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 & 2 others Keisuke Fukui, Toshio Shimokawa

Research output: Contribution to journalArticle

4 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1-9
Number of pages9
JournalJournal of Gastroenterology
DOIs
Publication statusAccepted/In press - Jun 25 2018

Fingerprint

Stomach Ulcer
Hemorrhage
Stomach
Lansoprazole
Melena
Hematemesis
Proton Pump Inhibitors
Incidence
1-(5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl)-N-methylmethanamine
Endoscopic Mucosal Resection
Potassium
Hemoglobins
Acids

Keywords

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

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Efficacy of vonoprazan in prevention of bleeding from endoscopic submucosal dissection-induced gastric ulcers : a prospective randomized phase II study. / Hamada, Kenta; Uedo, Noriya; Tonai, Yusuke; Arao, Masamichi; Suzuki, Sho; Iwatsubo, Taro; Kato, Minoru; Shichijo, Satoki; Yamasaki, Yasushi; Matsuura, Noriko; Nakahira, Hiroko; Kanesaka, Takashi; Yamamoto, Sachiko; Akasaka, Tomofumi; Hanaoka, Noboru; Takeuchi, Yoji; Higashino, Koji; Ishihara, Ryu; Okada, Hiroyuki; Iishi, Hiroyasu; Fukui, Keisuke; Shimokawa, Toshio.

In: Journal of Gastroenterology, 25.06.2018, p. 1-9.

Research output: Contribution to journalArticle

Hamada, K, Uedo, N, Tonai, Y, Arao, M, Suzuki, S, Iwatsubo, T, Kato, M, Shichijo, S, Yamasaki, Y, Matsuura, N, Nakahira, H, Kanesaka, T, Yamamoto, S, Akasaka, T, Hanaoka, N, Takeuchi, Y, Higashino, K, Ishihara, R, Okada, H, Iishi, H, Fukui, K & Shimokawa, T 2018, 'Efficacy of vonoprazan in prevention of bleeding from endoscopic submucosal dissection-induced gastric ulcers: a prospective randomized phase II study', Journal of Gastroenterology, pp. 1-9. https://doi.org/10.1007/s00535-018-1487-6
Hamada, Kenta ; Uedo, Noriya ; Tonai, Yusuke ; Arao, Masamichi ; Suzuki, Sho ; Iwatsubo, Taro ; Kato, Minoru ; Shichijo, Satoki ; Yamasaki, Yasushi ; Matsuura, Noriko ; Nakahira, Hiroko ; Kanesaka, Takashi ; Yamamoto, Sachiko ; Akasaka, Tomofumi ; Hanaoka, Noboru ; Takeuchi, Yoji ; Higashino, Koji ; Ishihara, Ryu ; Okada, Hiroyuki ; Iishi, Hiroyasu ; Fukui, Keisuke ; Shimokawa, Toshio. / Efficacy of vonoprazan in prevention of bleeding from endoscopic submucosal dissection-induced gastric ulcers : a prospective randomized phase II study. In: Journal of Gastroenterology. 2018 ; pp. 1-9.
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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.",
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T1 - Efficacy of vonoprazan in prevention of bleeding from endoscopic submucosal dissection-induced gastric ulcers

T2 - a prospective randomized phase II study

AU - Hamada, Kenta

AU - Uedo, Noriya

AU - Tonai, Yusuke

AU - Arao, Masamichi

AU - Suzuki, Sho

AU - Iwatsubo, Taro

AU - Kato, Minoru

AU - Shichijo, Satoki

AU - Yamasaki, Yasushi

AU - Matsuura, Noriko

AU - Nakahira, Hiroko

AU - Kanesaka, Takashi

AU - Yamamoto, Sachiko

AU - Akasaka, Tomofumi

AU - Hanaoka, Noboru

AU - Takeuchi, Yoji

AU - Higashino, Koji

AU - Ishihara, Ryu

AU - Okada, Hiroyuki

AU - Iishi, Hiroyasu

AU - Fukui, Keisuke

AU - Shimokawa, Toshio

PY - 2018/6/25

Y1 - 2018/6/25

N2 - 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.

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KW - Endoscopic submucosal dissection

KW - Gastric cancer

KW - P-CAB

KW - Potassium-competitive acid blocker

KW - Vonoprazan

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