Comparison of rebamipide and tegoprazan combination therapy and tegoprazan monotherapy for ESD induced gastric ulcers a randomized multicenter study

Abstract

Currently, no consensus exists on optimal treatment for post-endoscopic submucosal dissection (ESD) gastric ulcer. This study aims to compare rebamipide and tegoprazan combination therapy with tegoprazan monotherapy for post-ESD ulcer healing. Between May 2022 and September 2023, 140 patients (141 lesions) who underwent ESD for gastric epithelial neoplasms at five tertiary hospitals were randomly assigned to tegoprazan monotherapy or combination therapy groups. The size, stage and healing quality of the post-ESD ulcers were assessed at weeks 4 and 8. Modified intention-to-treat (mITT) and per-protocol analyses included 132 and 121 lesions, respectively. The ulcer healing rate at week 4 was significantly higher in the combination therapy group than in the tegoprazan monotherapy group (96.4% vs. 93.6%, P = 0.02 in mITT). Combination therapy significantly predicted higher-than-average ulcer healing at week 4 (odds ratio 2.28, 95% confidence interval 1.04-5.02, P = 0.04). The proportion of flat ulcer scar at week 8 was significantly higher in the combination group than in the tegoprazan monotherapy group (73.8% vs. 48.4%, P = 0.007). Combination treatment with rebamipide and tegoprazan led to faster ulcer healing and the development of high-quality post-ESD scars compared to tegoprazan monotherapy.

Keywords: Endoscopic submucosal dissection; Gastric ulcer; Rebamipide; Tegoprazan.

Fig. 1

Flow chart of the study. ESD, endoscopic submucosal dissection; ITT, intention to treat; PP, per-protocol.

Fig. 2

Representative images for quality of post-ESD ulcer scar at 8 weeks after ESD: flat scar (a), intermediate scar (b), and nodular scar (c). Flat scars were defined as lesions with smooth mucosal healing without any elevation; nodular scars exhibited one or more elevated nodular components at the ulcer base or margin; intermediate scars were characterized by ambiguous features that did not fully meet the criteria for either flat or nodular types. ESD, endoscopic submucosal dissection.