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

NCT ID: NCT03914690

Last Updated: 2021-02-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 316 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-07-31
• Study Completion Date: 2019-07-31

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.

Conditions

Premature Infants

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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.

Group Type: EXPERIMENTAL

Erythropoietin

Intervention Type: DRUG

EPO is administered 500IU/kg, intravenously after diagnosis of IVH within 72h after birth, and every other day for 2 weeks.

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.

Group Type: PLACEBO_COMPARATOR

Normal saline

Intervention Type: DRUG

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.

Interventions

Erythropoietin

EPO is administered 500IU/kg, intravenously after diagnosis of IVH within 72h after birth, and every other day for 2 weeks.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

Epoietin Beta

Eligibility 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)

• Maximum Eligible Age: 72 Hours
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Zhengzhou Children's Hospital, China

OTHER

Sponsor Role: collaborator

Göteborg University

OTHER

Sponsor Role: collaborator

Zhengzhou University

OTHER

Sponsor Role: lead

Responsible Party

Changlian Zhu

Director, Clinical research center

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Changlian Zhu, PhD

Role: STUDY_CHAIR

Third Affiliated Hospital of Zhengzhou University

Locations

Third Affiliated Hospital of Zhengzhou University

Zhengzhou, Henan, China

Countries

China

References

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.

Reference Type: DERIVED

PMID: 33959935 (View on PubMed)

Other Identifiers

EPO2014

Identifier Type: -

Identifier Source: org_study_id