Randomized Controlled Trial
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 14, 2018; 24(14): 1550-1561
Published online Apr 14, 2018. doi: 10.3748/wjg.v24.i14.1550
Maintenance for healed erosive esophagitis: Phase III comparison of vonoprazan with lansoprazole
Kiyoshi Ashida, Katsuhiko Iwakiri, Naoki Hiramatsu, Yuuichi Sakurai, Tetsuharu Hori, Kentarou Kudou, Akira Nishimura, Eiji Umegaki
Kiyoshi Ashida, Department of Gastroenterology, Rakuwakai Otowa Hospital, Kyoto 607-8062, Japan
Katsuhiko Iwakiri, Department of Gastroenterology, Nippon Medical School Graduate School of Medicine, Tokyo 113-8603, Japan
Naoki Hiramatsu, Department of Gastroenterology and Hepatology, Osaka Rosai Hospital, Sakai, Osaka 591-8025, Japan
Yuuichi Sakurai, Tetsuharu Hori, Kentarou Kudou, Akira Nishimura, Takeda Pharmaceutical Company Limited, Osaka 540-8645, Japan
Eiji Umegaki, Department of Gastroenterology, Kobe University Graduate School of Medicine, Kobe, Hyogo 650-0017, Japan
Author contributions: Ashida K, Sakurai Y, Hori T and Nishimura A were involved in study conception and design; Hiramatsu N served as Medical Expert; Umegaki E, Iwakiri K and Ashida K served as the Central Adjudication Committee; Kudou K conducted statistical analyses; all authors were involved in the drafting and critical revision of the manuscript, and approved the final version, including the authorship list.
Institutional review board statement: The study was reviewed and approved by the institutional review board of each participating site.
Clinical trial registration statement: This study is registered at ClinicalTrials.gov. The registration identification number is NCT01459367.
Informed consent statement: All study participants provided written informed consent prior to study enrollment.
Conflict-of-interest statement: Kiyoshi Ashida has received fees and honoraria from Takeda Pharmaceutical Company Limited and Otsuka Pharmaceutical Company Limited; Katsuhiko Iwakiri has received grants, fees, and honoraria from Takeda Pharmaceutical Company Limited, and fees from Otsuka Pharmaceutical Company Limited; Yuuichi Sakurai, Tetsuharu Hori, Kentarou Kudou, and Akira Nishimura are full-time employees of Takeda Pharmaceutical Company Limited; Naoki Hiramatsu and Eiji Umegaki have no conflicts of interest to declare.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Kiyoshi Ashida, MD, PhD, Department of Gastroenterology, Rakuwakai Otowa Hospital, 2 Otowachinji-cho, Yamashina-ku, Kyoto 607-8062, Japan. rakuwadr1185@rakuwadr.com
Telephone: +81-75-5934111 Fax: +81-75-5934160
Received: November 30, 2017
Peer-review started: December 1, 2017
First decision: December 13, 2017
Revised: February 6, 2018
Accepted: March 7, 2018
Article in press: March 6, 2018
Published online: April 14, 2018

To compare vonoprazan 10 and 20 mg vs lansoprazole 15 mg as maintenance therapy in healed erosive esophagitis (EE).


A total of 607 patients aged ≥ 20 years, with endoscopically-confirmed healed EE following 8 wk of treatment with vonoprazan 20 mg once daily, were randomized 1:1:1 to receive lansoprazole 15 mg (n = 201), vonoprazan 10 mg (n = 202), or vonoprazan 20 mg (n = 204), once daily. The primary endpoint of the study was the rate of endoscopically-confirmed EE recurrence during a 24-wk maintenance period. The secondary endpoint was the EE recurrence rate at Week 12 during maintenance treatment. Additional efficacy endpoints included the incidence of heartburn and acid reflux, and the EE healing rate 4 wk after the initiation of maintenance treatment. Safety endpoints comprised adverse events (AEs), vital signs, electrocardiogram findings, clinical laboratory results, serum gastrin and pepsinogen I/II levels, and gastric mucosa histopathology results.


Rates of EE recurrence during the 24-wk maintenance period were 16.8%, 5.1%, and 2.0% with lansoprazole 15 mg, vonoprazan 10 mg, and vonoprazan 20 mg, respectively. Vonoprazan was shown to be non-inferior to lansoprazole 15 mg (P < 0.0001 for both doses). In a post-hoc analysis, EE recurrence at Week 24 was significantly reduced with vonoprazan at both the 10 mg and the 20 mg dose vs lansoprazole 15 mg (5.1% vs 16.8%, P = 0.0002, and 2.0% vs 16.8%, P < 0.0001, respectively); by contrast, the EE recurrence rate did not differ significantly between the two doses of vonoprazan (P = 0.1090). The safety profiles of vonoprazan 10 and 20 mg were similar to that of lansoprazole 15 mg in patients with healed EE. Treatment-related AEs were reported in 11.4%, 10.4%, and 10.3% of patients in the lansoprazole 15 mg, vonoprazan 10 mg, and vonoprazan 20 mg arms, respectively.


Our findings confirm the non-inferiority of vonoprazan 10 and 20 mg to lansoprazole 15 mg as maintenance therapy for patients with healed EE.

Keywords: Gastroesophageal reflux disease, Erosive esophagitis, Lansoprazole, Potassium-competitive acid blockers, Vonoprazan, Maintenance therapy

Core tip: Proton pump inhibitors (PPIs), including lansoprazole, are widely used to maintain healing of erosive esophagitis (EE) in patients with gastroesophageal reflux disease; however, symptoms of reflux persist in significant numbers of patients treated with PPIs. We compared two doses of the novel potassium-competitive acid blocker vonoprazan (10 and 20 mg once daily) with lansoprazole at its approved dose of 15 mg once daily as maintenance therapy for healed EE in 607 Japanese patients. Vonoprazan was shown to be non-inferior to lansoprazole 15 mg at both investigated doses, while demonstrating a similar safety profile.