Mild Encephalopathy in the Newborn Treated With Darbepoetin
Condition: Neonatal Encephalopathy; Hypoxic-Ischemic Encephalopathy Mild
MeSH terms: Brain Diseases; Brain Ischemia; Hypoxia-Ischemia, Brain
Study type: Interventional
Phase: Phase 2

Summary: 
      This is a Phase II multicenter placebo-controlled randomized, feasibility/safety trial.
      Infants >34 week gestational age with perinatal acidemia and mild neonatal encephalopathy on
      the modified Sarnat neurologic examination at less than six hours of age. Participants will
      be randomized to receive either one dose of Darbepoetin, or placebo within 24 hours of birth.
      Neurodevelopmental testing (Bayley (III or IV) and Gross Motor Function Assessment) will be
      performed at 24 months of age. Pharmacokinetics will be assessed on those infants that
      received Darbe.
    

Detailed description: 
      Therapeutic hypothermia (TH) is the standard of care for newborns diagnosed with moderate to
      severe neonatal encephalopathy (NE) presumably due to hypoxic ischemia. In order to be
      eligible for TH an infant must have perinatal acidemia and evidence of moderate or severe
      encephalopathy on a standardized neurologic examination (Sarnat). However, the majority of
      newborns with perinatal acidemia do not have a neurologic examination abnormal enough to be
      classified as moderate or severe NE. In a retrospective review, DuPont et al. found that as
      many as 20% of newborns with perinatal academia and mild NE have abnormal short-term outcomes
      such as seizures, death from progressive asphyxia insult, brain MRI findings consistent with
      NE, abnormal neurologic examination at discharge, gastrostomy tube feeding, or feeding
      difficulties. Preliminary data from a prospective trial investigating mild NE (PRIME study,
      NCT01747863) found that 39% had either abnormal electroencephalography at < 9h of age, an
      abnormal brain MRI finding, or abnormal neurological exam at discharge. Murray et al.
      recently reported on 5-year outcomes of infants with mild encephalopathy and showed that 25%
      had neurodevelopmental disability. These data suggest that mild NE likely carries a higher
      risk of impaired neurological outcome then reported previously. Thus it would appear that
      neuroprotective strategies would be beneficial in this group of infants. Preliminary data
      suggest that erythropoiesis stimulating agents (ESA) provide neuroprotection, and improve
      short and long-term neurologic outcome in neonatal brain injury. ESA may work through several
      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 established
      safety and pharmacokinetics in newborns. Because Darbe has an extended circulating half-life
      with comparable biological activity to EPO, it has the advantage of requiring less frequent
      administration
    

Intervention name(s): Darbepoetin Alfa; Normal Saline
Intervention type(s): Drug; Drug
Intervention description(s): Single dose of 10 mcg/kg Darbepoetin Alpha given IV at less than 24 hours of age; Single dose of normal saline, IV, given at less than 24 hours of age
Other intervention name(s): Darbe; Darbepoetin
Intervention MeSH terms: Darbepoetin alfa
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: darbepoetin; Brain Diseases