Erythropoietin Protects Very Preterm Infants Against Necrotizing Enterocolitis

• Sponsor: Zhengzhou University (Other)
• Overall Status: Completed
• CT.gov ID: NCT03919500
• Collaborator: Zhengzhou Children's Hospital, China (Other), The First Affiliated Hospital of Zhengzhou University (Other), Women and Children Health Care Center of Luoyang, China (Other), Göteborg University (Other)
• Enrollment: 1,285
• Location: 1
• Arms: 2
• Actual Duration (Months): 62.9
• Patients Per Site Per Month: 20.4

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Premature Infant	Drug: EPO; Drug: Normal saline	Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 1285 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Erythropoietin Protects Very Preterm Infants Against Necrotizing Enterocolitis
• Actual Study Start Date: Jan 1, 2014
• Actual Primary Completion Date: Apr 1, 2019
• Actual Study Completion Date: Apr 1, 2019

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

1. Incidence of NEC [At 36 weeks of corrected age]

   To compare the incidence of NEC between EPO group and control group at 36 weeks of corrected age

Secondary Outcome Measures

1. Incidence of low height in patients with NEC [At corrected age of 18 months]

   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.

2. Incidence of low weight in patients with NEC [At corrected age of 18 months]

   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.

3. Incidence of low head circumference in patients with NEC [At corrected age of 18 months]

   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.

4. Incidence of MDI<70 in patients with NEC [At corrected age of 18 months]

   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.

5. Incidence of cerebral palsy in patients with NEC [At corrected age of 18 months]

   To compare the incidence of cerebral palsy in patients with NEC between EPO and control group at 18 months of corrected age.

6. Incidence of blindness in patients with NEC [At corrected age of 18 months]

   To compare the incidence of blindness in patients with NEC between EPO and control group via visual acuity at 18 months of corrected age.

7. Incidence of deafness in patients with NEC [At corrected age of 18 months]

   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.

8. The effect of EPO treatment on blood messenger RNA (mRNA) expression [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

Criteria

• Ages Eligible for Study: N/A to 72 Hours
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Third Affiliated Hospital of Zhengzhou University	Zhengzhou	Henan	China	450052

Sponsors and Collaborators

• Zhengzhou University
• Zhengzhou Children's Hospital, China
• The First Affiliated Hospital of Zhengzhou University
• Women and Children Health Care Center of Luoyang, China
• Göteborg University

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Changlian Zhu, Director, Clinical research center of Third Affiliated Hospitial, Zhengzhou University
• ClinicalTrials.gov Identifier: NCT03919500
• Other Study ID Numbers: HN-2014002
• First Posted: Apr 18, 2019
• Last Update Posted: Apr 19, 2019
• Last Verified: Apr 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Changlian Zhu, Director, Clinical research center of Third Affiliated Hospitial, Zhengzhou University: Preterm infant; Necrotizing enterocolitis; Erythropoietin; Neurodevelopment
• Additional relevant MeSH terms: Enterocolitis; Enterocolitis, Necrotizing

Study Results

No Results Posted as of Apr 19, 2019