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

评估儿童氨甲环酸的创伤性临床试验 (TIC-TOC)

• 批准号: 9225008
• 负责人: NATHAN KUPPERMANN
• 金额: $ 40.53万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-01-15 至 2018-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9225008
• 关键词: 14 year old; Abdomen; Adherence; Adult; Adverse event; Advocate; Afghanistan; Anatomy; Antifibrinolytic Agents; Attenuated; Benefits and Risks; Blood Coagulation Disorders; Blood Coagulation Factor; Blood Platelets; Blood Vessels; Brain; Brain Injuries; Brain hemorrhage; Caring; Cause of Death; Cessation of life; Chest; Child; Childhood; Clinical Trials; Coagulation Process; Complex; Consent; Consumption; Critically ill children; Data; Disease; Dose; Enrollment; Evaluation; Event; Exclusion Criteria; Family; Fibrin; Fibrinolysis; Frequencies; Functional disorder; Goals; Hemorrhage; Hour; Injury; International; Intervention; Intervention Studies; Intracranial Hemorrhages; Mediating; Morbidity - disease rate; Neurocognitive; Odds Ratio; Operative Surgical Procedures; Outcome; Outcome Measure; Parents; Pathology; Patients; Pediatric Surgical Procedures; Pharmaceutical Preparations; Pharmacotherapy; Phase; Physiology; Pilot Projects; Placebos; Plasma; Plasmin; Procedures; Process; Protocols documentation; Randomized; Randomized Controlled Trials; Recruitment Activity; Research Design; Research Priority; Retrospective Studies; Risk; Safety; Seizures; Severities; Site; Therapeutic; Time; Tranexamic Acid; Transfusion; Trauma; Trauma patient; Traumatic Brain Injury; Traumatic Hemorrhage; Traumatic injury; United States; arm; base; blood product; burden of illness; control trial; disability; disability-adjusted life years; follow-up; improved; inclusion criteria; injured; mortality; pediatric trauma; phase III trial; prospective; response; standard care; success; three-arm study; traumatic event

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.

项目总结/摘要 止血药氨甲环酸（TXA）是唯一能提高成人存活率的药物治疗 受伤后严重出血。然而，TXA尚未常规用于儿童创伤性 出血，因为没有研究对受伤儿童的TXA进行了适当的评估。这样的研究， 对改善受伤儿童及其家庭的生活可能产生重大影响，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 我将通过最终进行两项大规模、多中心、随机对照试验来实现这一目标 严重受伤的儿童。一项试验将评估TXA在儿童严重受伤的身体（“躯干”） 伤害”，即，第二项试验将评估TXA在中度至中度 严重创伤性脑损伤（TBI）。然而，在重症儿童中进行临床试验具有挑战性 由于发病率较低和父母同意/子女同意程序复杂。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，但招募的患者要少得多， 评估后续两项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：两种不同的TXA剂量或安慰剂。具体 拟议的试点研究的目的是证明有能力有效地识别和登记儿童， 出血性躯干损伤或TBI纳入一项多中心、随机对照的初步研究， 剂量的TXA和安慰剂。我们将招募40名符合入选和排除标准的儿童， 参与网站为了证明收集结局指标的能力，我们将收集相同的 后续临床试验的预期结局指标：初始输注的血液制品总量 48小时护理（躯干损伤试验），前24小时内颅内出血进展， 随机化后6个月的神经认知功能（TBI试验）。我们还将收集安全性结果， 特别是静脉血栓栓塞事件（即，在最初的24小时内， 小时的研究药物。这项初步研究的其他目的是：评价有效筛选的能力， 在损伤后3小时内确定、同意、随机化并开始研究干预，评估方案 入组患者的护理依从性和可变性，并确定运营效率， 提高后续试验的成功率。