Tegoprazan-Based Triple Therapy for Helicobacter pylori Eradication: A Phase III Multicenter Randomized Clinical Trial

Abstract

Background: Tegoprazan, a potassium-competitive acid blocker, offers potent and sustained acid inhibition and potentially improves eradication efficacy.

Aim: This study aimed to evaluate the efficacy and safety of tegoprazan-based triple therapy with two dosing regimens compared with that of lansoprazole-based therapy for first-line Helicobacter pylori eradication.

Methods: This randomized, double-blind, active-controlled, multicenter trial was conducted at 19 referral hospitals in South Korea (February 2023-April 2024). Treatment-naïve adults with H. pylori infection were randomized 1:1:1 to receive 14-day triple therapy with tegoprazan, 50 mg (TAC1), tegoprazan, 100 mg (TAC2), or lansoprazole, 30 mg (LAC), each combined with amoxicillin 1000 mg and clarithromycin 500 mg, administered twice daily. The primary endpoint was H. pylori eradication rate in the modified intention-to-treat (mITT) population, with a non-inferiority margin of -10%. Secondary endpoints included subgroup analyses based on clarithromycin resistance and safety assessments.

Results: Of the 564 screened patients, 382 were randomized. In the mITT analysis (mean age, 54.9 years; 54.3% male), eradication rates were 86.0%, 85.5%, and 78.7% for TAC1, TAC2, and LAC, respectively. Both tegoprazan-based regimens met the non-inferiority criteria. Among clarithromycin-resistant infections, the eradication rates were higher for TAC1 (47.8%) and TAC2 (50.0%) than for LAC (35.5%), although the difference was not statistically significant. Safety profiles were comparable across the groups, with no serious drug-related adverse events.

Conclusion: Tegoprazan-based triple therapies, at 50- and 100-mg doses, were non-inferior to lansoprazole-based therapy and were well tolerated. Our findings indicated that tegoprazan-based triple therapy is a viable first-line option for H. pylori eradication.

Trial registration: ClinicalTrials.gov identifier: NCT05933031.

Keywords: Helicobacter pylori; eradication; potassium‐competitive acid blocker; randomized clinical trials; tegoprazan.

FIGURE 1

Overview of study protocol.

FIGURE 2

Study enrolment, randomization, and treatment allocation. LAC: lansoprazole 30 mg‐based triple therapy; TAC1: tegoprazan 50 mg‐based triple therapy; TAC2: tegoprazan 100 mg‐based triple therapy. All regimens included amoxicillin 1000 mg and clarithromycin 500 mg, administered orally twice daily before meals for 14 days. The modified intention‐to‐treat (mITT) population comprised all randomized participants who met the eligibility criteria and received at least one dose of the study drug. Participants with < 80% treatment compliance (assessed at Visit 3 within Day 15 + 3) were excluded from the per‐protocol set (PPS), along with those with major protocol deviations (e.g., early withdrawal, prohibited medication use). Missing data for Helicobacter pylori eradication were handled as treatment failure in the mITT analyses.