A randomized noninferiority trial comparing tegoprazan triple therapy and bismuth quadruple therapy for Helicobacter pylori eradication

Abstract

Abstract Rising antibiotic resistance has compromised the efficacy of standard Helicobacter pylori ( H. pylori ) eradication regimens. This multicenter trial aimed to evaluate whether a simplified tegoprazan-based triple therapy (TAD) is non-inferior to tegoprazan-based bismuth quadruple therapy (TADB) in a high-resistance setting. In this randomized, open-label, non-inferiority trial conducted across nine centers in China, 274 treatment-naïve patients were randomized (1:1) to receive either Group TAD (tegoprazan 50 mg, amoxicillin 1000 mg, doxycycline 100 mg) or Group TADB (TAD plus bismuth potassium citrate 600 mg) twice daily for 14 days. In the per-protocol (PP) analysis, eradication rates were 91.7% (111/121) for Group TAD and 96.0% (120/125) for Group TADB. Using the Newcombe score method against a pre-specified non-inferiority margin of -10%, the difference in per-protocol eradication rates was − 4.3% (95% CI: -9.8% to 2.0%), successfully establishing statistical non-inferiority. Intention-to-treat (ITT) analysis yielded consistent results (83.5% vs. 85.1%, P = 0.835). Group TAD demonstrated a significantly superior safety profile (22.6% vs. 46.1% AEs, P < 0.001). A simplified tegoprazan-based triple therapy is non-inferior to its bismuth-containing counterpart, offering high efficacy with a significantly improved safety profile and reduced pill burden. Chinese Clinical Trial Registry, ChiCTR2500102215. Registered 2025-05-12 (Retrospectively registered).