Clinical Investigation in Pediatric Thrombosis

描述（由申请人提供）：随着重症儿童护理和侵入性管理的进步，静脉血栓栓塞在过去十年中在儿科中得到越来越多的认识。儿童血栓形成的最佳治疗需要熟练评估急性和长期血栓形成倾向、不良血栓后outpomes风险和潜在出血并发症。迄今为止，通过血栓形成/血栓形成倾向领域和临床研究学科的正式指导培训获得专业知识的儿科亚专科医生数量有限，其中许多人在职业生涯中处于高级地位。与此同时，很少有随机对照试验（RCT）为儿童血栓形成的管理提供临床证据，指南主要基于成人数据。考虑到这些关键的公共卫生需求，本提案的主要目的是为申请人提供儿科血栓形成/血栓形成倾向和临床/转化研究方面的特殊指导培训，并促进其在进行基于网络的原始RCT的试点/可行性研究中的指导作用（由以下网络支持并通过以下网络执行，血友病和血栓形成研究协会），该研究旨在优化儿童静脉血栓形成抗凝治疗的持续时间。本研究的主要假设是，在发生早期血栓消退且临床和实验室特征构成血栓后不良结局低风险的急性静脉血栓形成儿童中，缩短抗凝持续时间与常规抗凝持续时间一样有效，至少同样安全。入组的儿童将根据当前标准治疗进行急性抗凝治疗; 6周时经放射学检查显示血栓消退的患者将被随机分配至不接受进一步抗凝治疗或完成常规3个月疗程。患者将随访2年，对出血并发症、复发性血栓栓塞和血栓后综合征进行统一评估，以初步比较两种方案的安全性和疗效。在10个试点研究中心入组200例患者将为未来的确定性RCT提供足够的试点数据，并证明其可行性。此外，翻译研究将寻求确定新的候选蛋白质的风险因素和预后标志物的静脉血栓形成的儿童。

DESCRIPTION (provided by applicant): With advances in the care and invasive management of critically ill children, venous thromboembolism has become increasingly recognized in pediatrics over the past decade. Optimal treatment of thrombosis in children requires a skilled assessment of acute and long-term prothrombotic tendencies, risk of adverse post-thrombotic outpomes, and potential hemorrhagic complications. To date, the number of pediatric subspecialists who have gained expertise through formal mentored training in both the field of thrombosis/ thrombophilia and the discipline of clinical investigation is limited, and many of these individuals are senior in their careers. At the same time, few randomized controlled trials (RCTs) have provided clinical evidence for the management of thrombosis in children, and guidelines remain largely based upon adult data. Given these critical public health needs, the PRINCIPAL OBJECTIVE of this proposal is to provide the applicant with exceptional mentored training in pediatric thrombosis/thrombophilia and clinical/translational research, and to foster his mentored role in conducting a pilot/feasibility study for an original, web-based RCT (supported by, and performed via the network of, the Hemophilia and Thrombosis Research Society) that seeks to optimize the duration of anticoagulant therapy for venous thrombosis in children. The PRIMARY HYPOTHESIS of the study is that a shortened duration of anticoagulation is as effective, and at least as safe, as conventional-duration anticoagulation in children with acute venous thrombosis in whom early thrombus resolution has occurred and clinical and laboratory features constitute a low-risk for adverse post- thrombotic outcomes. Enrolled children will be treated acutely with anticoagulation according to the present standard of care; patients who demonstrate thrombus resolution radiologically at 6 weeks will then be randomized to undergo no further anticoagulation versus to complete a conventional 3-month course of therapy. Patients will be followed for 2 years with uniform assessment of bleeding complications, recurrent thromboembolism, and the post-thrombotic syndrome, for preliminary safety and efficacy comparison between the two regimens. Enrollment of 200 patients across 10 pilot sites will provide sufficient pilot data for, and demonstrate the feasibility of, the future definitive RCT. Additionally, translational studies will seek to identify novel candidate protein risk factors and prognostic markers for venous thrombosis in children.