Erythropoietin neuroprotection in neonatal cardiac surgery: A phase I/II safety and efficacy trial
Erythropoietin neuroprotection in neonatal cardiac surgery: A phase I/II safety and efficacy trial
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新生儿心脏手术中的促红细胞生成素神经保护： I/II 期安全性和有效性试验
DOI：
10.1016/j.jtcvs.2012.09.046
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发表时间：
2013-07-01
影响因子：
6
通讯作者：
Fraser, Charles D., Jr.
中科院分区：
文献类型：
--
作者：
Andropoulos, Dean B.;Brady, Ken;Fraser, Charles D., Jr.
目的：接受复杂先天性心脏病手术的新生儿神经系统问题的发生率很高。促红细胞生成素具有抗凋亡、抗兴奋和抗炎特性，可预防动物模型中的神经元细胞死亡，并改善患有缺氧缺血性脑病的足月新生儿的神经发育结局。我们设计了一个前瞻性的I/II期试验促红细胞生成素神经保护新生儿心脏surgery，以评估安全性和指示effictiveness.Methods：新生儿接受手术的D-转位的大血管，发育不良的左心综合征，或主动脉弓重建随机3围手术期剂量的促红细胞生成素或安慰剂。在12个月大时进行神经发育测试，使用Bayley婴幼儿发育量表III。安全性特征，包括磁共振成像脑损伤，临床事件和死亡，组间无差异。每组各有3例患者死亡。42名患者（促红细胞生成素组22名，安慰剂组20名; 79%的幸存者）返回进行12个月的随访。在接受促红细胞生成素的组中，平均认知量表评分为101.1 +/- 13.6，语言量表评分为88.5 +/- 12.8，运动量表评分为89.9 +/- 12.3。在接受安慰剂的组中，认知量表评分为106.3 +/- 10.8（P = 0.19），语言评分为92.4 +/- 12.4（P = 0.33），运动量表评分为92.6 +/- 14.1（P = 0.51）。两组之间的神经发育结局没有差异;但是，这项初步研究没有能力明确解决这一结局。经验教训表明，优化的研究设计功能，一个更大的前瞻性试验，以明确解决的效用，促红细胞生成素的神经保护，在这一人群。
Objectives: Neonates undergoing complex congenital heart surgery have a significant incidence of neurologic problems. Erythropoietin has antiapoptotic, antiexcitatory, and anti-inflammatory properties to prevent neuronal cell death in animal models, and improves neurodevelopmental outcomes in full-term neonates with hypoxic ischemic encephalopathy. We designed a prospective phase I/II trial of erythropoietin neuroprotection in neonatal cardiac surgery to assess safety and indicate efficacy.Methods: Neonates undergoing surgery for D-transposition of the great vessels, hypoplastic left heart syndrome, or aortic arch reconstruction were randomized to 3 perioperative doses of erythropoietin or placebo. Neurodevelopmental testing using the Bayley Scales of Infant and Toddler Development III was performed at age 12 months.Results: Fifty-nine patients received the study drug. Safety profile, including magnetic resonance imaging brain injury, clinical events, and death, was not different between groups. Three patients in each group died. Forty-two patients (22 in the erythropoietin group and 20 in the placebo group; 79% of survivors) returned for 12-month follow-up. In the group receiving erythropoietin, mean Cognitive Scale scores were 101.1 +/- 13.6, Language Scale scores were 88.5 +/- 12.8, and Motor Scale scores were 89.9 +/- 12.3. In the group receiving placebo, Cognitive Scale scores were 106.3 +/- 10.8 (P.19), Language Scores were 92.4 +/- 12.4 (P = .33), and Motor Scale scores were 92.6 +/- 14.1 (P = .51).Conclusions: Safety profile for erythropoietin administration was not different than placebo. Neurodevelopmental outcomes were not different between groups; however, this pilot study was not powered to definitively address this outcome. Lessons learned suggest optimized study design features for a larger prospective trial to definitively address the utility of erythropoietin for neuroprotection in this population.