Efficacy of vonoprazan in prevention of bleeding from endoscopic submucosal dissection-induced gastric ulcers: a prospective randomized phase II study

Background: Vonoprazan, potassium-competitive acid blocker, is expected to reduce incidence of delayed bleeding after gastric endoscopic submucosal dissection (ESD); however, preliminary data to design a large-scale comparative study are lacking. This study aimed to assess the efficacy of vonoprazan in preventing delayed bleeding after gastric ESD. Methods: In this single-center randomized phase II trial, a modified screened selection design was used with a threshold non-bleeding rate of 89% and an expected rate of 97%. In this design, Simon’s optimal two-stage design was first applied for each parallel group, and efficacy was evaluated in comparison with the threshold rate using binomial testing. Patients were randomly assigned in a 1:1 ratio to receive either vonoprazan 20 mg (VPZ group) or lansoprazole 30 mg (PPI group) for 8 weeks from the day before gastric ESD. The primary endpoint was the incidence of delayed bleeding, defined as endoscopically confirmed bleeding accompanied by hematemesis, melena, or a decrease in hemoglobin of ≥ 2 g/dl. Results: Delayed bleeding occurred in three of 69 patients (4.3%, 95% CI 0.9–12.2%, p = 0.047) in the VPZ group, and four of 70 (5.7%, 95% CI 1.6–14.0%, p = 0.104) in the PPI group. As only vonoprazan showed significant reduction in delayed bleeding compared with the threshold rate, it was determined to be efficacious treatment. Conclusions: Vonoprazan efficaciously reduced the delayed bleeding rate in patients with an ESD-induced gastric ulcer. A large-scale, randomized, phase III study is warranted to definitively test the effectiveness of vonoprazan compared with proton pump inhibitors.