Darbe Administration in Newborns Undergoing Cooling for Encephalopathy
Status:
Completed
Trial end date:
2014-01-01
Target enrollment:
Participant gender:
Summary
Selective head cooling or whole body hypothermia has become the standard of care for neonatal
hypoxia-ischemia encephalopathy (HIE). Despite early intervention death or major
neurodevelopmental disability still occurs in nearly 50% of infants ≥ 36 weeks gestational
age (GA) treated with cooling. No additional therapies have proven to be efficacious in
further reducing brain injury and impairment for these high risk infants. Neuroprotective
strategies aimed at improving early childhood outcomes are still needed. An important area of
study includes therapies that may complement the neuroprotective effects of hypothermia and
promote neuronal regeneration, recovery and neurovascular remodeling. Among these therapies,
erythropoiesis stimulating agents (ESA) have been shown to provide neuroprotection, improving
short and long-term neurologic outcome in brain injury and HIE in neonatal and adult animal
models. Parallel with neuroprotective effects in experimental settings, recent small clinical
studies suggest improved outcomes after ESA administration in patients with severe traumatic
brain injury and HIE. ESA may work through several important mechanisms including reduced
inflammation, limited oxidative stress, decreased apoptosis and white matter injury, as well
as via pro-angiogenic and neurogenic properties.
Darbepoetin alfa (Darbe), a recombinant human erythropoietin (EPO)-derived molecule, has an
extended circulating half life and comparable biological activity to EPO, including
activation of the EPO receptor. The proposed study is a Phase I/II dose safety and
pharmacokinetic trial of early Darbe administered concurrent with hypothermia in human
newborn infants with moderate to severe birth asphyxia. The long-term objectives of the
proposed research are to reduce mortality and to decrease the risk of long-term disabilities
in infants with HIE who survive beyond the newborn period.