Recombinant Erythropoietin for Neuroprotection in Very Preterm Infants

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.

Conditions

• Infant, Premature
• Leukomalacia, Periventricular
• Intraventricular Hemorrhage
• Retinopathy of Prematurity

Interventions

DRUG

recombinant human erythropoietin (rhEpo)

rhEpo is administered 3000 U/kg, iv at 3 to 6 hours after birth, and at 24 hours interval for another 2 doses.

DRUG

recombinant human erythropoietin (rhEpo)

rhEpo is administered 100 U/kg, iv at 3 to 6 hours after birth, and at 24 hours interval for another 2 doses.

DRUG

Normal saline

normal saline is administered 0.5/kg, iv at 3 to 6 hours after birth, and at 24 hours interval for another 2 doses.

Sponsors & Collaborators

• China Medical University Hospital

  lead OTHER

Principal Investigators

• Bai-Horng Su, MD, PhD · China Medical University Hospital

Study Design

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

2 Hours

Max Age

6 Hours

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2009-08-31

Primary Completion

2011-07-31

Completion

2011-07-31

Countries

• Taiwan

Study Locations