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

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 assessed 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 18th birthday) were randomized into a double-blind randomized trial of (1) TXA 15 mg/kg bolus dose, followed by 2 mg/kg/h infusion over 8 h, (2) TXA 30 mg/kg bolus dose, followed by 4 mg/kg/h infusion over 8 h, or (3) normal saline placebo bolus and infusion. The trial was conducted at four 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 h (SD 0.6 h). 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 (nine 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.

Automated summary

This study assessed the feasibility of using the antifibrinolytic drug tranexamic acid (TXA) to treat hemorrhagic brain and/or torso injuries in severely injured children. The trial confirmed the possibility of conducting a large-scale trial using federal exception from informed consent (EFIC) procedures to evaluate the efficacy of TXA in children.