Erythropoietin Protects Very Preterm Infants Against Necrotizing Enterocolitis

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Erythropoietin Protects Very Preterm Infants Against Necrotizing Enterocolitis

Conditions
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Premature Infant

Intervention / Treatment
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* Drug: EPO
* Drug: Normal saline


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Maximum Age: 72 Hours

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Erythropoietin<br>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<br>* Infants in EPO group are administered 500IU/kg intravenously within 72 hours after birth every other day for 2 weeks.<br>* Other names: Epoetin Beta;|
| Placebo Comparator: Normal saline<br>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<br>* Infants in control group are administered normal saline with the same volume and period as EPO.<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Preterm infant, Necrotizing enterocolitis, Erythropoietin, Neurodevelopment