Erythropoietin neuroprotection in neonatal cardiac surgery: A phase I/II safety and efficacy trial

Dean B. Andropoulos*, Kenneth Martin Brady, Ronald B. Easley, Heather A. Dickerson, Robert G. Voigt, Lara S. Shekerdemian, Marcie R. Meador, Carol A. Eisenman, Jill V. Hunter, Marie Turcich, Carlos Rivera, Emmett D. McKenzie, Jeffrey S. Heinle, Charles D. Fraser

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)124-131
Number of pages8
JournalJournal of Thoracic and Cardiovascular Surgery
Volume146
Issue number1
DOIs
StatePublished - Jul 2013

ASJC Scopus subject areas

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine

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