Tegoprazan-based versus esomeprazole-based triple therapy plus bismuth for first-line Helicobacter pylori eradication: A nationwide, multicenter, double-blind, double-dummy, randomized controlled trial.

Background: Although triple therapy plus bismuth (TTPB), comprising a proton pump inhibitor (PPI), two antibiotics, and bismuth, is widely used to eradicate Helicobacter pylori (H. pylori), eradication rates have been suboptimal. Potassium-competitive acid blockers (P-CABs) offer stronger and more stable gastric acid inhibition compared to PPIs. This study aimed to compare the efficacy, safety, and compliance of tegoprazan-based TTPB (TACB) vs. esomeprazole-based TTPB (EACB) in treatment-naïve patients with H. pylori infection.

Methods: In this nationwide, multicenter, double-blind, double-dummy, randomized controlled trial conducted from October 2022 to September 2023 across 41 centers in China, 561 eligible patients with H. pylori infection were randomized (1:1) to receive either TACB (tegoprazan 50 mg, amoxicillin 1000 mg, clarithromycin 500 mg, and bismuth 220 mg) or EACB (esomeprazole 20 mg, amoxicillin 1000 mg, clarithromycin 500 mg, and bismuth 220 mg), all administered twice daily for 14 days. H. pylori eradication was assessed using the 13C-urea breath test at 4-8 weeks post-treatment. The primary endpoint was eradication rate based on the full analysis set (FAS). Statistical analysis included the chi-squared tests, with a predefined non-inferiority margin of -10%.

Results: In the FAS population, eradication rates were 93.5% (95% confidence interval [CI]: 89.9-96.1%) in the TACB group and 86.4% (95% CI: 81.9-90.2%) in the EACB group. The between-group difference was 7.0% (95% CI: 2.1-12.0%), indicating that tegoprazan-based TTPB was non-inferior to esomeprazole-based TTPB. Furthermore, superiority tests found a significantly higher eradication rate in tegoprazan group compared with esomeprazole group (P = 0.006). Similar results were observed in the per-protocol set. The incidence of treatment-emergent adverse events was comparable between groups (75.5% in TACB vs. 73.4% in EACB), with most events being mild and transient. Compliance was high in both groups (98.4% vs. 98.8%).

Conclusion: TACB was non-inferior to EACB in H. pylori eradication efficacy, with similar safety and compliance profiles in Chinese treatment-naïve patients.

Trial Registration: ClinicalTrials.gov identifier: NCT05577468.