Comparative Analysis of High-Dose Dual Therapies in First-Line Helicobacter pylori Eradication: An Inverse Probability of Treatment-Weighted Multicenter Study

Abstract Background High-dose dual therapy (HDDT) is a promising first-line treatment option for Helicobacter pylori infection. In this study, we aimed to compare the efficacy and safety of different HDDT regimens. Methods This multicenter retrospective study included data from 10 centers between January 2022 and January 2025. Inverse probability of treatment-weighted (IPTW) adjustment was used to address the imbalance in variables across groups. The outcomes included the eradication rate, adverse events and adherence. Results A total of 1,665 patients were included, with a full analysis set (FAS) eradication rate of 88.6% and a per-protocol (PP) eradication rate of 89.5% for HDDT. After IPTW adjustment, the eradication rate of vonoprazan-amoxicillin (VA) 14-day based on FAS analysis was 95.1%, which was significantly higher than VA-10 day (88.7%) (P = 0.001), esomeprazole-amoxicillin (EA) (85.1%) (P < 0.001), and tegoprazan-amoxicillin (TA) (87.3%) (P < 0.001). The incidence of adverse events for VA-14 was 8.1%, which was comparable to VA-10 (11.1%) but lower than TA (14.4%) and EA (15.3%) (P = 0.002). Adherence showed no significant difference across groups. High body surface area (BSA) (≥1.80 m²) (OR 1.594, 95% confidence interval [CI], 1.018-2.495, P = 0.041), poor adherence (OR 4.975, 95% CI, 2.753-8.992, P < 0.001), and non-VA-14 treatment regimen were independent risk factors for eradication failure. Factors varied across regimens. Conclusions HDDT, particularly VA-14, is a competitive first-line option for H. pylori eradication. High BSA and low adherence were risk factors for eradication failure but varied across regimens, highlighting the necessity of personalized adjustment.