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Peer-reviewedCC BY-NC 4.0BMJ Open

Effects of perfusion-guided permissive hypotension and early vasopressin initiation in adults with septic shock: protocol for a multicentre 2×2 factorial randomised controlled trial in Japanese intensive care units

  • Akira Endo1
  • Kazuma Yamakawa2
  • Takashi Tagami3
  • Ryo Yamamoto4
  • Yutaka Umemura5
  • Wataru Takayama6
  • Hiromasa Hoshi7
  • Yoshiro Hayashi8
  • Akira Komori9
  • Takuto Yanagisawa10
  • Ryo Hisamune11
  • Yudai Yoshino3
18 more authors
  • Shuhei Murao12
  • Satoshi Okubo13
  • Ryu Azumaguchi14
  • Chihiro Narita15
  • Takahiro Ono16
  • Todani Masaki17
  • Tomohisa Shoko18
  • Takeshi Yamagiwa19
  • Jiro Takahashi20
  • Akira Suekane21
  • Yasufumi Oi22
  • Hiroshi Matsuura23
  • Naoya Miura24
  • Hiroyuki Koami25
  • Kei Kimoto26
  • Takahiro Oishi27
  • Kunihiko Takahashi28
  • Takeshi Wada1
28 affiliations
  1. 1Department of Anesthesiology and Critical Care Medicine, Division of Acute and Critical Care Medicine, Hokkaido University Faculty of Medicine, Sapporo, Hokkaido, Japan
  2. 2Department of Emergency Medicine, Osaka Medical and Pharmaceutical University, Takatsuki, Osaka, Japan
  3. 3Department of Emergency and Disaster Medicine, The Jikei University School of Medicine, Minato, Tokyo, Japan
  4. 4Department of Emergency and Critical Care Medicine, Keio University School of Medicine, Shinjuku, Tokyo, Japan
  5. 5Department of Traumatology and Acute Critical Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
  6. 6Department of Acute Critical Care and Disaster Medicine, Institute of Science Tokyo Hospital, Bunkyo, Tokyo, Japan
  7. 7Department of Acute Critical Care Medicine, Tsuchiura Kyodo Hospital, Tsuchiura, Ibaraki, Japan
  8. 8Department of Intensive Care Medicine, Kameda Medical Center, Kamogawa, Chiba, Japan
  9. 9Department of Emergency and Critical Care Medicine, Tsukuba Memorial Hospital, Tsukuba, Ibaraki, Japan
  10. 10Critical Care and Emergency Center, Saitama Medical University International Medical Center, Hidaka, Saitama, Japan
  11. 11Department of Emergency and Critical Care Medicine, Osaka Medical and Pharmaceutical University, Takatsuki, Osaka, Japan
  12. 12Department of Emergency and Critical Care, Osaka General Medical Center, Osaka, Osaka, Japan
  13. 13Emergency and Critical Care Center, Hyogo Prefectural Nishinomiya General Medical Center, Nishinomiya, Hyogo, Japan
  14. 14Department of Intensive Care Medicine, Sapporo Medical University School of Medicine, Sapporo, Hokkaido, Japan
  15. 15Department of Emergency Medicine, Shizuoka General Hospital, Shizuoka, Shizuoka, Japan
  16. 16Department of Emergency and Critical Care Medicine, University of Tsukuba Hospital, Tsukuba, Ibaraki, Japan
  17. 17Advanced Medical Emergency and Critical Care Center, Yamaguchi University Hospital, Ube, Yamaguchi, Japan
  18. 18Emergency and Critical Care Medicine, Tokyo Women’s Medical University Adachi Medical Center, Adachi, Tokyo, Japan
  19. 19Department of Emergency and Critical Care Medicine, Ebina General Hospital, Ebina, Kanagawa, Japan
  20. 20Department of Acute Medicine, Kawasaki Medical School, Kurashiki, Okayama, Japan
  21. 21Department of Intensive Care Medicine, Miyazaki Prefectural Miyazaki Hospital, Miyazaki, Miyazaki, Japan
  22. 22Department of Emergency Medicine, Yokohama City University School of Medicine, Yokohama, Kanagawa, Japan
  23. 23Osaka Prefectural Nakakawachi Emergency and Critical Care Center, Higashiosaka, Osaka, Japan
  24. 24Department of Emergency and Critical Care Medicine, Tokai University School of Medicine, Isehara, Kanagawa, Japan
  25. 25Department of Emergency and Critical Care Medicine, Saga University, Saga, Saga, Japan
  26. 26Department of Emergency and Critical Care Medicine, Saiseikai Utsunomiya Hospital, Utsunomiya, Tochigi, Japan
  27. 27Department of Emergency and Critical Care Medicine, Kansai Medical University, Hirakata, Osaka, Japan
  28. 28M&D Data Science Center, Institute of Science Tokyo, Tokyo, Japan
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Abstract

Introduction: The optimal blood pressure target during early resuscitation in septic shock remains uncertain. Recent randomised controlled trials suggest that strategies targeting lower mean arterial pressure (MAP) than the guideline-recommended threshold of 65 mm Hg may be beneficial. Individualised resuscitation strategies guided by peripheral perfusion indicators, such as capillary refill time (CRT), have also shown potential effectiveness. Meanwhile, vasopressin, which has recently been proposed for early concomitant initiation, may influence CRT through its strong vasoconstrictive effects, potentially affecting peripheral perfusion-guided management.

