Recombinant Erythropoietin for Neuroprotection in Very Preterm Infants
Status:
Unknown status
Trial end date:
2011-07-01
Target enrollment:
Participant gender:
Summary
Periventricular leukomalacia (PVL) is one of the most common brain injuries that occur in
preterm infants. Inflammation, hypoxia-ischemia, free oxygen radical formation and
excitotoxicity are all known pathogenic mechanisms that mediate this injury. Erythropoietin
(EPO) has been shown to be protective against hypoxic-ischemic and inflammatory injuries.
During the past decade, recombinant human Epo (rhEpo) has been widely used in preterm infants
to prevent or treat the anemia of prematurity, in general, rhEpo has been considered to be
safe and well tolerated in preterm infants. EPO was considered not capable of passing through
blood-brain-barrier at low dose. Evidence from animal experiments reveals that rhEpo must be
given in high doses at the beginning or within a short (up to 6 hours), critical time period
after the onset of brain injury to achieve a significant neuroprotective effect. A recent
study using high-dose rhEpo (3000 U rhEpo/kg body weight at birth) for neuroprotection in
very preterm infants revealed that no signs of adverse effects of early high-dose rhEpo
treatment in very preterm infants were identified. Contrary to this, a recent study in PVL of
a rat model revealed that using a low dose rhEpo (50-100 U/kg) was effective in the treatment
of brain damage induced by hypoxia-ischemia and did not affect normal oligodendrocyte
maturity. On this basis, the researchers intent to investigate (1) whether low-dose rhEpo
(100 U/kg) or high-dose rhEpo (3,000 U/kg) given to very preterm infants (gestation age < 32
weeks) immediately after birth and subsequently during the first 2 days is safe and possesses
neuroprotective properties;(2) whether there are gender differences in response to the
hypoxia-ischemic insult and EPO treatment; (3)the pharmacokinetics of low dose and high dose
rhEPO. Very preterm infants with gestational age of < 32 weeks and admitted to the NICU are
eligible for enrollment.