Efficacy and Safety of Fexuprazan-Based Modified High-Dose Dual Therapy for Helicobacter pylori Eradication: A Randomized Clinical Trial

Abstract

Background/Aims The eradication efficacy of proton pump inhibitor (PPI)-based standard triple therapy (STT) for Helicobacter pylori infection has declined in Korea, largely because of increasing clarithromycin resistance. High-dose dual therapy (HDDT) using potent acid suppression represents a promising clarithromycin-sparing strategy. This study evaluated the efficacy and safety of fexuprazan-based modified HDDT (m-HDDT) including bismuth, compared with conventional PPI-based STT as first-line eradication therapy.Methods This prospective, multicenter, randomized, open-label, non-inferiority trial was conducted at eight tertiary hospitals in Korea. Treatment-na & iuml;ve adults with confirmed H. pylori infection were randomized to receive either m-HDDT (fexuprazan 40 mg twice daily, amoxicillin 1000 mg three times daily, and bismuth subcitrate potassium 300 mg three times daily) or STT (lansoprazole 30 mg, amoxicillin 1000 mg, and clarithromycin 500 mg, all twice daily) for 14 days. Eradication was assessed by urea breath test 4-8 weeks after therapy. The primary endpoint was the eradication rate in the full analysis set (FAS), with a prespecified non-inferiority margin of -10%. Safety and compliance were evaluated as secondary outcomes.Results In total, 196 patients were included in the FAS (m-HDDT, n = 96; STT, n = 100). Helicobacter pylori eradication was achieved in 81.3% of patients in the m-HDDT group and 79.0% in the STT group, demonstrating non-inferiority of m-HDDT (one-sided Wald test, p = 0.0158). Per-protocol analysis yielded consistent results (p = 0.0215). Drug compliance was high in both groups, with mean compliance rates of 97.0% in the m-HDDT group and 99.0% in the STT group; more than 95% of patients in each group achieved >= 80% compliance. The incidence of treatment-emergent adverse events was comparable between groups (16.7% vs. 14.0%); most events consisted of mild gastrointestinal symptoms. No serious adverse events or treatment discontinuations due to adverse events were observed in either group.Conclusions Fexuprazan-based m-HDDT with bismuth was non-inferior to PPI-based STT for H. pylori eradication and demonstrated comparable safety and excellent compliance. This clarithromycin-sparing regimen can be considered an alternative treatment option in regions with high macrolide resistance.