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 3rd, Nam K Tran, Leah S Tzimenatos, J Michael Dean, Nathan Kuppermann, TIC-TOC Collaborators of the Pediatric Emergency Care Applied Research Network, Marike Zwienenberg, Joseph Galante, Joseph Stephenson, Alfred F Trappey, Jordan Sandhu, T Charles Casper, Stephen Fenton, Doug Brockmeyer, Theodore Pysher, Michael L Nance, Shih-Shan Lang Chen, Deborah Sesok-Pizzini, Raj Thakkar, Eric Sribnik, Kathleen Nichol, 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 3rd, Nam K Tran, Leah S Tzimenatos, J Michael Dean, Nathan Kuppermann, TIC-TOC Collaborators of the Pediatric Emergency Care Applied Research Network, Marike Zwienenberg, Joseph Galante, Joseph Stephenson, Alfred F Trappey, Jordan Sandhu, T Charles Casper, Stephen Fenton, Doug Brockmeyer, Theodore Pysher, Michael L Nance, Shih-Shan Lang Chen, Deborah Sesok-Pizzini, Raj Thakkar, Eric Sribnik, Kathleen Nichol

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.

Keywords: Children; Tranexamic acid; Trauma.

Conflict of interest statement

Ethics approval and consent to participate

The study was approved by the IRBs at all study sites (central IRB number 00099274 [University of Utah]).

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests at this time.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Study objectives of the TIC-TOC pilot trial
Fig. 2
Fig. 2
Study enrollment procedures. Abbreviations: EFIC exception from informed consent (enrollment without in emergency scenarios when prospective informed consent is not possible); ED emergency department; TXA tranexamic acid
Fig. 3
Fig. 3
Schedule of evaluations. Abbreviations: Cr creatinine, CT computed tomography, GCS Glasgow Coma Scale, GOS-E Peds Pediatric Glasgow Outcome Scale – Extended, Hb hemoglobin, ICP intracranial pressure, INR international normalized ratio, PedsQL Pediatric Quality of Life, TBI traumatic brain injury, TXA tranexamic acid

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