a randomized, double-blind, multicenter study of lansoprazole, clarithromycin, and/or amoxicillin in different dosing regimens.
OBJECTIVE: The efficacy and safety of dual and triple therapies with a proton pump inhibitor and antibiotic(s) for therapy of Helicobacter pylori-associated duodenal ulcer disease have been compared using results from independent studies using different methods and regimens, making interpretation difficult. In a large, double-blind, multicenter study conducted in the United States, we compared a triple therapy regimen with four dual therapy and one monotherapy regimens in the eradication of H. pylori and the prevention of ulcer recurrence. METHODS: Patients with active duodenal ulcer disease or history of duodenal ulcer disease within the past year and H. pylori infection were randomized to receive one of six 14-day treatment regimens: lansoprazole 30 mg, clarithromycin 500 mg, and amoxicillin 1 gm b.i.d.; lansoprazole 30 mg b.id. and either clarithromycin 500 mg b.i.d. or t.i.d.; lansoprazole 30 mg b.i.d. or t.i.d. with amoxicillin 1 gm t.i.d.; or lansoprazole 30 mg t.i.d. alone. No additional acid suppression therapy followed eradication therapy. Primary efficacy endpoints were eradication of H. pylori and ulcer recurrence. RESULTS: Of 396 patients enrolled in the study, 352 met the entry criteria for duodenal ulcer status and H. pylori positivity. At 4-6 wk after the end of therapy, H. pylori was eradicated from 94% (44 of 47) of patients receiving lansoprazole, clarithromycin, and amoxicillin triple therapy, 77% (39 of 51) of those receiving lansoprazole t.i.d./amoxicillin t.i.d., 75% (36 of 48) of those receiving lansoprazole b.i.d./clarithromycin t.i.d., 57% (28 of 49) of those receiving lansoprazole b.i.d./clarithromycin b.i.d., 53% (26 of 49) of those receiving lansoprazole b.i.d./amoxicillin t.i.d., and 2% (1 of 53) of those receiving lansoprazole monotherapy (p < or = 0.05, triple therapy vs each dual therapy and each dual therapy vs monotherapy). Of those patients who were documented as free of ulcer at 4-6 wk after treatment, ulcers recurred within 6 months in 7% of patients receiving triple therapy, as compared with 13-23% of patients receiving dual therapy, and 69% of patients receiving lansoprazole monotherapy. Patients who were H. pylori negative at 4-6 wk after treatment were less likely to have an ulcer recurrence than were patients who were H. pylori positive (11% [10 of 95] vs 47% [20 of 43], respectively, across treatment groups). For triple therapy and dual therapy, a similar proportion of patients reported a drug-related adverse event (23% vs 17-33%, respectively). CONCLUSIONS: In patients with active or a recent history of duodenal ulcer, a 14-day course of lansoprazole-based triple therapy without additional acid suppression therapy is highly effective in the eradication of H. pylori and in preventing ulcer recurrence. Among the dual therapies, higher eradication rates occurred when lansoprazole (with amoxicillin) or clarithromycin (with lansoprazole) was administered t.i.d. vs b.i.d., but the rates were still significantly lower than with lansoprazole triple therapy with all three drugs administered b.i.d.