Prospective Multi-Center Evaluation of the Duration of Therapy for Thrombosis in Children
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 532
- 试验地点
- 120
- 主要终点
- Efficacy Outcome - Occurrence of Symptomatic Recurrent Venous Thromboembolism
研究概览
简要总结
The Kids-DOTT trial is a randomized controlled clinical trial whose primary objective is to evaluate non-inferiority of shortened-duration (6 weeks) versus conventional-duration (3 months) anticoagulation in children with first-episode acute venous thrombosis. The first stage of the trial has consisted of a pilot/feasibility component, which then continues as the definitively-powered trial.
详细描述
Children (birth to 21 years of age, inclusive) with first-episode venous thrombosis in association with a reversible clinical trigger (key exclusions: history of cancer; severe thrombophilia state disclosed) are enrolled and prescribed anticoagulation according to the clinical standard of care and American College of Physicians (Chest journal) 2012 recommendations. At the 6 week (post-diagnosis) follow-up visit, repeat radiologic imaging is performed to determine residual thrombus burden and its degree of occlusion. In addition, those subjects with antiphospholipid antibodies (APA) disclosed at enrollment will undergo repeat APA testing.
Patients with residual occlusive thrombosis or persistent APA are excluded from randomization, and followed on parallel cohort arms (observational), with conventional anticoagulation durations. All other patients are randomized to a total anticoagulant duration of 6 weeks versus 3 months. Children are followed for primary efficacy endpoints of symptomatic recurrent venous thromboembolism (VTE) and primary safety endpoints of clinically-relevant bleeding (major plus clinically-relevant non-major, as per International Society of Thrombosis and Haemostasis Scientific and Standardization Committee [Journal of Thrombosis & Haemostasis] 2012 definitions/recommendations).
Children are followed through 2 years (with primary endpoint at 1 year). Those with deep venous thromboses affecting venous return from the limbs also undergo standardized post-thrombotic syndrome (PTS) outcome assessment using the Manco-Johnson pediatric PTS instrument.
The non-inferiority analysis uses a bivariate endpoint approach, modeling the inherent clinical trade-off between the risks of recurrent VTE and bleeding. The trial will enroll 750 children across 40 participating centers, and allows for a 25% rate of exclusion from the per-protocol population due to randomization non-eligibility (i.e. parallel cohort), withdrawal/loss to follow-up, and protocol non-adherence.
A sub-study, completed in late 2013, used investigational dalteparin in lieu of formulary low molecular weight heparin (typically enoxaparin) in those children who were clinically prescribed a low molecular weight heparin for sub-acute anticoagulation. The goal of this sub-study was to report dose-finding and outcomes data in children treated with dalteparin for VTE. Outcomes in these patients were qualitatively compared with those of patients who received enoxaparin, warfarin, or other anticoagulants for sub-acute anticoagulation. This portion of the study was an industry-sponsored investigator-initiated sub-study with an investigator-held IND. Since the closure of the sub-study, the overall Kids-DOTT study is no longer conducted under an Investigational New Drug (IND) application.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- — 至 20 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Children (birth to <21 years of age) with radiologically-confirmed acute deep venous thrombosis in the past 30 days
- •In the opinion of the investigator, the venous thrombosis was a provoked (i.e., non-spontaneous) event (e.g.: hospitalization; Central venous catheterization; infection; dehydration; surgery; trauma; immobility; use of estrogen-containing oral contraceptive pills; flare of autoimmune/rheumatologic condition).
排除标准
- •Prior episode of VTE
- •Malignancy that, in the opinion of the treating oncologist, is not in remission (note: remission may exist on or off anti-neoplastic therapy)
- •Systemic lupus erythematosus
- •Pulmonary embolism that is not accompanied by DVT or is more proximal than segmental branches of the pulmonary artery
- •Use of, or intent to use, thrombolytic therapy
- •Chronic anticoagulant at prophylactic dosing is being or will be administered beyond 6 months post VTE diagnosis
- •Moderate/severe anticoagulant deficiency (defined by any one of the following):
- •protein C <20 IU/dL if patient is ≥3 months of age, or protein C below lower limit of detection if patient is <3 months of age;
- •antithrombin <30 IU/dL if patient is ≥3 months of age, or antithrombin below lower limit of detection if patient is <3 months of age;
- •protein S (free antigen or activity) <20 IU/dL.
结局指标
主要结局
Efficacy Outcome - Occurrence of Symptomatic Recurrent Venous Thromboembolism
时间窗: 1 Year
Occurrence of symptomatic recurrent venous thromboembolism. Primary safety endpoint is occurrence of clinically-relevant bleeding (major + clinically-relevant non-major) bleeding.
Safety Outcome - Occurrence of Clinically-relevant (i.e. Major Plus Clinically-relevant Non-major (CRNM)
时间窗: 1 year
Occurrence of clinically-relevant (i.e. major plus clinically-relevant non-major (CRNM) bleeding
次要结局
- Efficacy Outcome 1 - Occurrence of Symptomatic Recurrent Venous Thromboembolism (VTE) or Development of Post Thrombotic Syndrome (PTS) (Composite Endpoint)(1 year)
- Efficacy Outcome 2 - Occurrence of Symptomatic Recurrent Venous Thromboembolism (VTE)(2 years)
- Efficacy Outcome 3 - Development of Post Thrombotic Syndrome (PTS)(1 year)