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

  • Kenta Hamada
  • Noriya Uedo
  • Yusuke Tonai
  • Masamichi Arao
  • Sho Suzuki
  • Taro Iwatsubo
  • Minoru Kato
  • Satoki Shichijo
  • Yasushi Yamasaki
  • Noriko Matsuura
  • Hiroko Nakahira
  • Takashi Kanesaka
  • Sachiko Yamamoto
  • Tomofumi Akasaka
  • Noboru Hanaoka
  • Yoji Takeuchi
  • Koji Higashino
  • Ryu Ishihara
  • Hiroyuki Okada
  • Hiroyasu Iishi
  • Keisuke Fukui
  • Toshio Shimokawa
Original Article—Alimentary Tract
  • 393 Downloads

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

Vonoprazan Potassium-competitive acid blocker P-CAB Endoscopic submucosal dissection Gastric cancer 

Notes

Funding

None.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

Osaka International Cancer Institute Ethics Committee.

Supplementary material

535_2018_1487_MOESM1_ESM.doc (32 kb)
Supplementary material 1 (DOC 32 kb)

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Copyright information

© Japanese Society of Gastroenterology 2018

Authors and Affiliations

  • Kenta Hamada
    • 1
    • 2
  • Noriya Uedo
    • 1
  • Yusuke Tonai
    • 1
  • Masamichi Arao
    • 1
  • Sho Suzuki
    • 1
  • Taro Iwatsubo
    • 1
  • Minoru Kato
    • 1
  • Satoki Shichijo
    • 1
  • Yasushi Yamasaki
    • 1
    • 2
  • Noriko Matsuura
    • 1
  • Hiroko Nakahira
    • 1
  • Takashi Kanesaka
    • 1
  • Sachiko Yamamoto
    • 1
  • Tomofumi Akasaka
    • 1
  • Noboru Hanaoka
    • 1
  • Yoji Takeuchi
    • 1
  • Koji Higashino
    • 1
  • Ryu Ishihara
    • 1
  • Hiroyuki Okada
    • 2
  • Hiroyasu Iishi
    • 1
  • Keisuke Fukui
    • 3
  • Toshio Shimokawa
    • 4
  1. 1.Department of Gastrointestinal OncologyOsaka International Cancer InstituteOsakaJapan
  2. 2.Department of Gastroenterology and HepatologyOkayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesOkayamaJapan
  3. 3.Department of Cancer Control and StatisticsOsaka International Cancer InstituteOsakaJapan
  4. 4.Clinical Study Support CenterWakayama Medical UniversityWakayamaJapan

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