Randomized, placebo-controlled, double-blind trial of T3 in infant heart surgery

描述（由申请人提供）： 病态甲状腺功能正常综合征在婴幼儿和儿童接受体外循环心脏手术后很常见。最近的数据表明，心脏手术后补充三碘甲状腺原氨酸（T3）可能会改善术后结局。我们提出了一个随机，双盲，安慰剂对照试验，以评估T3补充对新生儿接受诺伍德程序的术后过程和后来的神经发育结果的影响。T3将在旁路停止后给药72小时。两个治疗组的儿童将接受常规治疗。根据文献和我们自己的初步研究，我们预计T3将有很少的不良反应。我们的第一个目的是检验以下假设：与安慰剂相比，T3补充剂与更好的术后早期血流动力学状态和更快的术后恢复相关。我们的主要结局指标将是综合临床结局评分，数值范围为0-7，基于首次达到负液体平衡的时间;胸骨闭合的时间;首次拔管的时间;以及死亡或使用ECMO的发生率。次要结局将包括临床结局评分的各个组成部分，以及术后最初5天内的正性肌力药物需求、心肌性能指数、旁路术终止后的血清乳酸盐蓄积;术后在ICU和医院的停留时间;以及严重不良事件的发生率。我们的第二个目的是检验与安慰剂相比，T3补充剂与上级发育结果相关的假设。我们的主要结果变量将是一岁时贝利婴儿发展量表的心理发展指数（PDI）评分。次要结局将包括贝利量表的精神发育指数（MDI）、麦克阿瑟沟通发展指数和功能状态II修订版问卷。本研究的结构将使我们能够探索术后T3水平与术前、术中和术后早期管理策略的关系，包括使用甲状腺功能调节剂，如局部碘、碘化造影剂和多巴胺。该试验将从入组开始到完成随访持续三年。如果T3治疗被发现对诺伍德人群有利，它可能会使许多其他需要在婴儿早期手术的先天性心脏病儿童受益。在接受诺伍德手术的婴儿中了解到的有关甲状腺激素状态与其他内科和外科治疗相互关系的信息，对这些特别复杂和高风险患者的整体管理做出了重要贡献。本研究利用了在儿科心脏网络的研究方案中招募和管理接受诺伍德手术的婴儿所积累的专业知识和动力。(End抽象）。

DESCRIPTION (provided by applicant): Sick euthyroid syndrome is common among infants and children following cardiac surgery using cardiopulmonary bypass. Recent data suggest that triiodothyronine (T3) supplementation after cardiac surgery may improve postoperative outcomes. We propose a randomized, double-blind, placebo controlled trial to evaluate the effect of T3 supplementation on the postoperative course and later neurodevelopmental outcome in neonates undergoing the Norwood procedure. T3 will be administered for 72 hours after cessation of bypass. Children in both treatment groups will receive conventional therapy. Based upon the literature and our own pilot study, we anticipate that T3 will have few adverse effects. Our first aim is to test the hypothesis that T3 supplementation, compared to placebo, will be associated with better early postoperative hemodynamic status and faster postoperative recovery. Our primary outcome measure will be a composite clinical outcome score, with values from 0-7, based upon the time until negative fluid balance is first achieved; time until sternal closure; time until first extubation; and the occurrence of death or use of ECMO. Secondary outcomes will include individual components of the clinical outcome score, as well as inotrope requirement over the initial 5 postoperative days, myocardial performance index, serum lactate accumulation following the termination of bypass; length of postoperative stay in the ICU and hospital; and incidence of serious adverse events. Our second aim is to test the hypothesis that T3 supplementation, compared to placebo, will be associated with superior developmental outcome. Our primary outcome variable will be score on the Psychodevelopment Index (PDI) of the Bayley Scales of Infant Development at age one year. Secondary outcomes will include the Mental Development Index (MDI) of the Bayley Scales, the MacArthur Communicative Developmental Index, and the Functional Status Il-Revised questionnaire. The structure of the study will allow us to explore the relationship of postoperative T3 levels to preoperative, intraoperative and early postoperative management strategies, including use of modifiers of thyroid function such as topical iodine, iodinated contrast, and dopamine. The trial will span three years from onset of enrollment until completion of follow-up. If T3 therapy is found to be advantageous to the Norwood population, it may benefit many other children with congenital heart disease who require surgery in early infancy. The information learned about the interrelationships of thyroid hormone status and other medical and surgical therapies in infants undergoing the Norwood procedure makes an important contribution to the overall management of these particularly complex and high-risk patients. This study takes advantage of the expertise and momentum accumulated in enrolling and managing infants undergoing the Norwood procedure in research protocols within the Pediatric Heart Network. (End of Abstract).