Comparison of tegoprazan-based high-dose dual therapy versus bismuth-containing quadruple therapy for Helicobacter pylori eradication: a prospective, multicentre, randomised controlled trial in Gansu Province, a high-resistance region of China

Background: Potassium-competitive acid blocker-based regimens, such as tegoprazan, have demonstrated promising efficacy for Helicobacter pylori eradication. In regions with high antibiotic resistance, such as Gansu Province, bismuth-containing quadruple therapy (BQT) remains the recommended first-line treatment. However, evidence on the efficacy and safety of high-dose tegoprazan–amoxicillin dual therapy (TA) remains limited. Objectives: To compare the eradication rates and safety profiles of TA and BQT. Design: Prospective, multicentre, randomised controlled trial. Methods: Patients were enrolled from 10 centres across Gansu Province, China, between September and December 2024. Participants were randomised 1:1 to receive either BQT (esomeprazole 20 mg twice daily + bismuth potassium citrate 600 mg twice daily + amoxicillin 1000 mg twice daily + metronidazole 400 mg four times daily) or TA (tegoprazan 50 mg twice daily + amoxicillin 750 mg four times daily) for 14 days. The primary outcome was eradication rate. Secondary outcomes included adverse event (AE) rates, treatment compliance and cost-effectiveness. Results: A total of 288 patients were randomised, with baseline characteristics well balanced between the TA and BQT groups ( p > 0.05). Eradication rates for TA versus BQT were 68.06% (98/144) versus 81.25% (117/144) (difference, −13.19%; 95% confidence interval (CI): −22.95 to −3.43; p = 0.009; non-inferiority p = 0.736) in the intention-to-treat analysis; 69.01% (98/142) versus 81.82% (117/143; difference, −12.81%; 95% CI: −22.70 to −2.90; p = 0.011; non-inferiority p = 0.711) in the modified intention-to-treat analysis; and 72.59% (98/135) versus 89.31% (117/131; difference, −16.72%; 95% CI: −26.01 to −7.43; p < 0.001; non-inferiority p = 0.924) in the per-protocol analysis. AEs were less frequent with TA (8.30% vs 25.70%, p < 0.0001), with similar compliance rates (95.07% vs 91.61%, p = 0.241). Multivariate analysis indicated that long-term residence in the southern region of Gansu Province (including Longnan City and Tianshui) was significantly associated with higher eradication rates compared with the Hexi region (adjusted odds ratio = 5.46, p = 0.04), suggesting that geographical factors independently influenced treatment outcomes. Conclusion: TA did not achieve non-inferiority to BQT and yielded significantly lower eradication rates. The inferior eradication efficacy of TA precludes its recommendation as a first-line therapy in high-resistance settings, such as Gansu. Trial registration: This trial was registered on the Chinese Clinical Trial Registry with the registration number ChiCTR2400081873.