Methods and analysis: A multicentre, pragmatic, open-label randomised controlled trial with a 2×2 factorial design will be conducted to evaluate the effectiveness of a peripheral perfusion-guided individualised permissive hypotension strategy, considering its interaction with the timing of vasopressin initiation. Adult patients with septic shock will be randomly assigned to permissive hypotension versus usual MAP care and to early versus standard vasopressin initiation. In the permissive hypotension group, the target MAP will be decreased in 5 mm Hg increments as long as CRT remains <3 s, whereas usual MAP care will target MAP ≥65 mm Hg. Vasopressin will be initiated when the norepinephrine dose exceeds 0.1 µg/kg/min in the early group and 0.3 µg/kg/min in the standard vasopressin group. The primary outcome is vasopressor-free days within 28 days.

Ethics and dissemination: The trial will be performed in accordance with the principles of the Declaration of Helsinki and Ethical Guidelines for Medical and Health Research Involving Human Subjects in Japan. The Medical Research Ethics Committee of the Institute of Science Tokyo, the ethics committee of the principal institution, approved this trial. Written informed consent will be obtained from all patients or their representatives. The findings of this trial will be presented at relevant scientific conferences and disseminated through publication in a peer-reviewed journal.

Trial registration number: UMIN000059218.

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Cite

BibTeXRIS
BibTeX
@article{endo2026effects,
  title = {{Effects of perfusion-guided permissive hypotension and early vasopressin initiation in adults with septic shock: protocol for a multicentre 2×2 factorial randomised controlled trial in Japanese intensive care units}},
  author = {Akira Endo and Kazuma Yamakawa and Takashi Tagami and Ryo Yamamoto and Yutaka Umemura and Wataru Takayama and Hiromasa Hoshi and Yoshiro Hayashi and Akira Komori and Takuto Yanagisawa and Ryo Hisamune and Yudai Yoshino and Shuhei Murao and Satoshi Okubo and Ryu Azumaguchi and Chihiro Narita and Takahiro Ono and Todani Masaki and Tomohisa Shoko and Takeshi Yamagiwa and Jiro Takahashi and Akira Suekane and Yasufumi Oi and Hiroshi Matsuura and Naoya Miura and Hiroyuki Koami and Kei Kimoto and Takahiro Oishi and Kunihiko Takahashi and Takeshi Wada},
  journal = {BMJ Open},
  year = {2026},
  month = oct,
  doi = {10.1136/bmjopen-2026-126112},
  url = {https://bmjopen.bmj.com/lookup/doi/10.1136/bmjopen-2026-126112},
  note = {CC BY-NC 4.0},
}
RIS
TY  - JOUR
TI  - Effects of perfusion-guided permissive hypotension and early vasopressin initiation in adults with septic shock: protocol for a multicentre 2×2 factorial randomised controlled trial in Japanese intensive care units
AU  - Akira Endo
AU  - Kazuma Yamakawa
AU  - Takashi Tagami
AU  - Ryo Yamamoto
AU  - Yutaka Umemura
AU  - Wataru Takayama
AU  - Hiromasa Hoshi
AU  - Yoshiro Hayashi
AU  - Akira Komori
AU  - Takuto Yanagisawa
AU  - Ryo Hisamune
AU  - Yudai Yoshino
AU  - Shuhei Murao
AU  - Satoshi Okubo
AU  - Ryu Azumaguchi
AU  - Chihiro Narita
AU  - Takahiro Ono
AU  - Todani Masaki
AU  - Tomohisa Shoko
AU  - Takeshi Yamagiwa
AU  - Jiro Takahashi
AU  - Akira Suekane
AU  - Yasufumi Oi
AU  - Hiroshi Matsuura
AU  - Naoya Miura
AU  - Hiroyuki Koami
AU  - Kei Kimoto
AU  - Takahiro Oishi
AU  - Kunihiko Takahashi
AU  - Takeshi Wada
PY  - 2026
DA  - 2026/10/29
JO  - BMJ Open
DO  - 10.1136/bmjopen-2026-126112
UR  - https://bmjopen.bmj.com/lookup/doi/10.1136/bmjopen-2026-126112
AB  - Introduction: The optimal blood pressure target during early resuscitation in septic shock remains uncertain. Recent randomised controlled trials suggest that strategies targeting lower mean arterial pressure (MAP) than the guideline-recommended threshold of 65 mm Hg may be beneficial. Individualised resuscitation strategies guided by peripheral perfusion indicators, such as capillary refill time (CRT), have also shown potential effectiveness. Meanwhile, vasopressin, which has recently been proposed for early concomitant initiation, may influence CRT through its strong vasoconstrictive effects, potentially affecting peripheral perfusion-guided management.  Methods and analysis: A multicentre, pragmatic, open-label randomised controlled trial with a 2×2 factorial design will be conducted to evaluate the effectiveness of a peripheral perfusion-guided individualised permissive hypotension strategy, considering its interaction with the timing of vasopressin initiation. Adult patients with septic shock will be randomly assigned to permissive hypotension versus usual MAP care and to early versus standard vasopressin initiation. In the permissive hypotension group, the target MAP will be decreased in 5 mm Hg increments as long as CRT remains <3 s, whereas usual MAP care will target MAP ≥65 mm Hg. Vasopressin will be initiated when the norepinephrine dose exceeds 0.1 µg/kg/min in the early group and 0.3 µg/kg/min in the standard vasopressin group. The primary outcome is vasopressor-free days within 28 days.  Ethics and dissemination: The trial will be performed in accordance with the principles of the Declaration of Helsinki and Ethical Guidelines for Medical and Health Research Involving Human Subjects in Japan. The Medical Research Ethics Committee of the Institute of Science Tokyo, the ethics committee of the principal institution, approved this trial. Written informed consent will be obtained from all patients or their representatives. The findings of this trial will be presented at relevant scientific conferences and disseminated through publication in a peer-reviewed journal.  Trial registration number: UMIN000059218.
SN  - 2044-6055
SN  - 2044-6055
ER  -