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

J Gastroenterol. 2019 Feb;54(2):122-130. doi: 10.1007/s00535-018-1487-6. Epub 2018 Jun 25.

Abstract

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.

Keywords: Endoscopic submucosal dissection; Gastric cancer; P-CAB; Potassium-competitive acid blocker; Vonoprazan.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Endoscopic Mucosal Resection / adverse effects
  • Female
  • Hematemesis / blood
  • Hematemesis / etiology
  • Hematemesis / prevention & control
  • Hemoglobins / metabolism
  • Humans
  • Lansoprazole / therapeutic use
  • Male
  • Melena / blood
  • Melena / etiology
  • Melena / prevention & control
  • Middle Aged
  • Postoperative Hemorrhage / blood
  • Postoperative Hemorrhage / etiology
  • Postoperative Hemorrhage / prevention & control*
  • Prospective Studies
  • Proton Pump Inhibitors / therapeutic use*
  • Pyrroles / therapeutic use*
  • Stomach Neoplasms / surgery*
  • Stomach Ulcer / complications
  • Stomach Ulcer / drug therapy*
  • Sulfonamides / therapeutic use*

Substances

  • 1-(5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl)-N-methylmethanamine
  • Hemoglobins
  • Proton Pump Inhibitors
  • Pyrroles
  • Sulfonamides
  • Lansoprazole