Clinical Trial: Recombinant Erythropoietin for Neuroprotection in Very Preterm Infants

Study Status: Completed
Recruit Status: Unknown status
Study Type: Interventional

Official Title: Early Treatment With Recombinant Erythropoietin for Neuroprotection in Very Preterm Infants: Comparison of High and Low Dose

Brief 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.

Detailed 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. Although several treatment strategies have been devised, few therapies effectively mitigate the harmful effects of hypoxia-ischemia in preterm newborns and the ensuing neurodevelopment sequelae. Erythropoietin (EPO) has been shown to be protective against hypoxic-ischemic and inflammatory injuries in neuronal cell culture, animal models of brain injury, and clinical trials of adult humans. 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. Clinical studies suggest that gender influences the response to brain injury. Ment and coworkers have reported that the cyclooxygenase inhibitor indomethacin ameliorated intraventricular hemorrhage and improved cognition in very low birth weight boys, but not girls. On this basis, the researchers intent to investigate (i) whether low-dose
Sponsor: China Medical University Hospital

Current Primary Outcome: The primary short-term outcome measures are brain injury (intraventricular hemorrhage (IVH) and periventricular leukomalacia (PVL)) and ROP. [ Time Frame: 2 months ]

Original Primary Outcome: Same as current

Current Secondary Outcome: The secondary outcomes are sepsis, necrotizing enterocolitis (NEC), persistent ductus arteriosus (PDA), apnea of prematurity, and chronic lung disease. [ Time Frame: 2 months ]

Original Secondary Outcome: Same as current

Information By: China Medical University Hospital

Dates:
Date Received: May 28, 2009
Date Started: August 2009
Date Completion: July 2011
Last Updated: May 28, 2009
Last Verified: May 2009