Efficacy and Safety of Vonoprazan and High-Dose Amoxicillin Dual Therapy for Rescue Treatment of Helicobacter pylori Infection: A Multicenter Randomized Controlled Trial

Abstract

Background: Vonoprazan and amoxicillin dual therapy has demonstrated favorable efficacy in the initial treatment of Helicobacter pylori (H. pylori) infection. This study aimed to evaluate the efficacy and safety of vonoprazan and high-dose amoxicillin (VHA) dual therapy for H. pylori rescue treatment. Methods: This was an open label, multicenter, non-inferiority, and randomized controlled clinical trial conducted at four institutions in both central and northwestern China. A total of 688 H. pylori-infected patients who had failed previous treatments were randomly assigned (1:1) to receive either VHA dual therapy or the tetracycline- and furazolidone-based bismuth-containing quadruple therapy (TFEB) for 14 days. Eradication rates, adverse event (AE) rates, and the patient compliance were compared between the two groups. Results: The eradication rates in the VHA and TFEB groups were 73.8% and 76.2% (p = 0.481), respectively, by intention-to-treat (ITT) analysis; 81.9% and 85.6% (p = 0.215), respectively, by modified ITT (MITT) analysis; and 82.1% and 85.6% (p = 0.248), respectively, by per-protocol (PP) analysis. VHA therapy remained non-inferior to TFEB in ITT, MITT, and PP analyses. The overall AE incidence in the VHA group was significantly lower compared with that in the TFEB group (13.4% vs. 28.5%, p < 0.001). Patients' compliance was similar between the two groups. A history of multiple prior eradication failures was an independent risk factor (2 failures: OR = 0.566, p = 0.032; ≥ 3 failures: OR = 0.335, p < 0.001) reducing the efficacy of H. pylori rescue therapy. Conclusion: The 14-day VHA dual therapy was non-inferior to bismuth-containing quadruple therapy, with a lower incidence of adverse events and good compliance, and may represent an effective alternative for H.pylori rescue treatment. Trial Registration: This trial was registered at ClinicalTrials.gov (No. NCT06168084).