Children with cardiac diseases suffer from significant morbidity and mortality secondary to thromboembolic complications. Anticoagulant agents currently used for thromboprophylaxis have many limitations, including subcutaneous administration (low molecular weight heparins) and requirement for frequent monitoring via venipuncture (vitamin K antagonists). Edoxaban is an oral direct factor Xa inhibitor without need of monitoring. In the treatment of venous thromboembolism in adults, edoxaban has shown to be effective and safe.This manuscript summarises the rationale and design of a phase 3, open-label, randomised controlled trial to evaluate and compare the safety and efficacy of edoxaban against standard of care (namely, vitamin K antagonist and low molecular weight heparin) in children with cardiac diseases.A goal of 150 children with cardiac diseases at risk of thromboembolic complications who need primary or secondary anticoagulant prophylaxis will be recruited. Eligible children between 6 months and <18 years of age will be randomised in a ratio of 2 to 1 for edoxaban versus standard of care. Randomisation will be stratified based on underlying cardiac disease and concomitant use of aspirin for patients other than Kawasaki disease. The primary outcome will be safety, comprised of major and clinically relevant non-major bleeding in first 3 months of treatment. Bleeding beyond 3 months, symptomatic and asymptomatic thromboembolic events, and pharmacokinetic and pharmacodynamic parameters will be evaluated as secondary outcomes.Randomised controlled anticoagulation trials are challenging in children. This study will evaluate a potentially valuable alternative of oral anticoagulant prophylactic use in children with cardiac diseases.

中文翻译：

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ENNOBLE-ATE 试验：一项开放标签、随机、多中心、观察性研究，用于治疗有血栓栓塞风险的心脏病儿童

患有心脏病的儿童患有血栓栓塞并发症继发的显着发病率和死亡率。目前用于血栓预防的抗凝剂有许多局限性，包括皮下给药（低分子量肝素）和需要通过静脉穿刺进行频繁监测（维生素 K 拮抗剂）。Edoxaban 是一种口服直接 Xa 因子抑制剂，无需监测。在成人静脉血栓栓塞的治疗中，艾多沙班已被证明是有效和安全的。本手稿总结了一项 3 期、开放标签、随机对照试验的基本原理和设计，以评估和比较艾多沙班与标准的安全性和有效性。心脏病患儿的护理（即维生素K拮抗剂和低分子肝素）。将招募 150 名有血栓栓塞并发症风险且需要初级或二级抗凝剂预防的心脏病儿童。符合条件的 6 个月至 <18 岁的儿童将按 2 比 1 的比例随机分配艾多沙班与标准护理。随机分组将根据潜在的心脏病和对川崎病以外的患者同时使用阿司匹林进行分层。主要结果将是安全性，包括治疗前 3 个月的主要和临床相关的非主要出血。超过 3 个月的出血、有症状和无症状的血栓栓塞事件以及药代动力学和药效学参数将作为次要结果进行评估。随机对照抗凝试验在儿童中具有挑战性。