Efficacy of Three Amoxicillin Doses in Vonoprazan Dual Therapy for Helicobacter pylori Eradication: A Randomized Noninferiority Trial

BACKGROUND: Limited research has explored the efficacy of reduced amoxicillin dosages in vonoprazan-amoxicillin (VA) dual therapy for Helicobacter pylori eradication in China, and this study aimed to assess the noninferiority of these lower dosages compared to the standard high dose (3 g/d). METHODS: This was a noninferiority study with a -10% margin. H. pylori-positive patients from 13 centers in Jiangsu Province, China, were randomly assigned in a 1:1:1 ratio to receive a 14-day treatment, consisting of vonoprazan (20 mg BID) and high-dose amoxicillin (1 g TID, HVA), medium-dose amoxicillin (1 g BID, MVA), or low-dose amoxicillin (0.5 g TID, LVA). The eradication rates, adverse events (AEs), and medication adherence were compared. RESULTS: From January 13, 2023 to July 6, 2024, a total of 900 patients were enrolled. According to the intention-to-treat (ITT) and per-protocol (PP) analyses, the eradication rates for HVA, MVA, and LVA groups were 93.2% and 93.2%, 91.6% and 91.5%, and 87.0% and 86.8%, respectively. The efficacy of MVA was noninferior to HVA in ITT analysis (difference: -1.6%, 97.5% CI: -7.0% to 3.8%, p < 0.001) and PP analysis (difference: -1.7%, 97.5% CI: -7.1% to 3.7%, p < 0.001); LVA's effectiveness was less than HVA in ITT analysis (difference: -6.2%, 97.5% CI: -12.2% to -0.2%, p = 0.076) and PP analysis (difference:-6.4%, 97.5% CI: -12.4% to -0.3%, p = 0.089). The incidence of AEs and medication compliance among the three groups was similar. CONCLUSIONS: A 14-day VA regimen requires ≥ 2 g/d amoxicillin to maintain noninferior eradication efficacy versus 3 g/d, supporting dose reduction without compromising effectiveness. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05649540.