{
  "abstract": "Introduction Venous thromboembolism (VTE) is a common complication of traumatic brain injury (TBI) and is associated with increased morbidity and mortality. Low molecular weight heparin (LMWH) is recommended for prophylaxis against VTE after trauma but may increase the risk of progression of intracranial bleeding. Limited evidence exists to guide clinicians regarding the optimal timing of VTE prophylaxis in patients with acute TBI. This randomised controlled trial (RCT) will directly compare the safety and effectiveness of early versus delayed initiation of LMWH in patients with moderate to severe TBI.Methods and analysis The study design is a Bayesian adaptive RCT comparing early (within three calendar days of injury) versus delayed (after study Day 7) VTE prophylaxis with the LMWH, dalteparin. All patients receive sequential compression devices until study Day 8. The co-primary effectiveness outcome is the development of clinically important VTE at study Day 8. The co-primary safety outcome is the development of clinically important intracranial bleeding at study Day 8. Secondary outcomes are mortality and functional outcomes (Glasgow Outcome Scale Extended and EQ-5D) measured at study Days 30 and 180; clinically diagnosed VTE to Day 30 and progression of intracranial bleeding to Day 8.Ethics and dissemination This study has been approved through Clinical Trials Ontario’s streamlined ethics review process (board of record, Sunnybrook Health Sciences Centre) and all participating centres. It is conducted in accordance with the Declaration of Helsinki, Good Clinical Practice guidelines and Health Canada regulatory requirements. We anticipate that the trial will achieve wide dissemination through publication in a peer-reviewed medical journal and presentation at international conferences targeting the fields of critical care, trauma and neurosurgery. The results of this trial will help guide clinicians aiming to balance the risks and benefits of early anticoagulant prophylaxis after TBI and will inform guideline development.Trial registration number NCT03559114.",
  "authors": [
    {
      "affiliations": [
        "Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, Ontario, Canada",
        "Division of Neurosurgery, Department of Surgery, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada"
      ],
      "name": "Farhad Pirouzmand"
    },
    {
      "affiliations": [
        "Interdepartmental Division of Critical Care, University of Toronto, Toronto, Ontario, Canada",
        "Division of Neurosurgery, Department of Surgery, Unity Health Toronto, Toronto, Ontario, Canada"
      ],
      "name": "Francois Mathieu"
    },
    {
      "affiliations": [
        "Neurosurgery, Penn State Cancer Institute, Hershey, Pennsylvania, USA"
      ],
      "name": "Alireza Mansouri"
    },
    {
      "affiliations": [
        "The Centre for Clinical Trial Support, Sunnybrook Research Institute, Toronto, Ontario, Canada"
      ],
      "name": "Kanthi Kavikondala"
    },
    {
      "affiliations": [
        "Division of Neurosurgery, Department of Surgery, Queen’s University, Kingston, Ontario, Canada",
        "Neurosurgery, Kingston Health Sciences Centre, Kingston, Ontario, Canada"
      ],
      "name": "Ryan Alkins"
    },
    {
      "affiliations": [
        "Department of Critical Care Medicine, Queen’s University, Kingston, Ontario, Canada"
      ],
      "name": "J Gordon Boyd"
    },
    {
      "affiliations": [
        "Neurosurgery, Dalhousie University, Halifax, Nova Scotia, Canada"
      ],
      "name": "Sean Christie"
    },
    {
      "affiliations": [
        "Department of Critical Care Medicine, University of Calgary, Calgary, Alberta, Canada",
        "UCalgary Cumming School of Medicine, Calgary, Alberta, Canada"
      ],
      "name": "Philippe Couillard"
    },
    {
      "affiliations": [
        "Division of Neurosurgery, Department of Surgery, Unity Health Toronto, Toronto, Ontario, Canada"
      ],
