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

Background: Antimicrobial resistance has decreased eradication rates for H. pylori worldwide. Objective: To determine if a sequential treatment regimen eradicates H. pylori better than standard triple drug therapy in adults with dyspepsia or peptic ulcer disease. Design: Randomized double-blind controlled trial. Setting: Two Italian Hospitals between September 2003 and April 2006. Patients: 300 patients with dyspepsia or peptic ulcer. Measurements: 13C urea breath test, upper endoscopy, histology, rapid urease test, bacterial culture, and antibiotic resistance assessment. Intervention: 300 patients randomized to a 10-day sequential regimen (pantoprazole 40 mg, amoxicillin 1 g and placebo, each administered twice daily for the first 5 days, followed by pantoprazole 40 mg, clarithromycin 500 mg and tinidazole 500 mg each twice daily for the remaining 5 days) or standard 10-day therapy (pantoprazole 40 mg, clarithromycin 500 mg, and amoxicillin 1 g; each administered twice a day). Results: The eradication rate achieved with the sequential regimen was statistically significantly greater than that obtained with the standard treatment for the intent to treat analysis: 89% vs. 77% (p=0.0134; difference 11%, 95% confidence interval: 3 to 20%); modified intent to treat: 91% vs 78% (P = 0.0022; difference 13%, 95% confidence interval: 5 to 21) and the per protocol analysis 93% vs. 79% (P = 0.0010; difference 14% confidence interval 6 to 21). The sequential therapy was statistically 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). There was 1 discontinuation (0.7%) due to side-effects in the standard therapy group.