KidsDOTT-CCC

儿童DOTT-CCC

• 批准号: 9975209
• 负责人: NEIL A GOLDENBERG
• 金额: $ 40.54万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-15 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9975209
• 关键词: 21 year old; Acute; Address; Adult; Anticoagulant therapy; Anticoagulants; Anticoagulation; Biological; Blinded; Catheters; Child; Childhood; Chronic; Clinical; Clinical Research; Clinical Trials; Clinical/Radiologic; Colorado; Consensus; DNA; Data; Data Coordinating Center; Deep Vein Thrombosis; Dose; Enrollment; Evaluation; Fibrinogen; Future; Genetic Materials; Guidelines; Health Care Costs; Hemorrhage; Hospitalized Child; Hospitals; Incidence; International; Investigation; Laboratories; Malignant Neoplasms; Medical Research; Medicine; Monitor; National Heart, Lung, and Blood Institute; Neonatal; Nucleic Acids; Open Bite; Outcome; Patients; Pediatric Hospitals; Pediatrics; Phase; Placebos; Plasma; Postphlebitic Syndrome; Prognosis; Prognostic Marker; Protocols documentation; Public Health; Pulmonary Embolism; RNA; Radiology Specialty; Randomized; Randomized Clinical Trials; Randomized Controlled Trials; Recommendation; Recurrence; Research; Research Personnel; Risk; Safety; Sample Size; Specimen; Subgroup; Testing; Thrombophilia; Thrombosis; Thrombus; Time; Uncontrolled Study; Universities; Vascular Diseases; Venous; Venous Insufficiency; Venous Thrombosis; adjudicate; adjudication; base; biobank; clinical care; clinical imaging; clinical risk; clinically relevant; clinically significant; evidence based guidelines; experience; follow-up; outcome prediction; pediatric patients; programs; recruit; repository; response; secondary analysis; standard of care; stem; tertiary care; therapy duration; venous thromboembolism

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.

抽象的 近年来，儿童静脉血栓栓塞（VTE）的发病率急剧上升 年，每 200 名住院儿童中就有 1 名。每年的医疗保健费用估计为 7200 万美元 仅美国。目前国际上关于抗凝治疗持续时间的建议 儿科 VTE 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。该提案的主要目标是进行一项明确的 确定儿童静脉血栓形成抗凝持续时间的多中心随机对照试验（ 儿童-DOTI 试验）。临床协调中心是全国领先的学术医学中心之一 和研究中心，约翰霍普金斯大学，并由首席研究官领导 其独立儿科三级护理医院小儿血栓项目主任，所有 约翰霍普金斯大学医学院儿童医院。数据协调中心是大学 科罗拉多州及其附属非营利性学术研究组织 CPC 临床研究， 在血管疾病试验方面拥有丰富的 DCC 经验和独立委员会管理。这 Kids-DOTT 的主要假设是，在首次诱发急性静脉血栓的儿童中， 血栓形成，缩短抗凝持续时间（6周）同样有效，并且至少与 与常规疗程（3 个月）相比是安全的（即“不劣于”）。主要功效及 安全终点是有症状的复发性 VTE 和抗凝药物相关的、临床相关的 出血，由盲法临床终点裁定委员会裁定。审判受到监督 由指导委员会和数据与安全监测委员会组成。该研究利用 抗凝药物统一剂量和监测的国际儿科指南 在常规临床护理中，并测试特定抗凝药物的任何亚组效应 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 建立的目的是促进未来对具有良好特征的儿童的预后标志物的研究 静脉血栓形成。该试验的试点/可行性阶段是在 NHLBI K23 下启动的， 最近完成（目标样本量， 100 名患者在多中心基础上入组），这验证了关于 招募和保留，显示出放射学标准的评估者间高度可靠性 随机化，证明主要协议偏差的发生率非常低，并提供了关键 终点率的估计。

项目成果

In Children with Provoked Venous Thromboembolism, Increasing Plasma Coagulability during the First 3 Months Postdiagnosis is Prognostic of Recurrence.

• DOI: 10.1055/s-0040-1708879
• 发表时间: 2020-05
• 期刊: Thrombosis and haemostasis
• 影响因子: 6.7
• 作者: Betensky M;Mueller MG;Amankwah EK;Goldenberg NA
• 通讯作者: Goldenberg NA

Plasma fibrinolysis, inflammatory markers, and postthrombotic syndrome: preliminary findings from the Kids-DOTT Biobank.

血浆纤溶、炎症标志物和血栓后综合征：Kids-DOTT 生物库的初步发现。

• DOI: 10.1182/bloodadvances.2020002974
• 发表时间: 2021
• 期刊: Blood advances
• 影响因子: 7.5
• 作者: Betensky,Marisol;Amankwah,ErnestK;Brandal,Stephanie;Everett,AllenD;Goldenberg,NeilA
• 通讯作者: Goldenberg,NeilA