Effect of Erythropoietin on Neurodevelopmental Outcomes in Very Preterm Infants With Intraventricular Hemorrhage

Phase 2

Completed

• Conditions: Premature Infants
• Interventions: Drug: Normal saline; Drug: Erythropoietin

• Registration Number: NCT03914690
• Lead Sponsor: Zhengzhou University

Brief Summary

Erythropoietin (EPO) has been shown to be neurotrophic and neuroprotective in several animal models and some clinical studies. Our hypothesis is that EPO could improve long-term neurological outcomes in very preterm infants with intraventricular hemorrhage (IVH). The aim of this study is to evaluate the long-term neuroprotective effect of repeated low-dose EPO (500 U/kg) in very preterm infants with IVH.

Detailed Description

IVH is one of the most common complications in preterm infants. Nearly 60% of preterm infants with grade III-IV IVH develop severe neurodevelopmental outcomes. There are currently no effective treatments to prevent preterm infants with IVH from developing ventricular dilation or serious neurological disabilities. Recent studies have shown that EPO could improve neurodevelopmental outcomes in preterm infants with grade III-IV IVH. However, the dose and course of EPO in preterm infants is still uncertain. The purpose of the study was whether repeated low-dose EPO (500 U/kg, every other day, for 2 weeks) given to very preterm right after the diagnosis of IVH could improve long-term neurological outcomes. Very preterm infants with gestational age of ≤ 32 weeks who are diagnosed with IVH within 72 hours after birth in NICU are eligible for enrolment. After informed consent is obtained, infants will be randomly assigned to EPO group or vehicle group. The primary outcome is whether EPO improves mortality and neurological disabilities in very preterm infants with IVH at 18 months of corrected age, and the secondary outcome was whether EPO decrease the incidence of cerebral palsy, MDI\<70, blindness, and deafness.

Study Timeline

• Study Start: 2014-07
• Study First Submitted: 2019-04-11
• Study First Submitted QC: 2019-04-11
• Study First Posted: 2019-04-16
• Primary Completion: 2019-07
• Study Completion: 2019-07
• Status Verified: 2021-02
• Last Update Submitted: 2021-02-25
• Last Update Posted: 2021-02-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 316

Inclusion Criteria

• Preterm infants admitted to NICU ≤ 32 weeks gestation at birth
• Birth weight less than 1500 g
• Less than 72 hours of life at time of enrolment
• Diagnosed as IVH by head ultrasound
• Written informed consent of parent or guardian

Read More

Exclusion Criteria

• Genetic metabolic diseases
• Congenital abnormalities
• Polycythaemia (Hct > 65%) within first 24 hours of life
• Thrombocytopenia (platelets < 50K cells/microL) within first 24 hours of life
• Unstable vital signs (such as respiration and circulation failure)

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Normal saline	Normal saline	Normal saline is administered the same volume with EPO, intravenously after diagnosis of IVH within 72h after birth, and every other day for 2 weeks.
Erythropoietin	Erythropoietin	EPO is administered 500IU/kg, intravenously after diagnosis of IVH within 72h after birth, and every other day for 2 weeks. Recombinant human erythropoietin was configured by the hospital pharmacy intravenous Centre Configuration, melted configured with saline to 1ml/kg solution.

Primary Outcome Measures

Name	Time	Method
Mortality	At corrected age of 18 months	To compare the death rate in EPO treatment and control groups at 18 months of corrected age.
Incidence of neurological disability	At corrected age of 18 months	To evaluate neurodevelopmental function via Bayley Infant Development scale (2nd Edition), visual acuity and auditory brainstem response measurements at 18 months of corrected age.

Secondary Outcome Measures

Name	Time	Method
Incidence of MDI<70	At corrected age of 18 months	To compare the incidence of MDI\<70 via Bayley Infant Development scale (2nd Edition) in EPO treatment and control groups at 18 months of corrected age.
Incidence of cerebral palsy	At corrected age of 18 months	To compare the incidence of cerebral palsy in EPO treatment and control groups at 18 months of corrected age.
Incidence of blindness	At corrected age of 18 months	To compare the incidence of blindness via visual acuity and sight radius examinations in EPO treatment and control groups at 18 months of corrected age.
Incidence of deafness	At corrected age of 18 months	To compare the incidence of deafness via auditory brainstem response measurements in EPO treatment and control groups at 18 months of corrected age.
The effect of EPO treatment on blood mRNA expression	At 3 weeks after birth	To investigate different mRNA expression between EPO and control group, peripheral venous blood of preterm infants after EPO treatment will be collected in both EPO group and control group, and the transcriptome of the premature infant blood will be assayed by RNA sequencing.

Trial Locations

Locations (1)

Third Affiliated Hospital of Zhengzhou University; 🇨🇳 Zhengzhou, Henan, China