Traumatic Injury Clinical Trial Evaluating Tranexamic Acid in Children (TIC-TOC)

项目摘要/摘要 氨甲环酸(TXA)是一种止血药物，是唯一能提高成人存活率的药物。 受伤后有严重出血。然而，TXA并未被常规用于患有创伤的儿童 出血是因为没有研究适当地评估受伤儿童的TXA。这样的研究具有 可能对改善受伤儿童及其家人的生活产生重大影响，如果发现 成功。我们的长期目标是评估TXA在严重受伤儿童中的益处和风险。我们 最终将通过对TXA的使用进行两项大规模、多中心、随机对照试验来实现这一点 在严重受伤的儿童中。一项试验将评估患有严重身体损伤(躯干)的儿童的TXA 损伤“，即腹部和胸部)，第二个试验将评估血栓素A在中度到 重型颅脑损伤(TBI)。然而，在危重儿童身上进行临床试验是具有挑战性的。 由于发病率较低和复杂的父母同意/子女同意程序。因此，我们建议 在这里进行一项试点研究，设计类似于全面试验，但患者登记人数要少得多， 评估随后两个大规模临床试验的可行性，并填补关键的信息空白。我们 将受伤的儿童随机分为三组：两种不同剂量的TXA或安慰剂。具体的 拟议的试点研究的目的是证明有能力有效地识别和登记患有 一项评估这两种损伤的多中心随机对照先导研究 剂量的血栓素A和安慰剂。我们将招收40名符合纳入和排除标准的儿童 参与站点。为了展示收集结果度量的能力，我们将收集相同的 后续临床试验的预期结果衡量标准：初始阶段输血的总产血量 48小时护理(躯干损伤试验)，以及前24小时和 随机化后6个月的神经认知功能(TBI试验)。我们还将收集安全成果， 特别是静脉血栓栓塞症(即，血管中的血栓)和最初24小时内的癫痫发作 几个小时的药物学习。这项试点研究的其他目标是：评估有效筛查的能力， 在受伤后3小时内确定、同意、随机化并启动研究干预，评估方案 登记患者的护理依从性和可变性，并确定运营效率与潜在的 加强后续试验的成功。

PROJECT SUMMARY/ABSTRACT Tranexamic acid (TXA), a drug that stops bleeding, is the only drug treatment that improves survival in adults with serious bleeding after injuries. However, TXA has not been used routinely in children with traumatic bleeding because no studies have appropriately evaluated TXA for injured children. Such a study has the potential for significant impact in improving the lives of injured children and their families, if found to be successful. Our long-term objective is to evaluate the benefits and risks of TXA in severely injured children. We will achieve this by ultimately conducting two large-scale, multicenter, randomized controlled trials of TXA use in severely injured children. One trial will evaluate TXA in children with severe injuries to the body (“torso injuries”, i.e., to the abdomen and chest) and the second trial will evaluate TXA in children with moderate-to- severe traumatic brain injuries (TBIs). However, conducting a clinical trial in critically ill children is challenging due to lower disease frequency and complex parent consent/child assent procedures. We therefore propose here to conduct a pilot study, designed similarly to the full-scale trials but with much smaller patient enrollment, to assess the feasibility of, and fill crucial information gaps for the two subsequent large-scale clinical trials. We will randomize injured children to one of three study arms: two different TXA doses or placebo. The specific aim of the proposed pilot study is to demonstrate the ability to efficiently identify and enroll children with hemorrhagic torso injuries or TBIs into a multicenter, randomized controlled pilot study evaluating these two doses of TXA and placebo. We will enroll 40 children who meet inclusion and exclusion criteria at 4 participating sites. To demonstrate the ability to collect outcome measures, we will collect the identical anticipated outcome measures for the subsequent clinical trials: total blood products transfused over the initial 48 hours of care (torso injury trial), and intracranial hemorrhage progression in first 24 hours and neurocognitive function at 6 months after randomization (TBI trial). We will also collect safety outcomes, specifically venothromboembolic events (i.e., blot clots in the blood vessels) and seizures within the initial 24 hours of study drug. Additional objectives of this pilot study are to: evaluate the ability to efficiently screen, identify, consent, randomize, and initiate the study intervention within 3 hours of injury, assess protocol adherence and variability of care in enrolled patients, and identify operational efficiencies with the potential to enhance the success of the subsequent trials.