BACKGROUND & AIMS: The efficacy of treatment of Helicobacter pylori infection has decreased steadily because of increasing resistance to clarithromycin, metronidazole, and levofloxacin. Resistance to amoxicillin is generally low, and high intragastric pH increases the efficacy of amoxicillin, so we investigated whether a combination of a high-dose proton pump inhibitor and amoxicillin (dual therapy) was more effective than standard first-line or rescue therapies in eradicating H pylori.

METHODS

We performed a large-scale multihospital trial to compare the efficacy of a high-dose dual therapy (HDDT) with that of standard therapies in treatment-naive (n = 450) or treatment-experienced (n = 168) patients with H pylori infection. Treatment-naive patients were randomly assigned to groups given HDDT (rabeprazole 20 mg and amoxicillin 750 mg, 4 times/day for 14 days, group A1), sequential therapy for 10 days (group B1), or clarithromycin-containing triple therapy for 7 days (group C1). Treatment-experienced patients were randomly assigned to groups given HDDT for 14 days (group A2), sequential therapy for 10 days (B2), or levofloxacin-containing triple therapy for 7 days (C2). H pylori infection was detected by using the (13)C-urea breath test. We evaluated factors associated with treatment outcomes.

RESULTS

In the intention-to-treat analysis, H pylori was eradicated in 95.3% of patients in group A1 (95% confidence interval [CI], 91.9%-98.8%), 85.3% in B1 (95% CI, 79.6%-91.1%), and 80.7% in group C1 (95% CI, 74.3%-87.1%). Infection was eradicated in 89.3% of patients in group A2 (95% CI, 80.9%-97.6%), 51.8% in group B2 (95% CI, 38.3%-65.3%), and 78.6% (95% CI, 67.5%-89.7%) in group C2. The efficacy of HDDT was significantly higher than that of currently recommended regimens, irrespective of CYP2C19 genotype. Bacterial resistance to drugs was associated with treatment failure. There were no significant differences between groups in adverse events or patient adherence.

CONCLUSIONS

HDDT is superior to standard regimens as empirical first-line or rescue therapy for H pylori infection, with similar safety profiles and tolerability. ClinicalTrials.gov number: NCT01163435.