Erythropoietin Protects Very Preterm Infants Against Necrotizing Enterocolitis

This study evaluates the effect of repeated low-dose erythropoietin (EPO) treatment on necrotizing enterocolitis (NEC) in very preterm infants. Half of participants will receive EPO, while the other half will receive a placebo.

Study Overview

• Status: Completed
• Conditions: Premature Infant
• Intervention / Treatment: Drug: EPO; Drug: Normal saline

Detailed Description

NEC is one of the most severe complications in preterm neonates and is associated with high morbility and mortality. Studies have reported that EPO treatment decreases the incidence and severity of experimental NEC in animal models. Evidence from previous clinical studies about the effect of EPO treatment against NEC have all been hampered by small numbers of patients. The study is to investigate whether repeated low-dose EPO protects against NEC. Preterm infants with gestational age ≤32 weeks who are admitted to neonatal intensive care units within 72 hours after birth are randomized to EPO (500IU/kg, intravenously every other day for 2 weeks) or control group (the same volume of saline). Primary outcome is the incidence of NEC at 36 weeks of corrected age. Secondary outcome is growth and neurodevelopment at 18 months of corrected age in infants with NEC.

• Study Type: Interventional
• Enrollment (Actual): 1285
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Henan
    • Zhengzhou, Henan, China, 450052
      • Third Affiliated Hospital of Zhengzhou University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 3 days (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Preterm infants with gestation age ≤ 32weeks
• Within 72 hours after birth
• Written informed consent obtained from parents

Exclusion Criteria:

• Genetic or metabolic diseases
• Congenital abnormalities
• Polycythemia
• Intracranial hemorrhage grade III/IV
• Unstable vital signs (such as respiration and circulation failure)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Erythropoietin; Infants in the EPO group are given EPO 500IU/kg dissolved in 2 ml saline intravenously every other day for 2 weeks starting within 72 hours after birth.	Drug: EPO; Infants in EPO group are administered 500IU/kg intravenously within 72 hours after birth every other day for 2 weeks.; Other Names: Epoetin Beta
Placebo Comparator: Normal saline; Infants in the control group are given normal saline intravenously with the same volume as EPO every other day for 2 weeks.	Drug: Normal saline; Infants in control group are administered normal saline with the same volume and period as EPO.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of NEC	To compare the incidence of NEC between EPO group and control group at 36 weeks of corrected age	At 36 weeks of corrected age

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of low height in patients with NEC	To compare the incidence of low height in patients with NEC between EPO and control groups via the Standardized Growth Curve for Chinese Children at 18 months of corrected age.	At corrected age of 18 months
Incidence of low weight in patients with NEC	To compare the incidence of low weight in patients with NEC between EPO and control group via the Standardized Growth Curve for Chinese Children at 18 months of corrected age.	At corrected age of 18 months
Incidence of low head circumference in patients with NEC	To compare the incidence of low head circumference in patients with NEC between EPO and control group via the Standardized Growth Curve for Chinese Children at 18 months of corrected age.	At corrected age of 18 months
Incidence of MDI<70 in patients with NEC	To compare the incidence of MDI<70 in patients with NEC between EPO and control group via Bayley Scales of Infant Development (second edition) at 18 months of corrected age.	At corrected age of 18 months
Incidence of cerebral palsy in patients with NEC	To compare the incidence of cerebral palsy in patients with NEC between EPO and control group at 18 months of corrected age.	At corrected age of 18 months
Incidence of blindness in patients with NEC	To compare the incidence of blindness in patients with NEC between EPO and control group via visual acuity at 18 months of corrected age.	At corrected age of 18 months
Incidence of deafness in patients with NEC	To compare the incidence of deafness in patients with NEC between EPO and control group via auditory brainstem response measurement at 18 months of corrected age.	At corrected age of 18 months
The effect of EPO treatment on blood messenger RNA (mRNA) expression	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.	At 3 weeks after birth

Collaborators and Investigators

• Sponsor: Zhengzhou University
• Collaborators: Göteborg University; The First Affiliated Hospital of Zhengzhou University; Zhengzhou Children's Hospital, China; Women and Children Health Care Center of Luoyang, China
• Investigators: Study Chair: Changlian Zhu, PhD, Third Affiliated Hospital of Zhengzhou University

Publications and helpful links

General Publications

• Sun H, Song J, Kang W, Wang Y, Sun X, Zhou C, Xiong H, Xu F, Li M, Zhang X, Yu Z, Peng X, Li B, Xu Y, Xing S, Wang X, Zhu C. Effect of early prophylactic low-dose recombinant human erythropoietin on retinopathy of prematurity in very preterm infants. J Transl Med. 2020 Oct 19;18(1):397. doi: 10.1186/s12967-020-02562-y.
• Wang Y, Song J, Sun H, Xu F, Li K, Nie C, Zhang X, Peng X, Xia L, Shen Z, Yuan X, Zhang S, Ding X, Zhang Y, Kang W, Qian L, Zhou W, Wang X, Cheng X, Zhu C. Erythropoietin prevents necrotizing enterocolitis in very preterm infants: a randomized controlled trial. J Transl Med. 2020 Aug 8;18(1):308. doi: 10.1186/s12967-020-02459-w.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2014
• Primary Completion (Actual): April 1, 2019
• Study Completion (Actual): April 1, 2019

Study Registration Dates

• First Submitted: April 11, 2019
• First Submitted That Met QC Criteria: April 15, 2019
• First Posted (Actual): April 18, 2019

Study Record Updates

• Last Update Posted (Actual): April 19, 2019
• Last Update Submitted That Met QC Criteria: April 17, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: Erythropoietin; Neurodevelopment; Necrotizing enterocolitis; Preterm infant
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Enterocolitis; Enterocolitis, Necrotizing
• Other Study ID Numbers: HN-2014002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: De-identified individual participant data for all primary and secondary outcome measures will be made available.
• IPD Sharing Time Frame: Data will be available within 6 months of study completion
• IPD Sharing Access Criteria: Data access requests will be assessed by sponsor. Requestors will be required to sign a Data Access Agreement.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No