Traumatic injury clinical trial evaluating tranexamic acid in children (TIC-TOC): a pilot randomized trial

Daniel K Nishijima; John M VanBuren; Seth W Linakis; Hilary A Hewes; Sage R Myers; Matthew Bobinski; Nam K Tran; Simona Ghetti; P David Adelson; Ian Roberts; James F Holmes; Walton O Schalick 3rd; J Michael Dean; T Charles Casper; Nathan Kuppermann; TIC-TOC Collaborators of the Pediatric Emergency Care Applied Research Network (PECARN)

doi:10.1111/acem.14481

Traumatic injury clinical trial evaluating tranexamic acid in children (TIC-TOC): a pilot randomized trial

Acad Emerg Med. 2022 Mar 10:10.1111/acem.14481. doi: 10.1111/acem.14481. Online ahead of print.

Authors

Daniel K Nishijima¹, John M VanBuren², Seth W Linakis³, Hilary A Hewes⁴, Sage R Myers⁵, Matthew Bobinski⁶, Nam K Tran⁷, Simona Ghetti⁸, P David Adelson⁹, Ian Roberts¹⁰, James F Holmes¹, Walton O Schalick 3rd¹¹, J Michael Dean², T Charles Casper², Nathan Kuppermann¹²; TIC-TOC Collaborators of the Pediatric Emergency Care Applied Research Network (PECARN)

Collaborators

TIC-TOC Collaborators of the Pediatric Emergency Care Applied Research Network (PECARN):
Marike Zwienenberg, Joseph M Galante, Sarah E Barnhard, Jordan Sandhu, Leah S Tzimentatos, Rachel M Stanley, Rajan K Thakkar, Eric A Sribnik, Kathleen K Nicol, Stephen J Fenton, Doug L Brockmeyer, Theodore J Pysher, Michael L Nance, Shih-Shan Lang Chen, Deborah A Sesok-Pizzini

Affiliations

¹ Department of Emergency Medicine, UC Davis School of Medicine, 4150 V. Street, PSSB 2100, Sacramento, CA, 95817, USA.
² Department of Pediatrics, University of Utah School of Medicine, 295 Chipeta Way, Salt Lake City, UT, 84108, USA.
³ Department of Pediatrics, Division of Pediatric Emergency Medicine, Ohio State University School of Medicine, Nationwide Children's Hospital, 700 Children's Dr, Columbus, OH, 43205, USA.
⁴ Department of Pediatrics, Division of Pediatric Emergency Medicine, University of Utah School of Medicine, Primary Children's Hospital, 100 N. Mario Capecchi Dr, Salt Lake City, UT, 84113, USA.
⁵ Department of Pediatrics, Division of Pediatric Emergency Medicine, Perelman School of Medicine, University of Pennsylvania, Children's Hospital of Philadelphia, 3401 Civic Center Blvd. Philadelphia, PA, USA, 19104.
⁶ Department of Radiology, UC Davis School of Medicine, Stockton Blvd. Sacramento, CA, 95817, USA.
⁷ Department of Pathology and Laboratory Medicine, University of California, Davis, 4400 V. Street, CA, 95816, USA.
⁸ Department of Psychology, University of California, Davis, 102K Young Hall, 1 Shields Ave. Davis, CA, 95616, USA.
⁹ Department of Pediatric Neurosciences, Neurological Institute at Phoenix Children's Hospital, 1919 E. Thomas Rd, Phoenix, AZ, 85016, USA.
¹⁰ Clinical Trials Unit, School of Hygiene and Tropical Medicine, Keppel Street, WC1E 7HT, London, UK.
¹¹ Department of Orthopedics and Rehabilitation, University of Wisconsin, 317 Knutson Drive, Madison, WI, 53704, USA.
¹² Departments of Emergency Medicine and Pediatrics, UC Davis School of Medicine, 4150 V. Street, PSSB 2100, Sacramento, CA, 95817, USA.

Abstract

Background: The antifibrinolytic drug tranexamic acid (TXA) improves survival in adults with traumatic hemorrhage; however, the drug has not been evaluated in a trial in injured children. We evaluated the feasibility of a large-scale trial evaluating the effects of TXA in children with severe hemorrhagic injuries.

Methods: Severely injured children (0 up to 18^th birthday) were randomized into a double-blind randomized trial of 1) TXA 15 mg/kg bolus dose, followed by 2 mg/kg/hr infusion over 8 hours, 2) TXA 30 mg/kg bolus dose, followed by 4 mg/kg/hr infusion over 8 hours, or 3) normal saline placebo bolus and infusion. The trial was conducted at 4 pediatric Level I trauma centers in the United States between June 2018 and March 2020. We enrolled patients under federal exception from informed consent (EFIC) procedures when parents were unable to provide informed consent. Feasibility outcomes included the rate of enrollment, adherence to intervention arms, and ability to measure the primary clinical outcome. Clinical outcomes included global functioning (primary), working memory, total amount of blood products transfused, intracranial hemorrhage progression, and adverse events. The target enrollment rate was at least 1.25 patients per site per month.

Results: A total of 31 patients were randomized with a mean age of 10.7 years (standard deviation [SD] 5.0 years) and 22 (71%) patients were male. The mean time from injury to randomization was 2.4 hours (SD 0.6 hours). Sixteen (52%) patients had isolated brain injuries and 15 (48%) patients had isolated torso injuries. The enrollment rate using EFIC was 1.34 patients per site per month. All eligible enrolled patients received study intervention (9 patients TXA 15 mg/kg bolus dose, 10 patients TXA 30 mg/kg bolus dose, and 12 patients placebo) and had the primary outcome measured. No statistically significant differences in any of the clinical outcomes were identified.

Conclusion: Based on enrollment rate, protocol adherence, and measurement of the primary outcome in this pilot trial, we confirmed the feasibility of conducting a large-scale, randomized trial evaluating the efficacy of TXA in severely injured children with hemorrhagic brain and/or torso injuries using EFIC.

Keywords: Clinical Trial; Pediatric trauma; Tranexamic Acid.

Abstract

Grants and funding