Clinical Trial Details
— Status: Completed
Administrative data
NCT number |
NCT03071861 |
Other study ID # |
MEND 16-330 |
Secondary ID |
|
Status |
Completed |
Phase |
Phase 2
|
First received |
|
Last updated |
|
Start date |
December 1, 2017 |
Est. completion date |
September 1, 2022 |
Study information
Verified date |
December 2023 |
Source |
University of New Mexico |
Contact |
n/a |
Is FDA regulated |
No |
Health authority |
|
Study type |
Interventional
|
Clinical Trial 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.
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