Prophylaxis for venous thromboembolism in traumatic brain injury: protocol for a randomised controlled trial.
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.
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.
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.
NCT03559114.
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.
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.
NCT03559114.
Authors
Pirouzmand Pirouzmand, Mathieu Mathieu, Mansouri Mansouri, Kavikondala Kavikondala, Alkins Alkins, Boyd Boyd, Christie Christie, Couillard Couillard, Cusimano Cusimano, Engels Engels, English English, Fourney Fourney, Fowler Fowler, Geerts Geerts, Gooderham Gooderham, Griesdale Griesdale, Hunter Hunter, Jabehdar Maralani Jabehdar Maralani, Kelly Kelly, Klein Klein, Kramer Kramer, Kromm Kromm, Kutsogiannis Kutsogiannis, Lauzier Lauzier, Machnowska Machnowska, Maslove Maslove, Mejia-Mantilla Mejia-Mantilla, Midha Midha, Misra Misra, Murphy Murphy, O'Kelly O'Kelly, Patel Patel, Pinto Pinto, Pronovost Pronovost, Sekhon Sekhon, Sharma Sharma, Sinclair Sinclair, Tsai Tsai, Turgeon Turgeon, Warade Warade, Scales Scales,
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