Traumatic injury clinical trial evaluating tranexamic acid in children (TIC-TOC): study protocol for a pilot randomized controlled trial
Daniel K. Nishijima,
John VanBuren,
Hilary A. Hewes,
Sage R. Myers,
Rachel M. Stanley,
P. David Adelson,
Sarah E. Barnhard,
Matthew Bobinski,
Simona Ghetti,
James F. Holmes,
Ian Roberts,
Walton O. Schalick,
Nam K. Tran,
Leah S. Tzimenatos,
J. Michael Dean,
Nathan Kuppermann,
for the TIC-TOC Collaborators of the Pediatric Emergency Care Applied Research Network
Affiliations
Daniel K. Nishijima
Department of Emergency Medicine, UC Davis School of Medicine
John VanBuren
Department of Pediatrics, University of Utah School of Medicine
Hilary A. Hewes
Department of Pediatrics, Division of Pediatric Emergency Medicine, University of Utah School of Medicine, Primary Children’s Hospital
Sage R. Myers
Department of Pediatrics, Division of Pediatric Emergency Medicine, Perelman School of Medicine at the University of Pennsylvania, Children’s Hospital of Philadelphia
Rachel M. Stanley
Department of Pediatrics, Division of Pediatric Emergency Medicine, Ohio State University School of Medicine, Nationwide Children’s Hospital
P. David Adelson
Department of Pediatric Neurosciences, Barrow Neurological Institute at Phoenix Children’s Hospital
Sarah E. Barnhard
Department of Pathology and Laboratory Medicine, UC Davis School of Medicine
Matthew Bobinski
Department of Radiology, UC Davis School of Medicine
Simona Ghetti
Department of Psychology, University of California, Davis
James F. Holmes
Department of Emergency Medicine, UC Davis School of Medicine
Ian Roberts
Department of Population Health, London School of Hygiene and Tropical Medicine
Walton O. Schalick
Department of Orthopedics and Rehabilitation, University of Wisconsin
Nam K. Tran
Department of Pathology and Laboratory Medicine, University of California, Davis
Leah S. Tzimenatos
Department of Emergency Medicine, UC Davis School of Medicine
J. Michael Dean
Department of Pediatrics, University of Utah School of Medicine
Nathan Kuppermann
Departments of Emergency Medicine and Pediatrics, UC Davis School of Medicine
for the TIC-TOC Collaborators of the Pediatric Emergency Care Applied Research Network
Abstract Background Trauma is the leading cause of morbidity and mortality in children in the United States. The antifibrinolytic drug tranexamic acid (TXA) improves survival in adults with traumatic hemorrhage, however, the drug has not been evaluated in a clinical trial in severely injured children. We designed the Traumatic Injury Clinical Trial Evaluating Tranexamic Acid in Children (TIC-TOC) trial to evaluate the feasibility of conducting a confirmatory clinical trial that evaluates the effects of TXA in children with severe trauma and hemorrhagic injuries. Methods Children with severe trauma and evidence of hemorrhagic torso or brain injuries will be randomized to one of three arms: (1) TXA dose A (15 mg/kg bolus dose over 20 min, followed by 2 mg/kg/hr infusion over 8 h), (2) TXA dose B (30 mg/kg bolus dose over 20 min, followed by 4 mg/kg/hr infusion over 8 h), or (3) placebo. We will use permuted-block randomization by injury type: hemorrhagic brain injury, hemorrhagic torso injury, and combined hemorrhagic brain and torso injury. The trial will be conducted at four pediatric Level I trauma centers. We will collect the following outcome measures: global functioning as measured by the Pediatric Quality of Life (PedsQL) and Pediatric Glasgow Outcome Scale Extended (GOS-E Peds), working memory (digit span test), total amount of blood products transfused in the initial 48 h, intracranial hemorrhage progression at 24 h, coagulation biomarkers, and adverse events (specifically thromboembolic events and seizures). Discussion This multicenter trial will provide important preliminary data and assess the feasibility of conducting a confirmatory clinical trial that evaluates the benefits of TXA in children with severe trauma and hemorrhagic injuries to the torso and/or brain. Trial registration ClinicalTrials.gov registration number: NCT02840097. Registered on 14 July 2016.
