KidsDOTT-DCC

摘要 近年来，静脉血栓栓塞症(VTE)在儿童中的发病率急剧上升，达到每200名住院儿童中就有一名。仅在美国，每年的医疗费用估计就高达7200万美元。目前国际上对儿童静脉血栓栓塞术抗凝治疗持续时间的建议是基于成人随机对照试验(RCT)的结果，但呼吁进行专门的儿科试验。这项建议的主要目标是进行一项明确的多中心随机对照试验，以确定儿童静脉血栓形成的抗凝持续时间(Kids-Doti试验)。临床协调中心是美国领先的学术医疗和研究中心之一，约翰霍普金斯大学，由其独立的儿科三级护理医院-所有儿童医院约翰·霍普金斯医学-的首席研究官和儿科血栓形成项目主任领导。数据协调中心是科罗拉多大学及其附属的非营利性学术研究组织CPC临床研究，该组织在血管疾病试验方面拥有丰富的DCC经验和独立的委员会管理。Kids-Dott的基本假设是，在首次引发急性静脉血栓形成的儿童中，较短的抗凝时间(6周)与传统持续时间(3个月)的抗凝治疗一样有效，至少也一样安全(即“非劣质”)。主要的疗效和安全终点是有症状的复发性静脉血栓栓塞症和抗凝剂相关的临床相关出血，由盲目的临床终点裁决委员会裁决。这项试验由一个指导委员会和一个数据和安全监测委员会监督。这项研究利用了国际儿科指南，对常规临床护理中使用的抗凝剂进行统一剂量和监测，并在次要目标中测试特定抗凝剂的任何亚组效果。作为另一个目标，将建立一个血浆和遗传物质的试验性生物库，以促进未来对具有良好特征的静脉血栓形成儿童的预后标志物的研究。试验的试点/可行性阶段在NHLBI K23下启动，最近完成(目标样本量， 100名患者在多中心基础上登记)，它验证了关于招募和保留的假设，显示了随机放射学标准在评价者之间的高可靠性，显示了非常低的重大方案偏差率，并提供了终止率的关键估计。

ABSTRACT The incidence of venous thromboembolism (VTE) has dramatically increased in children in recent years, to 1 in 200 hospitalized children. Annual health care costs can be estimated at $72M in the U.S. alone. Current international recommendations for duration of anticoagulant therapy in pediatric VTE are based upon findings of randomized controlled trials (RCTs) in adults, but call for devoted pediatric trials. The PRINCIPAL OBJECTIVE of this proposal is to conduct a definitive multicenter RCT to establish the duration of anticoagulation for venous thrombosis in children (the Kids-DOTI trial). The Clinical Coordinating Center is one of the nation's leading academic medical and research centers, Johns Hopkins University, and is led by the Chief Research Officer and Pediatric Thrombosis Program Director of its stand-alone pediatric tertiary care hospital, All Children's Hospital Johns Hopkins Medicine. The Data Coordinating Center is the University of Colorado and its affiliated non-profit Academic Research Organization CPC Clinical Research, which has extensive DCC experience and independent committee management in vascular disease trials. The PRIMARY HYPOTHESIS of Kids-DOTT is that, in children with a first episode of provoked acute venous thrombosis, a shortened duration of anticoagulation (6 weeks) is just as effective, and at least as safe (i.e., "non-inferior"), to conventional-duration therapy (3 months). The primary efficacy and safety endpoints are symptomatic recurrent VTE and anticoagulant­ associated, clinically-relevant bleeding, adjudicated by a blinded Clinical Endpoint Adjudication Committee. The trial is overseen by a Steering Committee and a Data and Safety Monitoring Committee. The research takes advantage of international pediatric guidelines for uniform dosing and monitoring of anticoagulants administered in routine clinical care, and tests for any subgroup effects of specific anticoagulant drugs in a secondary aim. As an additional aim, a trial biorepository of plasma and genetic material will be established to faciliate future research on prognostic markers in well-characterized children with venous thrombosis. The pilot/feasibility phase of the trial was initiated under an NHLBI K23 and recently completed (target sample size, 100 patients enrolled on a multicenter basis), which has validated assumptions regarding recruitment and retention, shown high inter-rater reliability of radiologic criteria for randomization, demonstrated a very low rate of major protocol deviations, and provided key estimates on endpoint rates.