Nishijima Daniel K, VanBuren John M, Linakis Seth W, Hewes Hilary A, Myers Sage R, Tran Nam K, Ghetti Simona, Bobinski Matthew, Adelson P David, Roberts Ian, Holmes James F, Schalick Walton O, Dean J Michael, Casper T Charles, Kuppermann Nathan
Department of Emergency Medicine, UC Davis School of Medicine, Sacramento, California, USA.
Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, Utah, USA.
Acad Emerg Med. 2022 Jul;29(7):862-873. doi: 10.1111/acem.14481. Epub 2022 Apr 8.
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.
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.
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.
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.
抗纤维蛋白溶解药物氨甲环酸（TXA）可提高创伤性出血成人患者的生存率；然而，该药物尚未在受伤儿童的试验中进行评估。我们评估了一项大规模试验的可行性，该试验旨在评估TXA对严重出血性损伤儿童的影响。
将严重受伤儿童（0至18岁生日）随机分为双盲随机试验，分别给予（1）TXA 15mg/kg静脉推注剂量，随后8小时内以2mg/kg/h的速度输注；（2）TXA 30mg/kg静脉推注剂量，随后8小时内以4mg/kg/h的速度输注；或（3）生理盐水安慰剂推注和输注。该试验于2018年6月至2020年3月在美国的四个儿科一级创伤中心进行。当父母无法提供知情同意时，我们根据联邦知情同意豁免程序（EFIC）招募患者。可行性结果包括入组率、对干预组的依从性以及测量主要临床结局的能力。临床结局包括整体功能（主要指标）、工作记忆、输注血液制品的总量、颅内出血进展情况以及不良事件。目标入组率为每个站点每月至少1.25名患者。
共有31名患者被随机分组，平均年龄为10.7岁（标准差[SD]5.0岁），22名（71%）患者为男性。从受伤到随机分组的平均时间为2.4小时（SD 0.6小时）。16名（52%）患者有孤立性脑损伤，1
