Comparative effectiveness and safety of vonoprazan/amoxicillin-based dual therapy versus quadruple therapy as second-line treatment for Helicobacter pylori Infection: a retrospective cohort study

The introduction of vonoprazan has markedly enhanced the effectiveness of the first-line Helicobacter pylori (H. pylori) eradication regimens. This study aimed to compare the effectiveness of vonoprazan-amoxicillin based dual therapy with that of quadruple therapy as second-line treatments, while also investigating potential clinical predictors of therapeutic success. From January 2023 to June 2025, we retrospectively analyzed clinical data from H. pylori-infected patients who received second-line treatment with either: vonoprazan-amoxicillin dual therapy (VA) or VA based quadruple therapy (VAMB; vonoprazan, amoxicillin, minocycline, and colloidal bismuth pectin). The eradication status was evaluated by ^13/14C-urease breath test four weeks after treatment completion. Adverse events and medication compliance were systematically documented during follow-up. The study included 241 patients, with 107 receiving VA dual therapy and 134 undergoing VAMB quadruple therapy. Eradication rates were comparable between groups: 90.7% (VA) versus 92.5% (VAMB) by modified intention-to-treat (mITT) analysis, and 91.4% versus 93.7% by per-protocol (PP) analysis (all p > 0.05). Notably, the VA regimen demonstrated significantly fewer adverse events (8.4% vs 17.9%, p = 0.033). Both treatment arms maintained excellent medication adherence. Compared to the vonoprazan-amoxicillin-minocycline-bismuth (VAMB) quadruple regimen, vonoprazan-amoxicillin (VA) dual therapy achieved comparable eradication efficacy with a more favorable safety profile in second-line H. pylori treatment, representing a simplified yet effective rescue therapy option.