Clinical Investigation in Pediatric Thrombosis

描述(申请人提供)：在过去的十年里，随着危重儿童的护理和侵入性治疗的进步，静脉血栓栓塞症在儿科得到了越来越多的认可。儿童血栓形成的最佳治疗需要熟练地评估急性和长期血栓前倾向、血栓后不良反应的风险和潜在的出血性并发症。迄今为止，通过正规的指导培训获得血栓形成/血栓形成和临床调查学科方面专门知识的儿科专家人数有限，而且其中许多人都是职业生涯中的资深人士。与此同时，很少有随机对照试验(RCT)为儿童血栓形成的治疗提供临床证据，指南仍然主要基于成人数据。鉴于这些关键的公共卫生需求，这项建议的主要目标是为申请人提供儿科血栓形成/血栓形成和临床/翻译研究方面的特殊指导培训，并促进其在进行原创的、基于网络的随机对照试验/可行性研究(由血友病和血栓形成研究会支持并通过其网络进行)方面的指导作用，该试验旨在优化儿童静脉血栓的抗凝治疗持续时间。这项研究的主要假设是，在急性静脉血栓形成的儿童中，较短的抗凝时间与常规持续时间的抗凝一样有效，至少同样安全，因为在这些儿童中，早期血栓已经消退，临床和实验室特征构成血栓后不良结果的低风险。根据目前的护理标准，登记的儿童将接受急性抗凝治疗；6周后放射学显示血栓消失的患者将被随机分组，不再接受进一步的抗凝治疗，而不是完成常规的3个月疗程。将对患者进行为期两年的统一评估，以评估出血并发症、再发血栓栓塞症和血栓后综合征，以初步比较两种方案的安全性和有效性。在10个试点招募200名患者，将为未来最终的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儿童静脉血栓形成的新的候选蛋白风险因素和预后标记物。

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.