Vonoprazan-based dual therapy with amoxicillin or doxycycline versus bismuth-containing quadruple therapy for Helicobacter pylori eradication: a prospective, multicenter, open-label, randomized controlled trial

Background Bismuth-containing quadruple therapy, the standard Helicobacter pylori ( H. pylori ) eradication regimen, is limited by adverse events and rising resistance. Vonoprazan-amoxicillin dual therapy offers simplicity but has mostly been tested using high-dose amoxicillin. Data on doxycycline in this context are scarce, and vonoprazan-doxycycline dual therapy remains unexplored. Methods A total of 579 H. pylori -positive patients were enrolled and randomly assigned in a 1:1:1 ratio to one of three 14-day treatment groups: the VBQ group (vonoprazan 20 mg, amoxicillin 1000 mg, doxycycline 100 mg, and colloidal bismuth pectin 300 mg, all twice daily); the VA group (vonoprazan 20 mg and amoxicillin 1000 mg, twice daily); and the VD group (vonoprazan 20 mg and doxycycline 100 mg, twice daily). A 13 C-urea breath test (UBT) was performed at least four weeks after treatment completion. H. pylori eradication rates, the incidence of adverse events during treatment, and medication adherence were compared among the three groups. Results In the intention-to-treat (ITT), modified intention-to-treat (mITT), and per-protocol (PP) analyses, the VA regimen demonstrated non-inferiority to the VBQ regimen. The VD regimen did not meet the non-inferiority criterion in the ITT analysis (79.3% vs. 83.4%, P = 0.070 for non-inferiority), but it demonstrated non-inferiority to the VBQ regimen in both the mITT (87.4% vs. 90.4%, P = 0.018) and PP (87.7% vs. 90.1%, P = 0.012) analyses. The overall incidence of adverse events was not significantly different between the VBQ and VA groups (P = 0.313), but it was significantly lower in the VD group compared to the VBQ group (P = 0.002). No statistically significant differences in medication adherence were observed between the VBQ group and either the VA (P = 0.381) or VD (P = 0.269) group. Conclusion Vonoprazan-low-dose amoxicillin dual therapy is a safe and simple alternative to bismuth containing quadruple therapy. Vonoprazan-doxycycline dual therapy demonstrates acceptable efficacy and may be considered for patients allergic to amoxicillin. Both align with antimicrobial stewardship principles of regimen simplification.