KidsDOTT-CCC

摘要 近年来，儿童静脉血栓栓塞症（VTE）的发病率急剧增加 每200名住院儿童中就有1人死亡。每年的医疗保健费用估计为7200万美元， 美国一个人目前国际上对抗凝治疗持续时间的建议 儿童VTE是基于成人随机对照试验（RCT）的结果，但呼吁 用于专门的儿科试验本提案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抗凝治疗的持续时间（ Kids-DOTI试验）。临床协调中心是全国领先的学术医疗中心之一， 和研究中心，约翰霍普金斯大学，并由首席研究官和 儿科血栓项目主任，其独立的儿科三级保健医院，所有 儿童医院约翰霍普金斯医学。数据协调中心是大学 科罗拉多及其附属的非营利性学术研究组织CPC临床研究， 在血管疾病试验中具有丰富的DCC经验和独立委员会管理。的 Kids-DOTT的主要假设是，在第一次发作急性静脉炎的儿童中， 血栓形成，缩短抗凝持续时间（6周）同样有效，至少 安全（即，“非劣效性”），与常规持续时间治疗（3个月）相比。主要有效性和 安全性终点为症状性复发性VTE和抗凝剂依赖性，临床相关 出血，由设盲临床终点裁定委员会裁定。审判受到监督 指导委员会和数据与安全监测委员会。该研究利用了 国际儿科抗凝剂统一剂量和监测指南 在常规的临床护理中，以及在一个特定的抗凝药物的任何亚组效应的测试中， 次要目标。作为另一个目标，将建立一个血浆和遗传物质的试验生物储存库。 建立，以促进未来的研究预后标志物的良好特征的儿童， 静脉血栓试验的试点/可行性阶段是根据NHLBI K23启动的， 最近完成（目标样本量， 100例患者在多中心基础上入组），其已验证了关于 招募和保留，显示放射学标准的高评分者间可靠性， 随机化，证明了重大方案偏离率非常低，并提供了关键 终点发生率的估计值。

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.