Sequential therapy versus Triple Therapy for Helicobacter pylori Eradication: a randomized trial

Background: Antimicrobial resistance has decreased eradication
rates for Helicobacter pylori infection worldwide. Objective: To determine whether sequential treatment eradicates H. pylori infection better than standard triple-drug therapy for adults with dyspepsia or peptic ulcers. Design: Randomized, double-blind, placebo-controlled trial. Setting: Two Italian hospitals between September 2003 and April 2006. Patients: 300 patients with dyspepsia or peptic ulcers. Measurements: 13C-urea breath test, upper endoscopy, histologic evaluation, rapid urease test, bacterial culture, and assessment of antibiotic resistance.
Intervention: A 10-day sequential regimen (40 mg of pantoprazole, 1 g of amoxicillin, and placebo, each administered twice daily for the first 5 days, followed by 40 mg of pantoprazole, 500 mg of clarithromycin, and 500 mg of tinidazole, each administered twice daily for the remaining 5 days) or standard 10-day therapy (40 mg of pantoprazole, 500 mg of clarithromycin, and 1 g of amoxicillin, each administered twice daily).Results: The eradication rate achieved with the sequential regimen was significantly greater than that obtained with the standard treatment in the intention-to-treat analysis (89% vs. 77%; P 0.0134;difference, 12% [95% CI, 3% to 20%]), the modified intentionto-treat analysis (91% vs. 78%; P<0.0022; difference, 13% [CI,5% to 21%]), and the per-protocol analysis (93% vs. 79%; P <0.0013; difference, 14% [CI, 6% to 21%]). Sequential therapy was significantly more effective in patients with clarithromycin-resistant strains (89% vs. 29%; P 0.0034). The incidence of major and minor side effects did not differ between therapy groups (17% in both groups). One patient (0.7%) in the standard therapy group discontinued treatment because of side effects. Conclusions: Sequential therapy is statistically significant compared with standard therapy for eradicating H. pylori infection and is statistically significantly more effective in patients with clarithromycin-resistant strains. Side effects are similar with both treatment regimens and are rarely severe enough to cause discontinuation of therapy.