AbstractBackgroundAntibiotic resistance emerges as a major issue for Helicobacter pylori (H. pylori) treatment. High‐dose dual therapy has recently shown encouraging results in H. pylori eradication, but it has yet to be validated in this H. pylori highly infected area; it is also not known if this concept can be extended to antibiotics other than amoxicillin, and factors that affect the eradication. We investigate if rabeprazole plus amoxicillin or furazolidone regimens could be a first‐line therapy for H. pylori eradication, and factors that affect the curing rate.MethodsThis is a single‐center, prospective, open‐label, randomized‐controlled trial. Naive patients (n=292) were randomly treated with bismuth‐containing quadruple therapy (BQT), rabeprazole plus amoxicillin (RADT), or furazolidone (RFDT) groups. RADT and FADT use three times daily regimens. H. pylori diagnosis and eradication were determined and confirmed by ¹³C‐urea breath test.ResultsIn per‐protocol (PP) analysis, H. pylori eradication rate was 91.2% in BQT group, 89.6% in RADT, and 51.0% in RFDT group. In intention‐to‐treat (ITT) analysis, infection was eradicated in 86.7% of patients in BQT group, 85.8% in RADT, and 48.1% in RFDT groups, respectively. Noninferiority was confirmed between BQT and RADT groups. The incidence of side effects in BQT group was significantly higher than that in RADT group. Successful eradication was associated with lower body surface area (BSA) and low body mass index (BMI) in BQT group. Smoking and high BSA index reduced H. pylori eradication rate in RADT group.ConclusionsRabeprazole‐amoxicillin dual therapy is equally effective to the bismuth‐containing quadruple therapy for H. pylori eradication with fewer side effects and saves use of one antibiotic per each treatment. Successful eradication is also associated with low BSA and non‐smoking condition, which deserves future stratified analysis for refinement and optimization.