{
  "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.\n\nMethods 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.\n\nEthics 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.\n\nTrial registration number: UMIN000059218.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Anesthesiology and Critical Care Medicine, Division of Acute and Critical Care Medicine, Hokkaido University Faculty of Medicine, Sapporo, Hokkaido, Japan",
    "Department of Emergency Medicine, Osaka Medical and Pharmaceutical University, Takatsuki, Osaka, Japan",
    "Department of Emergency and Disaster Medicine, The Jikei University School of Medicine, Minato, Tokyo, Japan",
    "Department of Emergency and Critical Care Medicine, Keio University School of Medicine, Shinjuku, Tokyo, Japan",
    "Department of Traumatology and Acute Critical Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan",
    "Department of Acute Critical Care and Disaster Medicine, Institute of Science Tokyo Hospital, Bunkyo, Tokyo, Japan",
    "Department of Acute Critical Care Medicine, Tsuchiura Kyodo Hospital, Tsuchiura, Ibaraki, Japan",
    "Department of Intensive Care Medicine, Kameda Medical Center, Kamogawa, Chiba, Japan",
    "Department of Emergency and Critical Care Medicine, Tsukuba Memorial Hospital, Tsukuba, Ibaraki, Japan",
    "Critical Care and Emergency Center, Saitama Medical University International Medical Center, Hidaka, Saitama, Japan",
    "Department of Emergency and Critical Care Medicine, Osaka Medical and Pharmaceutical University, Takatsuki, Osaka, Japan",
    "Department of Emergency and Critical Care, Osaka General Medical Center, Osaka, Osaka, Japan",
    "Emergency and Critical Care Center, Hyogo Prefectural Nishinomiya General Medical Center, Nishinomiya, Hyogo, Japan",
    "Department of Intensive Care Medicine, Sapporo Medical University School of Medicine, Sapporo, Hokkaido, Japan",
    "Department of Emergency Medicine, Shizuoka General Hospital, Shizuoka, Shizuoka, Japan",
    "Department of Emergency and Critical Care Medicine, University of Tsukuba Hospital, Tsukuba, Ibaraki, Japan",
    "Advanced Medical Emergency and Critical Care Center, Yamaguchi University Hospital, Ube, Yamaguchi, Japan",
    "Emergency and Critical Care Medicine, Tokyo Women’s Medical University Adachi Medical Center, Adachi, Tokyo, Japan",
    "Department of Emergency and Critical Care Medicine, Ebina General Hospital, Ebina, Kanagawa, Japan",
    "Department of Acute Medicine, Kawasaki Medical School, Kurashiki, Okayama, Japan",
    "Department of Intensive Care Medicine, Miyazaki Prefectural Miyazaki Hospital, Miyazaki, Miyazaki, Japan",
    "Department of Emergency Medicine, Yokohama City University School of Medicine, Yokohama, Kanagawa, Japan",
    "Osaka Prefectural Nakakawachi Emergency and Critical Care Center, Higashiosaka, Osaka, Japan",
    "Department of Emergency and Critical Care Medicine, Tokai University School of Medicine, Isehara, Kanagawa, Japan",
    "Department of Emergency and Critical Care Medicine, Saga University, Saga, Saga, Japan",
    "Department of Emergency and Critical Care Medicine, Saiseikai Utsunomiya Hospital, Utsunomiya, Tochigi, Japan",
    "Department of Emergency and Critical Care Medicine, Kansai Medical University, Hirakata, Osaka, Japan",
    "M&D Data Science Center, Institute of Science Tokyo, Tokyo, Japan"
  ],
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      "name": "Ryu Azumaguchi"
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      "name": "Chihiro Narita"
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      "name": "Todani Masaki"
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      "name": "Tomohisa Shoko",
      "orcid": "0000-0002-3866-1897"
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      "name": "Takeshi Yamagiwa"
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      "name": "Jiro Takahashi",
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      "name": "Akira Suekane",
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      "name": "Yasufumi Oi",
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      "name": "Hiroshi Matsuura"
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      "name": "Naoya Miura",
      "orcid": "0000-0003-1292-5177"
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      "name": "Hiroyuki Koami"
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      "name": "Kei Kimoto",
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      "name": "Takahiro Oishi"
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      "name": "Kunihiko Takahashi",
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      "name": "Takeshi Wada",
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  "pmcid": "PMC13723868",
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  "published": "2026-10-29",
  "publisher": "BMJ",
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  "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",
  "title_text": "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",
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