Clinical trial NCT03914690: Effect of Erythropoietin on Neurodevelopmental Outcomes in Very Preterm Infants With Intraventricular Hemorrhage
Official title: Effect of Erythropoietin on Neurodevelopmental Outcomes in Very Preterm Infants With Intraventricular Hemorrhage
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Premature Infants
Lead sponsor: Zhengzhou University
Sponsor class: OTHER
Collaborators: name: Zhengzhou Children's Hospital, China
name: Göteborg University
First posted: 2019-04-16
Enrollment: 316
Sex: ALL
Maximum age (years): 72
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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)

Primary outcomes:
measure: Mortality
timeFrame: At corrected age of 18 months
measure: Incidence of neurological disability
timeFrame: At corrected age of 18 months
Secondary outcomes:
measure: Incidence of cerebral palsy
timeFrame: At corrected age of 18 months
measure: Incidence of MDI<70
timeFrame: At corrected age of 18 months
measure: Incidence of blindness
timeFrame: At corrected age of 18 months
measure: Incidence of deafness
timeFrame: At corrected age of 18 months
measure: The effect of EPO treatment on blood mRNA expression
timeFrame: At 3 weeks after birth
Other outcomes:
Locations:
city: Zhengzhou
country: China
facility: Third Affiliated Hospital of Zhengzhou University
state: Henan
Study officials:
affiliation: Third Affiliated Hospital of Zhengzhou University
name: Changlian Zhu, PhD
role: STUDY_CHAIR
References:
citation: 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.