{
  "abstract": "Introduction Chronic subdural haematoma (CSDH) is a common neurosurgical condition in older adults, with a recurrence rate of approximately 7.1–13% after burr-hole drainage. Although surgical adjuncts such as subdural drains and middle meningeal artery embolisation may reduce recurrence, these are not suitable for all patients. Pharmacological strategies, including tranexamic acid, Goreisan and carbazochrome sodium sulfonate hydrate, have shown potential, but high-level evidence remains lacking. A prior retrospective study suggested that a triple oral regimen combining these agents may reduce recurrence. This randomised controlled trial aims to evaluate its efficacy and safety.Methods and analysis This is a prospective, multicentre, open-label, randomised controlled trial conducted across six hospitals in Ibaraki, Japan. A total of 180 patients undergoing first-time burr-hole surgery for CSDH will be randomised 1:1 to receive either triple therapy (Goreisan 7.5 g/day, carbazochrome sodium sulfonate hydrate 90 mg/day and tranexamic acid 750 mg/day for up to 90 days) or standard postoperative care. The primary outcome is recurrence requiring reoperation within 90 days. Secondary outcomes include time to recurrence and haematoma volume reduction on serial CT imaging. All analyses will follow the intention-to-treat principle, using logistic regression, Cox proportional hazards models and mixed-effects models.Ethics and dissemination Written, informed consent will be obtained from all participants at each participating hospital by trained staff from that hospital. The trial protocol has been approved by the ethics committee of the University of Tsukuba Hospital (approval no. TCRB23-025) and the Institutional Review Boards of all participating centres. Study findings will be disseminated through presentations at scientific conferences and publications in peer-reviewed journals. A summary of the results will also be provided to participating institutions and made publicly available in accordance with the BMJ Open data sharing policy.Trial registration number jRCTs031240007.",
  "authors": [
    {
      "affiliations": [
        "Department of Neurosurgery, Mito Medical Center, Higashiibaraki, Japan"
      ],
      "name": "Haruka Negishi"
    },
    {
      "affiliations": [
        "Department of Neurosurgery, Institute of Medicine, University of Tsukuba, Tsukuba, Japan",
        "Department of Stroke and Cerebrovascular Diseases, University of Tsukuba Hospital, Tsukuba, Japan"
      ],
      "name": "Koji Hirata"
    },
    {
      "affiliations": [
        "Department of Neurosurgery, Tsukuba Memorial Hospital, Tsukuba, Japan"
      ],
      "name": "Hitoshi Aiyama"
    },
    {
      "affiliations": [
        "Department of Neurosurgery, Ibaraki Seinan Medical Center Hospital, Sashima, Japan"
      ],
      "name": "Keishi Fujita"
    },
    {
      "affiliations": [
        "Department of Neurosurgery, Hitachi General Hospital, Hitachi, Japan"
      ],
      "name": "Yoji Komatsu"
    },
    {
      "affiliations": [
        "Department of Neurosurgery, Mito Medical Center, Higashiibaraki, Japan"
      ],
      "name": "Noriyuki Kato"
    },
    {
      "affiliations": [
        "Department of Neurosurgery, Mito Kyodo General Hospital, Mito, Japan"
      ],
      "name": "Yasushi Shibata"
    },
    {
      "affiliations": [
        "Department of Neurosurgery, Ibaraki Seinan Medical Center Hospital, Sashima, Japan"
      ],
      "name": "Kyoji Tsuda"
    },
    {
      "affiliations": [
        "Department of Neurosurgery, Hitachi General Hospital, Hitachi, Japan"
      ],
      "name": "Tomosato Yamazaki"
    },
    {
      "affiliations": [
        "Department of Neurosurgery, Mito Medical Center, Higashiibaraki, Japan"
      ],
      "name": "Masayuki Sato"
    },
    {
      "affiliations": [
        "Department of Neurosurgery, Mito Kyodo General Hospital, Mito, Japan"
      ],
      "name": "Shinya Watanabe"
    },
    {
      "affiliations": [
        "Department of Neurosurgery, Institute of Medicine, University of Tsukuba, Tsukuba, Japan"
      ],
      "name": "Narushi Sugii"
    },
    {
      "affiliations": [
        "Department of Radiology, Tsukuba Medical Center Hospital, Tsukuba, Japan"
      ],
      "name": "Takahiro Konishi"
    },
    {
      "affiliations": [
        "Department of Cardiovascular Surgery, Institute of Medicine, University of Tsukuba, Tsukuba, Japan"
      ],
      "name": "Bryan J Mathis"
    },
    {
      "affiliations": [
        "Department of Biostatistics, Tsukuba Clinical Research & Development Organization (T-CReDO), University of Tsukuba, Tsukuba, Japan"
      ],
      "name": "Tomohiro Ohigashi"
    },
    {
      "affiliations": [
        "Tsukuba Clinical Research and Development Organization (T-CReDO), University of Tsukuba, Tsukuba, Japan"
      ],
      "name": "Mitsuhiko Endo"
    },
    {
      "affiliations": [
        "Department of Neurosurgery, Institute of Medicine, University of Tsukuba, Tsukuba, Japan"
      ],
      "name": "Eiichi Ishikawa"
    },
    {
      "affiliations": [
        "Department of Neurosurgery, Institute of Medicine, University of Tsukuba, Tsukuba, Japan"
      ],
      "name": "Yuji Matsumaru"
    },
    {
      "affiliations": [],
      "name": "The Triple Study Investigators"
    }
  ],
  "title": "Triple-drug therapy with Goreisan, tranexamic acid and carbazochrome sodium sulfonate hydrate to prevent recurrence after chronic subdural haematoma surgery: a multicentre, randomised, controlled trial protocol",
  "uid": "6bd4df57-8c27-5517-987a-54a2bc0f6962"
}