      "name": "Michael D Cusimano"
    },
    {
      "affiliations": [
        "Surgery, McMaster University, Hamilton, Ontario, Canada",
        "Department of Critical Care, Hamilton Health Sciences, Hamilton, Ontario, Canada"
      ],
      "name": "Paul T Engels"
    },
    {
      "affiliations": [
        "Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada",
        "Division of Critical Care, Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada",
        "School of Epidemiology and Public Health, University of Ottawa, Ottawa, Ontario, Canada"
      ],
      "name": "Shane English"
    },
    {
      "affiliations": [
        "Division of Neurosurgery, Department of Surgery, University of Saskatchewan, Saskatoon, Saskatchewan, Canada"
      ],
      "name": "Daryl Fourney"
    },
    {
      "affiliations": [
        "Interdepartmental Division of Critical Care, University of Toronto, Toronto, Ontario, Canada",
        "Critical Care Medicine, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada"
      ],
      "name": "Robert Fowler"
    },
    {
      "affiliations": [
        "Department of Medicine, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada",
        "Medicine, University of Toronto, Toronto, Ontario, Canada"
      ],
      "name": "William Geerts"
    },
    {
      "affiliations": [
        "Division of Neurosurgery, Department of Surgery, Vancouver General Hospital, Vancouver, British Columbia, Canada",
        "Division of Neurosurgery, Department of Surgery, The University of British Columbia - Vancouver Campus, Vancouver, British Columbia, Canada"
      ],
      "name": "Peter A Gooderham"
    },
    {
      "affiliations": [
        "Centre for Clinical Epidemiology & Evaluation, Vancouver Coastal Health Research Institute Clinical Research Unit, Vancouver, British Columbia, Canada",
        "Department of Anesthesiology, Pharmacology & Therapeutics, The University of British Columbia - Vancouver Campus, Vancouver, British Columbia, Canada"
      ],
      "name": "Donald Griesdale"
    },
    {
      "affiliations": [
        "Neurology, University of Saskatchewan, Saskatoon, Saskatchewan, Canada"
      ],
      "name": "Gary Hunter"
    },
    {
      "affiliations": [
        "Department of Medical Imaging, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada"
      ],
      "name": "Pejman Jabehdar Maralani"
    },
    {
      "affiliations": [
        "Division of Neurosurgery, Department of Surgery, University of Saskatchewan, Saskatoon, Saskatchewan, Canada"
      ],
      "name": "Michael E Kelly"
    },
    {
      "affiliations": [
        "Centre for Clinical Trial Support, Sunnybrook Research Institute, Toronto, Ontario, Canada"
      ],
      "name": "Gail Klein"
    },
    {
      "affiliations": [
        "Departments of Critical Care Medicine, University of Calgary Cumming School of Medicine, Calgary, Alberta, Canada",
        "Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada"
      ],
      "name": "Andreas H Kramer"
    },
    {
      "affiliations": [
        "Departments of Critical Care Medicine, University of Calgary Cumming School of Medicine, Calgary, Alberta, Canada",
        "Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada"
      ],
      "name": "Julie Kromm"
    },
    {
      "affiliations": [
        "Critical Care Medicine, University of Alberta Faculty of Medicine and Dentistry, Edmonton, Alberta, Canada"
      ],
      "name": "Demetrios J Kutsogiannis"
    },
    {
      "affiliations": [
        "Population Health and Optimal Health Practices Research Unit (Trauma-Emergency-Critical Care Medicine), Centre Hospitalier Universitaire de Québec-Université Laval, Québec City, Quebec, Canada",
        "Department of Medicine and Department of Anesthesiology & Critical Care, Université Laval, Québec City, Quebec, Canada"
      ],
      "name": "Francois Lauzier"
    },
    {
      "affiliations": [
        "Department of Medical Imaging, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada"
