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

August 30, 2021 updated by: Huiqing Sun
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.

Study Overview

Status

Enrolling by invitation

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Enrollment (Anticipated)

440

Phase

  • Not Applicable

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 day to 3 days (CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: PREVENTION
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: DOUBLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: EPO group
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.
Drug: Recombinant human erythropoietin
rhEPO is administered 500IU/kg, intravenously within 72h after birth, and every other day up to 32 weeks of corrected age.
Other Names:
  • Epoietin Beta
PLACEBO_COMPARATOR: Normal saline
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.
Drug: Normal saline
Normal salin is administered the same volume with rhEPO intravenously within 72h after birth, and every other day up to 32 weeks of corrected age..

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mortality
Time Frame: 2 years
To compare the death rate of EPO and control groups at 2 years old
2 years
Incidence of neurological disability
Time Frame: 2 years
To assess the incidence of neurological disability of EPO and control groups at 2 years old
2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of MDI<70
Time Frame: 2 years
To compare the incidence of MDI<70 via Bayley Scales of Infant Development between the two groups at 2 years old
2 years
Incidence of cerebral palsy
Time Frame: 2 years
To compare the incidence of cerebral palsy between the two groups at 2 years old
2 years
Short-term complicatioins
Time Frame: 3 months
Retinopathy of prematurity, periventricular leukomalacia,Intraventricular hemorrhage, necrotising enterocolitis and sepsis
3 months
Incidence of blindness
Time Frame: 2 years
To compare the incidence of blindness via visual acuity between the two groups at 2 years old
2 years
Incidence of deafness
Time Frame: 2 years
To compare the incidence of blindness via auditory brainstem response measurements between the two groups at 2 years old
2 years
Early blood biomarkers for poor neurological outcomes
Time Frame: 4 weeks
To investigate early blood biomarkers via multi-omics to predict poor neurological outcomes
4 weeks
Brain imaging biomarkers for poor neurological outcomes
Time Frame: Up to 40 weeks of corrected age
To investigate Brain imaging biomarkers via MRI to predict poor neurological outcomes
Up to 40 weeks of corrected age

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Huiqing Sun

Collaborators

Göteborg University
Zhengzhou University

Investigators

  • Study Director: Ligong Hou, BD, Zhengzhou Children'S Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2016

Primary Completion (ANTICIPATED)

December 1, 2022

Study Completion (ANTICIPATED)

December 1, 2022

Study Registration Dates

First Submitted

March 16, 2016

First Submitted That Met QC Criteria

April 16, 2016

First Posted (ESTIMATE)

April 21, 2016

Study Record Updates

Last Update Posted (ACTUAL)

August 31, 2021

Last Update Submitted That Met QC Criteria

August 30, 2021

Last Verified

August 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CZS-EPO

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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