Vonoprazan High-dose Dual, Vonoprazan Triple and Rabeprazole Reverse Hybrid Therapies for First-line Treatment of H. pylori Infection: A Multicenter Randomized Trial

OBJECTIVES:The study aimed to compare the efficacy of 14-day vonoprazan high-dose dual, vonoprazan triple and rabeprazaole reverse hybrid therapies for the first-line treatment of H. pylori infection.METHODS:In the multi-center, randomized, open-label trial, we consecutively recruited adult H. pylori-infected patients from six centers in Taiwan. Subjects were randomly assigned (1:1:1) to 14-day vonoprazan high-dose dual, vonoprazan triple or rabeprazole reverse hybrid therapy. Eradication status was determined by ¹³C-urea breath test. The primary outcome was the eradication rate of H. pylori assessed in the intention-to-treat population.RESULTS:Between December 2021 and April 2024, 906 patients were recruited. The eradication rates were 83.8% (253/302) for vonoprazan high-dose dual therapy, 90.1% (272/302) for vonoprazan triple therapy, and 89.1% (271/302) for rabeprazole reverse hybrid therapy in intention-to-treat analysis. Vonoprazan high-dose dual therapy was inferior to both vonoprazan triple (95% confidence interval: -11.5% to -1.1%; p=0.022) and rabeprazole reverse hybrid therapies (95% confidence interval: -10.7% to 0.1%; p=0.031). There were no significant differences in the overall proportions of patients experiencing adverse events among vonoprazan high-dose dual, vonoprazan triple, and rabeprazole reverse hybrid groups (10.3%, 15.2%, and 15.6%, respectively). Body weight ≥60 kg, clarithromycin resistance, and poor drug adherence were independent risk factors predicting eradication failure for the three corresponding therapies, with odds ratios of 3.2 (1.3-7.5), 4.8 (1.2-18.9), and 14.8 (2.8-78.8), respectively.CONCLUSION:Vonoprazan triple therapy and rabeprazole reverse hybrid therapy are preferable to vonoprazan dual therapy for first-line treatment of H. pylori infection.