      ],
      "name": "Matylda Machnowska"
    },
    {
      "affiliations": [
        "Department of Critical Care Medicine, Queen’s University, Kingston, Ontario, Canada",
        "Critical Care Medicine, Kingston Health Sciences Centre, Kingston, Ontario, Canada"
      ],
      "name": "David M Maslove"
    },
    {
      "affiliations": [
        "Fundación Valle del Lili, Cali, Colombia"
      ],
      "name": "Jorge Mejia-Mantilla"
    },
    {
      "affiliations": [
        "Department of Clinical Neurosciences, University of Calgary Cumming School of Medicine, Calgary, Alberta, Canada"
      ],
      "name": "Rajiv Midha"
    },
    {
      "affiliations": [
        "Department of Surgery, P D Hinduja National Hospital and Medical Research Centre, Mumbai, Maharashtra, India"
      ],
      "name": "Basant Misra"
    },
    {
      "affiliations": [
        "Critical Care, Dalhousie University, Halifax, Nova Scotia, Canada"
      ],
      "name": "Laurel Murphy"
    },
    {
      "affiliations": [
        "Division of Neurosurgery, Department of Surgery, University of Alberta, Edmonton, Alberta, Canada"
      ],
      "name": "C J O’Kelly"
    },
    {
      "affiliations": [
        "Department of Medical Imaging, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada",
        "Medical Imaging, University of Toronto, Toronto, Ontario, Canada"
      ],
      "name": "Chirag Patel"
    },
    {
      "affiliations": [
        "Interdepartmental Division of Critical Care, University of Toronto, Toronto, Ontario, Canada",
        "Critical Care Medicine, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada"
      ],
      "name": "Ruxandra L Pinto"
    },
    {
      "affiliations": [
        "Interdepartmental Division of Critical Care, University of Toronto, Toronto, Ontario, Canada",
        "Critical Care Medicine, Unity Health Toronto, Toronto, Ontario, Canada"
      ],
      "name": "Antoine P Pronovost"
    },
    {
      "affiliations": [
        "Critical Care, The University of British Columbia - Vancouver Campus, Vancouver, British Columbia, Canada"
      ],
      "name": "Mypinder Sekhon"
    },
    {
      "affiliations": [
        "Surgery, McMaster University, Hamilton, Ontario, Canada",
        "Neurosurgery, Hamilton Health Sciences, Hamilton, Ontario, Canada"
      ],
      "name": "Sunjay V Sharma"
    },
    {
      "affiliations": [
        "Division of Neurosurgery, Department of Surgery, Ottawa Hospital, Ottawa, Ontario, Canada",
        "Division of Neurosurgery, University of Ottawa, Ottawa, Ontario, Canada"
      ],
      "name": "John Sinclair"
    },
    {
      "affiliations": [
        "Division of Neurosurgery, University of Ottawa, Ottawa, Ontario, Canada",
        "Neurosurgery, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada"
      ],
      "name": "Eve Tsai"
    },
    {
      "affiliations": [
        "Population Health and Optimal Health Practices Research Unit (Trauma-Emergency-Critical Care Medicine), Centre Hospitalier Universitaire de Québec-Université Laval, Québec City, Quebec, Canada",
        "Anesthesia and Critical Care Medicine, Université Laval Faculté de Médecine, Québec City, Quebec, Canada"
      ],
      "name": "Alexis F Turgeon"
    },
    {
      "affiliations": [
        "Department of Surgery, P D Hinduja National Hospital and Medical Research Centre, Mumbai, Maharashtra, India"
      ],
      "name": "Abhijit Warade"
    },
    {
      "affiliations": [
        "Interdepartmental Division of Critical Care, University of Toronto, Toronto, Ontario, Canada",
        "Critical Care Medicine, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada"
      ],
      "name": "Damon C Scales"
    },
    {
      "affiliations": [],
      "name": "PROTEST investigators"
    }
  ],
  "title": "Prophylaxis for venous thromboembolism in traumatic brain injury: protocol for a randomised controlled trial",
  "uid": "a378f5f9-56bf-5b9e-bc2e-aebbaad3cb09"
}