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

• ClinicalTrials.gov Identifier: NCT03914690
• Recruitment Status: Completed
• First Posted: April 16, 2019
• Last Update Posted: February 26, 2021
• Sponsor: Zhengzhou University
• Collaborators: Zhengzhou Children's Hospital, China; Göteborg University
• Information provided by (Responsible Party): Changlian Zhu, Third Affiliated Hospital of Zhengzhou University

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Premature Infants	Drug: Erythropoietin; Drug: Normal saline	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 316 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Effect of Erythropoietin on Neurodevelopmental Outcomes in Very Preterm Infants With Intraventricular Hemorrhage
• Actual Study Start Date: July 2014
• Actual Primary Completion Date: July 2019
• Actual Study Completion Date: July 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: 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.	Drug: Erythropoietin; EPO is administered 500IU/kg, intravenously after diagnosis of IVH within 72h after birth, and every other day for 2 weeks.; Other Name: Epoietin Beta
Placebo Comparator: 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.	Drug: 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.

Outcome Measures

Primary Outcome Measures :

1. Mortality [ Time Frame: At corrected age of 18 months ]
   To compare the death rate in EPO treatment and control groups at 18 months of corrected age.
2. Incidence of neurological disability [ Time Frame: 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 :

1. Incidence of cerebral palsy [ Time Frame: 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.
2. Incidence of MDI<70 [ Time Frame: 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.
3. Incidence of blindness [ Time Frame: 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.
4. Incidence of deafness [ Time Frame: 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.
5. The effect of EPO treatment on blood mRNA expression [ Time Frame: 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.

Eligibility Criteria

• Ages Eligible for Study: up to 72 Hours (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

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)

Contacts and Locations

Locations

China, Henan

Third Affiliated Hospital of Zhengzhou University

Zhengzhou, Henan, China, 450052

Sponsors and Collaborators

Zhengzhou University

Zhengzhou Children's Hospital, China

Göteborg University

Investigators

• Study Chair: Changlian Zhu, PhD; Third Affiliated Hospital of Zhengzhou University

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Song J, Wang Y, Xu F, Sun H, Zhang X, Xia L, Zhang S, Li K, Peng X, Li B, Zhang Y, Kang W, Wang X, Zhu C. Erythropoietin Improves Poor Outcomes in Preterm Infants with Intraventricular Hemorrhage. CNS Drugs. 2021 Jun;35(6):681-690. doi: 10.1007/s40263-021-00817-w. Epub 2021 May 6.

• Responsible Party: Changlian Zhu, Director, Clinical research center, Third Affiliated Hospital of Zhengzhou University
• ClinicalTrials.gov Identifier: NCT03914690
• Other Study ID Numbers: EPO2014
• First Posted: April 16, 2019
• Last Update Posted: February 26, 2021
• Last Verified: February 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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

Additional relevant MeSH terms:

Hemorrhage; Pathologic Processes; Epoetin Alfa; Hematinics