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Article History

Received: 3 October 2025

Accepted: 30 October 2025

First Online: 18 November 2025

Declarations

:

: Koichiro Kuwahara received research grants or contracts from Kowa Co., Ltd.; AstraZeneca; Daiichi Sankyo Co., Ltd.; Novo Nordisk Pharma Ltd.; Amgen; Janssen Pharmaceutical; Parexel International Inc.; Astellas Pharma Inc.; Otsuka Pharmaceutical Co., Ltd.; Mitsubishi Tanabe Pharma Corp.; Nippon Boehringer Ingelheim Co., Ltd.; Kyowa Kirin Co., Ltd.; Medtronic Japan Co. Ltd.; Boston Scientific Japan; Abbott Japan LLC; Japan Lifeline Co., Ltd.; Biotronik Japan; Terumo Corporation; Nipro Corporation; and Cordis Japan and has consulted for Astellas Pharma Inc.; AstraZeneca; MSD; Otsuka Pharmaceutical Co., Ltd.; Ono Pharmaceutical Co., Ltd.; Kyowa Kirin Co., Ltd.; Kowa Co., Ltd.; Sanofi, Sumitomo Dainippon Pharma Co., Ltd. (Sumitomo Pharma Co., Ltd.); Mitsubishi Tanabe Pharma Corp., Eli Lilly Japan; Nippon Boehringer Ingelheim Co., Ltd.; Novartis Pharma; Novo Nordisk Pharma Ltd.; Bayer Yakuhin, Ltd.; Pfizer Japan Inc.; and Janssen Pharmaceutical. The other authors, Kazuhiro Kimura, Yoshiko Takagi, Makoto Harada, Shinichiro Ueda, Masatoshi Minamisawa, Kosuke Sonoda, Ako Oiwa, Yoshikazu Yazaki, Shunpei Sakurai, Takeshi Tomita, Kazuaki Kaneko, Kazuya Yamamoto, Noriaki Takama, Shigeki Momose, Yoshito Inobe, Kazutaka Nogi, Megumi Koshikawa, Takuo Misawa, Toshio Kasai, Hiroshi Tsutsui, Noboru Watanabe, Kyohei Yamazaki, Takahide Miyamoto, Takashi Midorikawa, Tatsuya Usui, Tatsuya Saigusa, Hirohiko Motoki, Yoshihiko Saito, Yuji Kamijo, Mitsuhisa Komatsu, have nothing to disclose.

: The principal investigator and members of the protocol committee designed and conducted this study in accordance with the Clinical Trials Act and Ethical Guidelines for Medical and Biological Research Involving Human Subjects in Japan. The protocol, consent forms, important protocol modifications, and safety information including causally related serious adverse events (SAEs) in this trial were reviewed and approved by Shinshu University Certified Review Board of Clinical Research (CRB3180014) and Niigata University Central Review Board of Clinical Research (CRB3180025), and permitted by the institutional head at each participating center (Table  ). These approvals covered all participating institutions, and each site obtained permission from its institutional head based on the central review board approval. All patients or their legally authorized representatives provided written informed consent before randomization. All centers were regularly monitored by protocol committee representatives, and the trial was monitored by an independent data and safety monitoring board. An independent auditor audited each trial. This trial has been registered at ClinicalTrials.gov (NCT05469659). This study was conducted in accordance with the principles of the Declaration of Helsinki. All enrolled patients provided written informed consent before participation.