Sex-Specific Efficacy and Safety of Potassium-Competitive Acid Blocker–Bismuth Quadruple Therapy for Second-Line Helicobacter pylori Eradication: An Open-Label Randomized Controlled Trial

Objectives: Sex differences may influence the efficacy, safety, and adherence to Helicobacter pylori (H.pylori) eradication therapy.This study compared the efficacy and safety of potassium-competitive acid blocker (P-CAB)-bismuth-containing moxifloxacin quadruple therapy and conventional proton pump inhibitor (PPI)-based moxifloxacin triple therapy as second-line treatment for H. pylori, with particular attention to sexspecific outcomes.Methods: In this prospective, single-center, open-label study, subjects with persistent H. pylori infection after first-line treatment failure received either a 14-day PPI-based moxifloxacin triple regimen (esomeprazole, amoxicillin, and moxifloxacin) or a 14-day P-CAB-bismuth-containing moxifloxacin quadruple regimen (tegoprazan, amoxicillin, moxifloxacin, and bismuth).Eradication efficacy, drug compliance, and adverse events were evaluated.Findings: A total of 141 patients (40 males and 101 females) were included, comprising 72 patients in the study group and 69 in the conventional group.In the intention-totreat analysis, eradication rates were 65.3% (47/72) and 59.4% (41/69), respectively (p=0.492).In the per-protocol analysis, eradication rates were 78.3% (47/60) and 77.4% (41/53), respectively (p=0.901).In males, ITT and PP eradication rates were 75.0% and 83.3% in the study group and 55.0% and 73.3% in the conventional group, respectively.Among females, the corresponding rates were 61.5% and 76.2% versus 61.2% and 78.9%.Adverse events tended to be more frequent in females, although the difference was not statistically significant.Dropout rates did not differ significantly by sex or treatment group.Conclusions: No statistically significant differences in efficacy or safety were detected between P-CAB-bismuth-containing moxifloxacin quadruple therapy and conventional PPI-based moxifloxacin triple therapy as second-line treatment for H. pylori.Despite similar eradication rates between sexes, the higher frequency of adverse events in females warrants further large-scale studies on sex-specific treatment safety and adherence.Trial registration: Retrospective registration submitted to ClinicalTrials.