Goldenberg Neil A, Schulman Sam, Kittelson John M, Abshire Thomas C, Casella James F, Dale Rita, Halperin Jonathan L, Hanson Jade, Kessler Craig M, Manco-Johnson Marilyn J, McDevitt Laurel, Sidonio Robert F, Spyropoulos Alex C, Steg P Gabriel, Bonaca Marc P
Johns Hopkins All Children's Institute for Clinical and Translational Research, Johns Hopkins All Children's Hospital, St. Petersburg, Florida, USA; Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Department of Medicine, Thrombosis and Atherosclerosis Research Institute, McMaster University, Hamilton, Ontario, Canada; Department of Cardiology, Obstetrics and Gynecology and Perinatal Medicine, I.M. Sechenov First Moscow State Medical University, Moscow, Russia.
J Thromb Haemost. 2025 Feb;23(2):651-656. doi: 10.1016/j.jtha.2024.09.038. Epub 2024 Oct 24.
The Multicenter Evaluation of the Duration of Therapy for Thrombosis in Children multinational, randomized clinical trial revealed noninferiority of a 6-week vs 3-month duration of anticoagulation for the treatment of provoked venous thromboembolism (VTE) in patients <21 years old in regard to net clinical benefit at 1 year.
To evaluate noninferiority at 2 years.
Patients whose repeat imaging 6 weeks after VTE diagnosis did not show complete veno-occlusion were randomized to discontinue anticoagulation vs receive a total 3-month course and followed for 2 years for the occurrence of symptomatic recurrent VTE (efficacy outcome) and clinically relevant bleeding (safety outcome). Outcomes were centrally adjudicated, and net clinical benefit was compared between treatment arms via a prespecified bivariate noninferiority boundary, using 95% CIs in absolute risk differences between treatment arms.
Kaplan-Meier estimates of 2-year cumulative incidences in the 6-week and 3-month arms of the intention-to-treat population (n = 417) were 1.7% (95% CI, 0%, 3.7%) and 2.9% (95% CI, 0.3%, 5.4%), respectively, for symptomatic recurrent VTE and 1.1% (95% CI, 0%, 2.5%) and 3.2% (95% CI, 0.6%, 5.7%), respectively, for clinically relevant bleeding. Bivariate analysis of the absolute risk differences in the intention-to-treat population demonstrated that a 6-week anticoagulation duration was noninferior to a 3-month course.
These findings support durability of the Kids-DOTT randomized clinical trial findings of net clinical benefit at 2 years.
儿童血栓形成治疗持续时间的多中心评估这一跨国随机临床试验表明，在1年的净临床获益方面，对于21岁以下因诱因导致的静脉血栓栓塞（VTE）患者，6周抗凝疗程不劣于3个月抗凝疗程。
评估2年时的非劣效性。
VTE诊断6周后重复成像未显示完全静脉闭塞的患者被随机分为停止抗凝组与接受总计3个月疗程组，并随访2年，观察有症状的复发性VTE（疗效结局）和临床相关出血（安全性结局）的发生情况。结局由中心判定，并通过预设的双变量非劣效性边界比较治疗组之间的净临床获益，使用治疗组之间绝对风险差异的95%置信区间。
在意向性治疗人群（n = 417）中，6周组和3个月组2年累积发生率的Kaplan-Meier估计值显示，有症状的复发性VTE分别为1.7%（95% CI，0%，3.7%）和2.9%（95% CI，0.3%，5.4%），临床相关出血分别为1.1%（95% CI，0%，2.5%）和3.2%（95% CI，0.6%，5.7%）。在意向性治疗人群中对绝对风险差异进行双变量分析表明，6周抗凝疗程不劣于3个月疗程。
这些发现支持了Kids-DOTT随机临床试验在2年时净临床获益的研究结果具有持续性。
