Randomized Controlled Trial Comparing the Effects of Vonoprazan Plus Rebamipide and Esomeprazole Plus Rebamipide on Gastric Ulcer Healing Induced by Endoscopic Submucosal Dissection

Abstract

Objective Gastric endoscopic submucosal dissection (ESD) is currently a standard procedure, and proton pump inhibitors (PPIs) are most commonly used to treat post-ESD ulcers. Vonoprazan, a potassium-competitive acid blocker (P-CAB), reportedly inhibits gastric acid secretions more effectively than PPIs. Combination therapy of a PPI plus rebamipide is effective for treating larger ulcers. Our goal was to evaluate the effects of vonoprazan plus rebamipide compared to esomeprazole plus rebamipide for the treatment of post-ESD ulcers. Methods First, vonoprazan plus rebamipide (V group) or esomeprazole plus rebamipide (E group) was orally administered to subjects for eight weeks. We then evaluated the ulcer healing process at four and eight weeks after the procedure using a gastric ulcer stage system and by measuring the ulcer size. Patients A total of 84 patients who underwent ESD for gastric neoplasms between September 2015 and December 2017 in Tsuchiura Kyodo General Hospital were included in this randomized controlled trial. Results The ulcer scar rates at week 4 in the V group (n=43) and E groups (n=39) were 20.9% and 15.4%, while those at week 8 were 90.7% and 92.3%, respectively. The ulcer reduction rates at week 4 in the V and E groups were 94.6% and 93.8%, and those at week 8 were 99.7% and 99.3%, respectively. The ulcer scar rates and reduction rates were not significantly different between the two groups. Conclusion Combination therapy consisting of vonoprazan plus rebamipide was not superior to that of esomeprazole plus rebamipide for post-ESD ulcer healing (UMIN000019516).

Keywords: artificial ulcer; endoscopic submucosal dissection; esomeprazole; gastric intraepithelial neoplasm; ulcer healing; vonoprazan.

Figure 1.

Treatment protocol.

Figure 2.

Endoscopic submucosal dissection (ESD). The pictures of ESD process are shown. The lesion, an early gastric cancer, macroscopic type 0 IIa, 15mm in diameter, is located on the anterior wall in lower third (a). The markings are placed aroud the lesion (b). Hyaluronic acid solution was injected into the submucosal layer, then the mucosal layer is cut around markings (c). The submucosal layer is cut by the endoscopic knife (d). The ESD-induced ulcer was carefully examined, and any visible vessels were coagulated by homeostatic (e). The specimen is attached by pins, and measured the size (f).

Figure 3.

Measurement of ulcer size.

Figure 4.

Flow chart of study design and patient selection outcome.

Figure 5.

Reduction rates of gastric ulcers at 4 weeks and 8 weeks after the ESD. The ulcer reduction rates at week 4 in the V and E groups were 94.6% (95% confidence interval, 91.7-95.8%) and 93.8% (95% confidence interval, 92.1-97.2%) and those at week 8 were 99.7% (95% confidence interval, 99.2-100.2%) and 99.3% (95% confidence interval, 98.2-100.2%), respectively.