Effect of Erythropoietin in Premature Infants on White Matter Lesions and Neurodevelopmental Outcome

September 28, 2017 updated by: First Affiliated Hospital Xi'an Jiaotong University

Effect of Early Application of Recombinant Human Erythropoietin in Premature Infants on White Matter Lesions and Neurodevelopmental Outcome

Preterm and very preterm infants are at risk of developing encephalopathy of prematurity and long-term neurodevelopmental delay. Magnetic resonance imaging (MRI) allows the characterization of specific features of encephalopathy of prematurity, including structural changes of brain white matter and gray matter. This study wants to investigate important evidence that early repeated high-dose rhEPO(5250 IU/kg) treatment improves long-term neurological outcomes in very preterm infants and without obvious adverse effects.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

HYPOTHESIS Early administration of human erythropoietin (EPO) in preterm infants reduces perinatal injury to the brain and improves neurodevelopmental outcome at 24 months corrected age.

PRIMARY OBJECTIVE To determine whether cerebral outcome is improved if infants born between 28 0/7 and 34 6/7 gestational weeks at birth receive erythropoietin in high dose in the first two weeks after birth.

Biomarkers of encephalopathy of prematurity assessed on magnetic resonance imaging (MRI) at term equivalent age.

RATIONALE Erythropoietin (EPO) was first recognized for its hematopoietic properties; recombinant human EPO (rhEPO) has been used to treat a number of anemic states, including early and late anemia of prematurity, and it has been found to be safe and to reduce the need for blood transfusions. EPO produced in the central nervous system7 is upregulated after insult and plays a role in neuroprotection. Experimental studies have reported that rhEPO possesses neuroprotective properties in different neonatal brain injury animal models, and clinical studies have shown that rhEPO treatment reduces brain injury and the incidence of neurological disabilities in infants.8,14-17 In addition, improved neurodevelopmental outcomes have been observed in preterm infants with anemia after rhEPO treatment. The neuroprotective effect of rhEPO was suggested to be through acting against apoptosis, inflammation, and neurotoxicity and by acting as an antioxidant in protecting white matter from injury and in promoting neural regeneration, injury repair, and normal development.

STUDY DESIGN Randomized, double-masked, placebo-controlled multicenter clinical trial. Research plan 400 infants will be randomized during the first three hours of life to receive EPO (5250 U/kg body weight) or placebo intravenously, the first dose(750U/kg) will be injected within 24h after birth, subsequent injection will be given each other day for 2 weeks. Standardized evaluation including cerebral sonography at day 1, 7 and 28 will determine the presence or absence of complications. Cerebral volume and white matter volume will be assessed at 40 postmenstrual weeks with MRI (only if available).

Experienced examiners will assess developmental function at 6 and 12 months corrected age using the reliable and validly revised Bayley Scales III of Infant Development and determine the presence or absence of impairment of motor function (cerebral palsy) and neurosensory function (blindness or deafness).

Primary outcome was cognitive development assessed with the Mental Development Index (MDI; norm, 100 [SD, 15]; higher values indicate better function) of the Bayley Scales of Infant Development, second edition (BSID-II) at 1 years corrected age.

Second outcome assess the effect of early administration of rh Epo on white matter development in preterm infants using Tract-based spatial statistics (TBSS ). White matter disease of the preterm infant, was semiquantitatively assessed from MRI at term-equivalent age based on an established scoring method.

Study Type

Interventional

Enrollment (Anticipated)

400

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Shaanxi
      • Xi'an, Shaanxi, China, 710061
        • Recruiting
        • First Affiliated Hospital of Xian JiaotongUniversity
        • Contact:

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

No older than 3 days (CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • premature infants who admitted to the neonatal intensive care unit(NICU) Within 72 hours after birth, gestational ages younger than 32 weeks, birth weight less than 1500 gram, informed consent was obtained from the infants' parents or guardians

Exclusion Criteria:

  • born with anemia, polycythemia, hemolysis and other hematological diseases
  • hypertension,
  • convulsions,
  • a genetically defined syndrome
  • a severe congenital malformation adversely affecting life expectancy or neurodevelopment
  • severe intraventricular hemorrhage
  • thrombosis disease
  • other fatal diseases or which can seriously affect the prognosis

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: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: DOUBLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Erythropoietin
Erythropoietin is administered 750U/kg intravenously every other day for 2 weeks (a cumulative dose of 5,250U/kg over the course of 7 separate intravenous injections regardless of gestational age), starting with the first dose within 72 hours after birth. A single dose consisted of 750U EPO per kg of birth weight dissolved in 3mL/kg normal saline was administered intravenously during a period of 5 minutes.
Drug: Normal saline
placebo (Normal saline 3 ml/kg birth weight) was injected within 72h after birth, subsequent injection was given every other day for 2 weeks.
Other Names:
  • NaCl 0.9%
PLACEBO_COMPARATOR: Normal saline
Normal saline is administered 3ml/kg intravenously every other day for 2 weeks, starting with the first dose within 72 hours after birth. Similarly, the placebo dose consisted of 3mL of normal saline per kilogram birth weight was administered intravenously during a period of 5 minutes.
Drug: Erythropoietin
rhEPO 750U/kg was injected within 72h after birth, subsequent injection was given every other day for 2 weeks (a cumulative dose of 5,250U/kg over the course of 7 separate intravenous injections.
Other Names:
  • Epoetin Beta

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Neurodevelopmental outcome
Time Frame: corrected age of 18 months
To evaluate neurodevelopmental function via Bayley Scales of Infant Development, second edition (BSID-II) at 18 months corrected age and gain incidence of MDI<70(Severe) or MDI<85(Moderate).
corrected age of 18 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
TBSS（Tract-based spatial statistics）
Time Frame: corrected age of 40 weeks
White matter disease of the preterm infant, was semiquantitatively assessed from MRI at term-equivalent age based on an established scoring method.
corrected age of 40 weeks

Collaborators and Investigators

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

Sponsor

First Affiliated Hospital Xi'an Jiaotong University

Collaborators

Xijing Hospital
Shaanxi Provincial People's Hospital
Second Affiliated Hospital of Xi'an Jiaotong University
Tang-Du Hospital
Xian Children's Hospital
Northwest Women's and Children's Hospital, Xi'an, Shaanxi
Xi'an No.4 Hospital

Investigators

  • Principal Investigator: Xihui Zhou, Doctor, First Affiliated Hospital of Xian JiaotongUniversity

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 (ACTUAL)

April 10, 2017

Primary Completion (ANTICIPATED)

December 1, 2018

Study Completion (ANTICIPATED)

June 1, 2019

Study Registration Dates

First Submitted

March 15, 2017

First Submitted That Met QC Criteria

April 6, 2017

First Posted (ACTUAL)

April 12, 2017

Study Record Updates

Last Update Posted (ACTUAL)

October 2, 2017

Last Update Submitted That Met QC Criteria

September 28, 2017

Last Verified

September 1, 2017

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • XJTU1AF-CRF-2016-023

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

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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