{
  "abstract": "Introduction Traumatic brain injury (TBI) often causes permanent neurological dysfunction. Although no medication has been validated yet to prevent secondary injury of brain tissue, recent animal studies have reported that perampanel, a glutamine receptor antagonist, could improve the neurological functions of animals with TBI by mitigating the abnormal calcium influx and cell death around the site of primary injury. The present study aims to elucidate the efficacy of perampanel administration in improving the neurological function of patients with TBI.Methods and analysis The perampanel for alleviation of secondary injury in TBI trial is a multicentre, phase-II, open-label randomised controlled trial targeting patients with mild-to-moderate TBI. This trial will include adult TBI patients with a Glasgow Coma Scale score of 9–14 from five tertiary centres. Patients with epilepsy as a comorbidity, delayed presentation of symptoms (>24 hours after injury) or Injury Severity Score of ≥25 will be excluded. The study participants will be randomly assigned to either the perampanel group (2 mg/day) or the control group (fosphenytoin administered at a dose of 15–18 mg/kg/day, followed by 5–7.5 mg/kg/day of fosphenytoin). In both groups, the medication will be initiated within 12 hours of the TBI diagnosis and continued for 7 days. The antiepileptic drugs can be increased, changed or added as necessary if early post-traumatic seizures are observed. The primary outcome is favourable neurological outcome, defined as a Glasgow Outcome Scale Extended score of ≥5 at 90 days after the TBI diagnosis, which will then be compared between the groups through an intention-to-treat analysis.Ethics and dissemination The present study has been approved by the Certified Review Board of Keio at the principal institution (approval number: N20240004). Written informed consent will be obtained from all participants or their legal representatives. The results will be disseminated via publications and presentations.Trial registration number Japan Registry of Clinical Trials (jRCTs031250067).",
  "authors": [
    {
      "affiliations": [
        "Department of Emergency and Critical Care Medicine, Keio University School of Medicine, Tokyo, Japan"
      ],
      "name": "Ryo Yamamoto"
    },
    {
      "affiliations": [
        "Department of Neurosurgery, Keio University School of Medicine, Tokyo, Japan"
      ],
      "name": "Ryota Tamura"
    },
    {
      "affiliations": [
        "Department of Neurosurgery, Tokyo Saiseikai Central Hospital, Tokyo, Japan"
      ],
      "name": "Yukina Morimoto"
    },
    {
      "affiliations": [
        "Department of Neurosurgery, Tokyo Saiseikai Central Hospital, Tokyo, Japan"
      ],
      "name": "Masato Nakaya"
    },
    {
      "affiliations": [
        "Department of Neurosurgery, Tokyo Saiseikai Central Hospital, Tokyo, Japan"
      ],
      "name": "Satoshi Terao"
    },
    {
      "affiliations": [
        "Department of Emergency and Critical Care Medicine, Tokyo Saiseikai Central Hospital, Tokyo, Japan"
      ],
      "name": "Takahiro Shoji"
    },
    {
      "affiliations": [
        "Department of Neurosurgery, Saiseikai Yokohamashi Tobu Hospital, Kanagawa, Japan"
      ],
      "name": "Tokunori Kanazawa"
    },
    {
      "affiliations": [
        "Department of Neurosurgery, Saiseikai Yokohamashi Tobu Hospital, Kanagawa, Japan"
      ],
      "name": "Ryota Sasao"
    },
    {
      "affiliations": [
        "Department of Neurosurgery, Saiseikai Yokohamashi Tobu Hospital, Kanagawa, Japan"
      ],
      "name": "Makoto Inaba"
    },
    {
      "affiliations": [
        "Department of Trauma and Emergency Surgery, Saiseikai Yokohamashi Tobu Hospital, Kanagawa, Japan"
      ],
      "name": "Masayuki Shimizu"
    },
    {
      "affiliations": [
        "Department of Neurosurgery, Kawasaki Municipal Hospital, Kanagawa, Japan"
      ],
      "name": "Yuki Kuranari"
    },
    {
      "affiliations": [
        "Department of Neurosurgery, Kawasaki Municipal Hospital, Kanagawa, Japan"
      ],
      "name": "Makoto Katayama"
    },
    {
      "affiliations": [
        "Emergency Department, Kawasaki Municipal Hospital, Kanagawa, Japan"
      ],
      "name": "Koichi Ueno"
    },
    {
      "affiliations": [
        "Department of Neurosurgery, Hiratsuka City Hospital, Kanagawa, Japan"
      ],
      "name": "Yumiko Oishi"
    },
    {
      "affiliations": [
        "Department of Neurosurgery, Hiratsuka City Hospital, Kanagawa, Japan"
      ],
      "name": "Akiyoshi Nakamura"
    },
    {
      "affiliations": [
        "Department of Emergency and Critical Care Medicine, Hiratsuka City Hospital, Kanagawa, Japan"
      ],
      "name": "Yo Kikuo"
    },
    {
      "affiliations": [
        "Department of Emergency and Critical Care Medicine, Keio University School of Medicine, Tokyo, Japan"
      ],
      "name": "Ryosuke Murakami"
    },
    {
      "affiliations": [
        "Department of Emergency and Critical Care Medicine, Keio University School of Medicine, Tokyo, Japan"
      ],
      "name": "Koichiro Homma"
    },
    {
      "affiliations": [
        "Department of Neurosurgery, Keio University School of Medicine, Tokyo, Japan"
      ],
      "name": "Sota Wakahara"
    },
    {
      "affiliations": [
        "Department of Neurosurgery, Keio University School of Medicine, Tokyo, Japan"
      ],
      "name": "Konosuke Ishikawa"
    },
    {
      "affiliations": [
        "Department of Neurosurgery, Keio University School of Medicine, Tokyo, Japan"
      ],
      "name": "Kenzo Kosugi"
    },
    {
      "affiliations": [
        "Department of Neurosurgery, Keio University School of Medicine, Tokyo, Japan"
      ],
      "name": "Masahiro Toda"
    },
    {
      "affiliations": [
        "Biostatistics Unit, Clinical and Translational Research Center, Keio University Hospital, Tokyo, Japan"
      ],
      "name": "Tatsuro Ozaki"
    },
    {
      "affiliations": [
        "Department of Emergency and Critical Care Medicine, Keio University School of Medicine, Tokyo, Japan"
      ],
      "name": "Junichi Sasaki"
    }
  ],
  "title": "Perampanel for alleviation of secondary injury in traumatic brain injury (PEACE-TBI): a protocol for a phase-II multicentre randomised clinical trial",
  "uid": "489fbed0-94eb-5a39-b35e-9e97d0bf6b4f"
}