S3160 A Randomized, Double-Blind, Active-Controlled, Multicenter Study to Evaluate the Safety and Efficacy of Tegoprazan-Based Standard Triple Therapy for Helicobacter pylori Eradication

Introduction: Potassium-competitive acid blockers (P-CABs) offer prolonged acid suppression and are promising agents for Helicobacter pylori eradication. We aimed to assess the efficacy and safety of tegoprazan-based standard triple therapy (STT). Methods: This multicenter, randomized, active-controlled study enrolled treatment-naïve adults with H. pylori infection in 18 institutions from February 2023 to April 2024. Participants were randomized 1:1:1 to receive tegoprazan 50 mg (TAC1), tegoprazan 100 mg (TAC2), or lansoprazole 30 mg (LAC) with amoxicillin 1000 mg and clarithromycin 500 mg twice daily for 14 days. The primary endpoint was the eradication rate, analyzed in the modified intention-to-treat (mITT) population and per-protocol set (PPS). Non-inferiority was established if the lower bound of the 95% confidence interval (CI) for the difference in eradication rates was greater than -10%. Secondary endpoints included subgroup analyses stratified by clarithromycin resistance and safety assessments. Results: Of the 382 randomized patients, 364 completed the study. In the mITT popluation, eradication rates were 85.95% for TAC1, 85.48% for TAC2, and 78.74% for LAC. Both TAC1 (P = 0.0002 vs LAC) and TAC2 (P = 0.0003 vs LAC) demonstrated non-inferiority. In the PPS, eradication rates were 88.50% for TAC1, 87.39% for TAC2, and 81.30% for LAC, with TAC1 (P < 0.0001 vs LAC) and TAC2 (P = 0.0003 vs LAC) maintaining non-inferiority. Among clarithromycin-resistant strains, eradication rates were numerically higher in TAC1 and TAC2 (47.8% and 50.0%) vs LAC (35.6%) in the mITT analysis, without statistical significance. No significant differences in adverse event rates were observed across groups, and no serious adverse events occurred. Conclusion: Tegoprazan-based STT demonstrated non-inferiority to lansoprazole-based STT, achieving eradication rates above 80% in the mITT analysis. Given its efficacy and safety profile, tegoprazan-based triple therapy may serve as an effective first-line treatment option for H. pylori eradication.