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

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.

• Authors: 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
• Journal: Journal of gastroenterology (J Gastroenterol) Vol. 54 Issue 2 Pg. 122-130 (Feb 2019) ISSN: 1435-5922 [Electronic] Japan
• PMID: 29943163 (Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial)

Chemical References

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

Topics

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