This planning grant will be used to develop a detailed research plan in order to carry out a multicenter randomized controlled trial of high dose recombinant erythropoietin (rEpo) as an early intervention to improve long-term neurological outcomes in extremely low birth weight infants (ELBW), those born <29 weeks of gestation, and d1000g. Long-term survival of ELBW infants has improved over the last two decades. However, since a relatively constant proportion of survivors are impaired, this has resulted in a larger number of impaired survivors. Major morbidities include cerebral palsy, deafness, blindness, and mental retardation, and one or more of these problems is present in up to 48% of survivors. There are currently no neuroprotective treatments available for ELBW infants. rEpo has neuroprotective effects in models of brain injury, and is safe when used clinically to promote erythropoiesis. ELBW infants were chosen for this study because of their high risk of poor neurodevelopmental outcome, and the high likelihood that early high dose rEpo will have a beneficial effect. The new frontier of neonatology must include development of new treatment strategies that improve the neurological outcomes of these vulnerable infants. Funding of this proposal will allow for the planning of a novel approach to neuroprotection. Success of such a clinical trial will have a major impact on the health and well being of our children, their families, and will also have important economic benefits, since preterm infants utilize a disproportionate share of our health care and education dollars. We have put together a group of experts from eleven centers across the United States to plan and execute this study. All investigators have experience and interest in neurodevelopment and with clinical trials. The inclusion of these centers will insure that enough patients are enrolled, and that there is diversity among subjects so the results can be generalized. In order to launch a successful multicenter randomized controlled clinical trial, many details must be in place before the trial begins. The expected product of this grant is a detailed clinical trial research plan including a complete manual of operations and procedures. Grant funding for the phase III trial will also be sought during the last 6 months of this planning grant.
A detailed research plan (including a complete manual of operations and procedures) will be formulated in order to carry out a multicenter randomized controlled trial of high dose recombinant erythropoietin (rEpo) as an early intervention to improve long-term neurological outcomes in extremely low birth weight infants (ELBW), those born d1000g. ELBW infants were chosen for this study because of their high risk of poor neurodevelopmental outcome (up to 48%), and the high likelihood that early high dose rEpo will have a beneficial effect. Success of such a clinical trial will have a major impact on the health and well being of our children, their families, and will also have important economic benefits, since preterm infants utilize a disproportionate share of our health care and education dollars.
| Juul, Sandra E (2013) Hypothermia plus erythropoietin for neonatal neuroprotection? Commentary on Fan et al. and Fang et al. Pediatr Res 73:10-1 |
| Mann, Paul C; Woodrum, David E; Wilfond, Benjamin S (2013) Fuzzy images: Ethical implications of using routine neuroimaging in premature neonates to predict neurologic outcomes. J Pediatr 163:587-92 |
| McPherson, Ronald J; Juul, Sandra E (2010) Erythropoietin for infants with hypoxic-ischemic encephalopathy. Curr Opin Pediatr 22:139-45 |
