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

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 1665 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 = .001), esomeprazole-amoxicillin (EA) (85.1%) (P < .001), and tegoprazan-amoxicillin (TA) (87.3%) (P < .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 = .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 = .041), poor adherence (OR 4.975, 95% CI, 2.753-8.992, P < .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.