Pediatric Severe Traumatic Brain Injury in Latin America – A Randomized Trial Comparing Two Management Protocols

摘要 严重创伤性脑损伤（sTBI）幸存的儿童生活在深刻的损伤中， 发展和未来的可能性。在世界范围内，TBI是儿童死亡和残疾的主要原因 和青少年。在美国，儿童TBI的年发病率高于MS，HIV/AIDS，脊髓损伤， 损伤和乳腺癌合并1。虽然不是严格意义上的儿科疾病，但这种比较说明了 我们正在处理的全球儿科健康流行病的规模和重要性。 我们科学研究的主要重点是进行高质量的随机对照试验 解决一个关键的TBI管理问题：使用一个包含颅内压信息的方案 (ICP)监测以直接治疗sTBI儿童与积极管理相比可改善结局 仅基于成像和临床检查的方案？我们的成人ICP研究2发现， 结果差异，并促使重新思考sTBI患者的治疗指南>13。单独的 研究是必要的，因为儿童不仅仅是小的成年人，一些治疗方法与年龄有关， 额外的风险。因此，研究结果将为美国和全球临床实践提供信息。 本试验将在7个拉丁美洲儿科ICU进行，这些ICU的基础设施和实践模式 最佳的强大的内部有效性和资源代表创伤护理在发展中国家。成功 青少年/成人BEST TRIP试验，在类似环境中收集高质量数据（引用> 900次） 强调了这种方法的可行性。 具体目的：在一项III期随机优效性试验中，纳入了来自7个拉丁美洲儿童的428名sTBI儿童 创伤中心，测试由使用来自以下信息的协议指导的sTBI管理结果的影响： ICP监测与使用成像和临床检查指导治疗的方案进行管理。 假设#1：使用基于数据的方案管理急性护理治疗的重度TBI儿童 在6个月时，ICP监测的死亡率显著降低，生活质量和总体结局改善 创伤后比那些治疗是基于成像和临床检查的协议管理。 功能恢复的主要指标是6个月时的PedsQL。第二种方法是GOSE-Peds。 假设2：将ICP监测纳入sTBI患者护理将最大限度地减少继发性并发症， 减少在ICU的停留时间，减少脑部特异性治疗。 具体目标：我们将培训新研究中心的人员如何进行高质量的科学研究， 并将扩大与我们合作的人员的培训，巩固以前的能力- 努力，并开始新的努力。

Abstract Children who survive severe traumatic brain injury (sTBI) live with profound impairments that alter their development and future possibilities. Worldwide, TBI is the leading cause of death and disability among children and adolescents. In the US, the annual incidence of pediatric TBI is greater than MS, HIV/AIDS, spinal cord injury, and breast cancer combined1. Although not strictly pediatric diseases, this comparison illustrates the magnitude and importance of the pediatric global health epidemic we are addressing. Our primary focus for scientific investigation is to conduct a high quality randomized controlled trial addressing a critical TBI management question: Does using a protocol with information from intracranial pressure (ICP) monitoring to direct treatment of children with sTBI improve outcomes vs an aggressive management protocol based on imaging and clinical examination alone? This follows on our adult ICP study2 which found no outcome differences and has occasioned re-thinking of treatment guidelines for sTBI patients >13. A separate study is essential because children are not simply small adults and some treatment approaches carry age-related additional risks. Thus, study findings will inform US and global clinical practice. This trial will be conducted in 7 Latin American pediatric ICUs where infrastructures and practice patterns are optimal for strong internal validity and resources represent trauma care in the developing world. The successful adolescent/adult BEST TRIP trial, which collected high-quality data in similar environments (cited > 900 times) underscores the feasibility of this approach. Specific Aim: In a Phase III randomized superiority trial in 428 children with sTBI from 7 Latin American pediatric trauma centers, test the effect on outcomes of management of sTBI guided by a protocol using information from ICP monitors vs. management using a protocol that uses imaging and clinical exams to guide treatment. Hypothesis #1: Children with severe TBI whose acute care treatment is managed using a protocol based on data from ICP monitoring will have significantly lower mortality and better quality of life and global outcome at 6 months post-trauma than those whose treatment is managed with a protocol based on imaging and clinical exam. The primary measure of functional recovery is the PedsQL at 6 months. A secondary measure is GOSE-Peds. Hypothesis #2: Incorporating ICP monitoring into sTBI patient care of will minimize secondary complications, decrease length of stay in ICU and decrease brain-specific treatments. Specific Aim: We will train personnel in centers new to research in how to conduct high-quality scientific studies, and will extend the training for the personnel with whom we have been working, solidifying previous capacity- building efforts, and initiating new efforts.