Recombinant Human Erythropoietin Improve Neurodevelopmental Outcomes in Extremely Preterm Infants (EPO)

Huiqing Sun

Status: Unknown

Conditions: Developmental Disabilities

Treatments: Drug: Normal saline; Drug: Recombinant human erythropoietin

Study type: Interventional

Funder types: Other

Identifiers

NCT02745990

CZS-EPO

Details and patient eligibility

About

In the ELGAN (Extremely Low Gestational Age Newborn) study, abnormal brain structure and function were associated with intermittent or sustained systemic inflammation (ISSI). Since EPO has anti-inflammatory properties in the kidney and in muscle as well as growth/trophic properties. Based on its potential for neuroprotection, the prospective randomized and masked study was designed to determine whether rhEPO （500u/kg) was also effective in improving developmental outcomes for extremely low gestational age newborns.

Full description

Exogenous erythropoietin (EPO) is currently used to reduce or prevent the need for red blood cell transfusions in preterm infants. Just two decades ago, erythropoietin (EPO) receptors were first identified in the brain, and astrocytes were found to be capable of synthesizing EPO . Subsequently, it was found that cultured hippocampal and cerebral cortical neurons exposed to EPO were spared some of the glutamate-induced cell death seen in neurons not exposed to EPO. Thus began the concept that EPO protects the brain against adversity. Several follow-up studies of children who had participated in trials of recombinant EPO for the prevention or treatment of anemia, term newborn encephalopathy,or retinopathy of prematurity have also provided evidence of neuroprotective effects.

In the ELGAN (Extremely Low Gestational Age Newborn) study, abnormal brain structure and function were associated with intermittent or sustained systemic inflammation (ISSI) . Since EPO has anti-inflammatory properties in the kidney and in muscle as well as growth/trophic properties, we reasoned that elevated circulating levels might convey information about reduced risk of brain damage in ELGANs.

Although major neurodevelopmental disabilities such as cerebral palsy (CP), mental disabilities, and learning and attention deficits during school age figure prominently in the outcomes of ELBW infants, successful neuroprotective interventions have yet to be developed. Investagators designed a prospective, randomized, masked study to evaluate rhEPO during initial hospitalization and follow up, and hypothesized that rhEPO recipients would receive fewer transfusions during initial hospitalization in extremely preterm infants. Based on its potential for neuroprotection, our study was designed to determine whether rhEPO (500 u/kg) was also effective in improving developmental outcomes for extremely low gestational age newborns.

The neurodevelopmental outcomes of rhEPO in treating extremely preterm infants are not clear. Investigators propose an early-childhood neurodevelopmental follow-up study to compare long-term effects of the rhEPO as measured by, Bayley Scales of Infant Development III. We plan to follow extremely low gestational age children around 24 months' corrected age (CA) who are enrolled in this study.

Enrollment: 440 estimated patients

Sex: All

Ages: 1 to 3 days old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Preterm infants admitted to NICU wuth gestational age less than 28 weeks
• Age less than 3 days;
• parental informed consent.

Exclusion criteria

• Major life-threatening anomalies (brain, cardiac, chromosomal anomalies)
• Hematologic crises such as DIC, or hemolysis due to blood group incompatibilities
• Polycythemia (hematocrit > 65);
• Hypertension
• Seizures
• Congenital infection

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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440 participants in 2 patient groups, including a placebo group

EPO group

Experimental group

Description:

In EPO group, The recombinant human erythropoietin (rhEPO) will be given by 500 U/kg/dose intravenously within 72h after birth, and every other day up to 32 weeks of corrected age.

Treatment:

Drug: Recombinant human erythropoietin

Normal saline

Placebo Comparator group

Description:

Normal saline is administered the same volume with EPO, intravenously within 72h after birth, and every other day up to 32 weeks of corrected age.

Treatment:

Drug: Normal saline