Department of Pharmacy, Children's Healthcare of Atlanta, Atlanta, Georgia.
Department of Pharmacy, The Johns Hopkins All Children's Hospital, St. Petersburg, Florida.
Semin Thromb Hemost. 2021 Sep;47(6):643-653. doi: 10.1055/s-0041-1725944. Epub 2021 May 10.
Venous thromboembolism (VTE) in children can lead to significant morbidity and mortality. Traditionally, treatment for thrombotic events in pediatric patients has been limited mainly to unfractionated heparin, low-molecular-weight heparin (LMWH), or vitamin K antagonists. Since the first non-vitamin K antagonist oral anticoagulant (NOAC) was approved for adult use, these agents have gained popularity for a variety of indications. This is largely due to their ease of administration, favorable pharmacokinetic and pharmacodynamic profile, decreased food interactions, and decreased need for therapeutic drug monitoring. Treating and preventing VTE with traditional anticoagulants in pediatric patients presents many challenges. This systematic review evaluated the current literature regarding pediatric NOAC trials. Additionally, based on an up-to-date query of , we detail current ongoing and as-yet unpublished clinical trials, study outcomes, and projected completion dates. Published pediatric NOAC trials have included 1,007 total children to date and have ranged from phase 1 to 4, with "indications" including both thromboembolism prophylaxis and VTE treatment. Three recent phase 3 trials, specifically involving rivaroxaban and dabigatran, have shown the agents to be at least as effective as traditional anticoagulants for acute and/or extended VTE treatment, with low frequency of recurrent thrombosis and clinically significant bleeding rates. Additionally, specially developed and tested pediatric formulations have allowed for accurate and reliable dosing, oral administration, stable pharmacokinetics and pharmacodynamics, and fewer drug or food interactions. Ongoing trials, anticipated for completion in the next few years, will reveal important information with regard to thromboembolism prophylaxis in special pediatric subpopulations and settings.
儿童静脉血栓栓塞症（VTE）可导致严重的发病率和死亡率。传统上，小儿血栓事件的治疗主要限于未分级肝素、低分子量肝素（LMWH）或维生素 K 拮抗剂。自第一个非维生素 K 拮抗剂口服抗凝剂（NOAC）获准用于成人后，这些药物因其易于管理、良好的药代动力学和药效学特征、减少食物相互作用以及减少治疗药物监测的需要而在各种适应症中广受欢迎。使用传统抗凝剂治疗和预防小儿 VTE 存在许多挑战。本系统评价评估了目前关于儿科 NOAC 试验的文献。此外，根据对 的最新查询，我们详细介绍了目前正在进行和尚未发表的临床试验、研究结果和预计完成日期。迄今为止，已发表的儿科 NOAC 试验共纳入了 1007 名儿童，范围从 1 期到 4 期，“适应症”包括血栓栓塞预防和 VTE 治疗。最近的三项 3 期试验，特别是涉及利伐沙班和达比加群的试验，表明这些药物在急性和/或延长 VTE 治疗方面至少与传统抗凝剂一样有效，且血栓复发率低，临床显著出血率低。此外，专门开发和测试的儿科配方允许进行准确可靠的剂量、口服给药、稳定的药代动力学和药效学以及较少的药物或食物相互作用。预计在未来几年内完成的正在进行的试验将揭示有关特殊儿科亚人群和环境中血栓栓塞预防的重要信息。
