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Treatment with vonoprazan for 3 weeks is not inferior to 8 weeks for the management of gastric ESD: a multicenter noninferiority randomized study

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Abstract

Background

Vonoprazan, a potassium-competitive acid blocker (VPZ), significantly reduces postoperative bleeding after gastric ESD; however, there is no consensus on the appropriate treatment duration. We conducted a randomized controlled study to demonstrate that the 3-week administration of VPZ is not inferior to the 8-week administration for ulcer healing.

Methods

This is a prospective, open-label multicenter randomized controlled trial. Patients aged 20–85 years undergoing gastric ESD were included in this study. The key exclusion criteria were patients with bleeding tendencies and those taking NSAIDs, steroids, PPIs, or VPZ medications. Eligible patients were randomly assigned to the VPZ 3w or 8w treatment group. The primary endpoint was the proportion of patients with complete closure of the post-ESD wound at 24 weeks after ESD. The key secondary endpoints included the proportion of patients with complete closure of the post-ESD wound at 8 weeks and the proportion of bleeding or perforation more than 3 weeks after ESD.

Results

From May 2018 to October 2020, 234 patients were included. The proportion of patients with complete ulcer closure was significantly lower in the 3w group than in the 8w group (70.8% vs. 90.6%) at 8 weeks post-treatment. The complete closure rates at 24 weeks in the 3w and 8w groups were 99.1% and 99.2%, respectively. The absolute difference in the closure rate at 24 weeks was − 0.059% [95% confidence interval (CI) -3.4% to 3.2], and the lower limit of the 95% CI exceeded -10%, the preset threshold. None of the patients developed delayed bleeding 3 weeks after ESD.

Conclusion

This multicenter randomized study demonstrated that 3 weeks of treatment with VPZ is sufficient for ulcer healing.

Trial registry number. UMIN000031564.

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Abbreviations

ESD:

Endoscopic submucosal dissection

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Acknowledgements

We thank Dr. Masaru Nakano (Kitasato University Kitasato Institute Hospital), Dr. Yusaku Tanaka, Dr. Akira Okazawa (Keiyu Hospital), Dr. Atsushi Nakazawa (Saiseikai Central Hospital), and Dr. Ai Fujimoto (Toho University School of Medicine) for reviewing and evaluating the study concept, data collection, analysis, and interpretation.

Author information

Authors and Affiliations

  1. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan

    Motohiko Kato, Yoko Kubosawa & Takanori Kanai

  2. Division of Research and Development for Minimally Invasive Treatment, Cancer Center, Keio University School of Medicine, Tokyo, Japan

    Motohiko Kato, Yoko Kubosawa & Naohisa Yahagi

  3. Center for Diagnostic and Therapeutic Endoscopy, Keio University School of Medicine, Tokyo, Japan

    Naoki Hosoe

  4. Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan

    Takuji Gotoda

  5. Department of Gastroenterology, Kitasato University School of Medicine, Kanagawa, Japan

    Chika Kusano & Toshiki Horii

  6. Department of Gastroenterology and Hepatology, National Hospital Organization Saitama Hospital, Saitama, Japan

    Mizuki Kuramochi

  7. Department of Gastroenterology and Hepatology, Eiju General Hospital, Tokyo, Japan

    Hideo Yoshida

  8. Division of Gastrointestinal Endoscopy, NTT Medical Center Tokyo, Tokyo, Japan

    Yoshiaki Kimoto

  9. Department of Gastroenterology and Hepatology, Sano Kosei General Hospital, Tochigi, Japan

    Yukishige Okamura

  10. Department of Gastroenterology, Saitama Medical University Hospital, Saitama, Japan

    Hiroyuki Imaeda

  11. Department of Gastroenterology, Keiyu Hospital, Yokohama, Japan

    Takafumi Ito

  12. Department of Gastroenterology, Kitasato University Kitasato Institute Hospital, Tokyo, Japan

    Yasuo Miyamoto

  13. Department of Gastroenterology, Yuri Kumiai General Hospital, Akita, Japan

    Toshiki Horii

  14. Department of Gastroenterology and Hepatology, National Hospital Organization Tokyo Medical Center, Tokyo, Japan

    Hideki Mori

  15. Translational Research Center for Gastrointestinal Disorders (TARGID), University of Leuven, Louvain, Belgium

    Hideki Mori

  16. Department of Gastroenterology and Hepatology, Yokohama Municipal Citizen’s Hospital, Yokohama, Japan

    Yuichi Morohoshi

  17. Department of Gastroenterology and Hepatology, Kyorin University School of Medicine, Tokyo, Japan

    Akiko Ohno

  18. Department of Internal Medicine, Saiseikai Central Hospital, Tokyo, Japan

    Ryohei Kishino

  19. Center for Integrated Medical Research, Hiroshima University, Hiroshima, Japan

    Kenichi Yoshimura

Authors
  1. Motohiko Kato
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  2. Naoki Hosoe
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  3. Takuji Gotoda
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  4. Chika Kusano
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  5. Mizuki Kuramochi
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  6. Hideo Yoshida
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  7. Yoshiaki Kimoto
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  8. Yukishige Okamura
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  9. Hiroyuki Imaeda
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  10. Takafumi Ito
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  11. Yasuo Miyamoto
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  12. Toshiki Horii
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  13. Hideki Mori
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  14. Yuichi Morohoshi
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  15. Akiko Ohno
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  16. Ryohei Kishino
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  17. Yoko Kubosawa
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  18. Kenichi Yoshimura
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  19. Naohisa Yahagi
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  20. Takanori Kanai
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Contributions

Motohiko Kato determined the initial study concept and design; Motohiko Kato, Naoki Hosoe, Takuji Gotoda, Mizuki Kuramochi, Hideo Yoshida, Yoshiaki Kimoto, Yukishige Okamura, Hiroyuki Imaeda, Takafumi Ito, Yasuo Miyamoto, Toshiki Horii, Hideki Mori, Yuichi Morohoshi, Akiko Ohno, Ryohei Kishino, Yoko Kubosawa, Chika Kusano, Yoko Kubosawa acquired the data; Motohiko Kato analyzed and interpreted the data; Motohiko Kato drafted the manuscript; Naoki Hosoe, Takuji Gotoda, Mizuki Kuramochi, Hideo Yoshida, Yoshiaki Kimoto, Yukishige Okamura, Hiroyuki Imaeda, Takafumi Ito, Yasuo Miyamoto, Toshiki Horii, Hideki Mori, Yuichi Morohoshi, Akiko Ohno, Ryohei Kishino, Yoko Kubosawa, Chika Kusano, Kenichi Yoshimura, Naohisa Yahagi, and Takanori Kanai critically revised the manuscript for important intellectual content; and Motohiko Kato and Kenichi Yoshimura performed the statistical analysis.

Corresponding author

Correspondence to Motohiko Kato.

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Kato, M., Hosoe, N., Gotoda, T. et al. Treatment with vonoprazan for 3 weeks is not inferior to 8 weeks for the management of gastric ESD: a multicenter noninferiority randomized study. J Gastroenterol 58, 358–366 (2023). https://doi.org/10.1007/s00535-023-01966-z

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  • DOI: https://doi.org/10.1007/s00535-023-01966-z

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