Erythropoietin in Premature Infants to Prevent Encephalopathy

NCT02550054 | Terminated Phase 2 DMC

• 1 other identifier: CHFudanU_NNICU4
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 1

Brief Summary

The main goal of this trial is to investigate whether early administration of human erythropoietin (EPO) in preterm infants improves neurodevelopmental outcome at 18 months corrected age. This study is designed as randomized, double-masked, placebo controlled multicenter study involving at least 312 patients.

Conditions

Premature Infant

Outcome Measures

Primary Outcomes (2)

• Neurodevelopment(Bayley Scores)

  To evaluate neurodevelopmental function via Bayley Scores of Infant Development Mental Development Index (BSID) and gain incidence of MDI\<70(Severe) or MDI\<85(Moderate).

  At corrected age of 18 months

• Neurological Evaluation(GMFM-88 Scores)

  To gain changes in standardized gross motor function using GMFM (Gross Motor Function Measure) as a standardized measurement tool for assessing Gross Motor Function consisting of sub-scales, lying \& rolling, sitting, crawling \& kneeling, standing, walking, running \& jumping (range: 0\~100 , Higher value means better gross motor function).

  At corrected age of 18 months

Secondary Outcomes (16)

• Brain Structural Alterations(MRI)

  At corrected age of 9 months

• Brain Structural Alterations(MRI)

  At corrected age of 18 months

• Intracranial Hemorrhage(MRI)

  At corrected age of 9 months

• Intracranial Hemorrhage(MRI)

  At corrected age of 18 months

• Brain Parenchyma Alterations(MRI)

  At corrected age of 9 months

Study Arms (2)

Erythropoietin

EXPERIMENTAL

Epo is administered 1000 U/kg, iv in 48 hours after premature birth, and at 48 hours interval for 3 doses per week. After 6 doses, Subcutaneously 3 doses per week until at corrected age of 34 weeks.

Drug: Epo

Normal saline

PLACEBO COMPARATOR

Normal saline is administered 5ml, iv at 3 to 6 hours after premature birth, and at 48 hours interval for 3 doses per week. After 6 doses, Subcutaneously 3 doses per week until at corrected age of 34 weeks.

Drug: Normal saline

Interventions

Epo DRUG

Epo is administered 1000 U/kg, iv in 48 hours after premature birth, and at 48 hours interval for 3 doses per week. After 6 doses, subcutaneously 400 U/Kg per injection and 3 doses per week until at corrected age of 34 weeks.

Also known as: Epoietin Beta

Erythropoietin

Normal saline DRUG

Normal saline is administered 5ml, iv at 3 to 6 hours after premature birth, and at 48 hours interval for 3 doses per week. After 6 doses, Subcutaneously 3 doses per week until at corrected age of 34 weeks.

Also known as: N/S solution

Normal saline

Eligibility Criteria

• Age: Up to 48 Hours
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Birthweight less or equal 1500 grams
• Less than 32 weeks gestation at birth
• Less than 48 hours of life at time of enrollment
• Written informed consent of parent or guardian

You may not qualify if:

• Intrauterine Growth Retardation
• Severe Congenital Anomalies adversely affecting life expectancy or neurodevelopment
• Genetic Metabolic Diseases
• Seizures within first 24 hours of life
• Severe neutropenia (ANC \< 500 cells/microL) within first 24 hours of life
• Polycythemia (Hct \> 65%) within first 24 hours of life
• Thrombocytopenia (platelets \< 50K cells/microL) within first 24 hours of life
• Hypertension (SBP \> 100mmHg) without vasopressor support within first 24 hours of life
• Microcephaly
• Grade III-IV intracranial hemorrhage
• Termination
• Required by parent or guardian;
• Polycythemia through blood transfusion can not be relieved
• Oliguria（\<0.5mL/kg/h for at least 24 hours）
• Progression of azotemia

Sponsors & Collaborators

• Children's Hospital of Fudan University: lead
• Xiamen Children's Hospital, Fujian of China: collaborator
• Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region: collaborator
• Guangzhou Women and Children's Medical Center: collaborator
• Second Affiliated Hospital of Wenzhou Medical University: collaborator
• Maternal and Child Health Hospital of Hubei Province: collaborator
• The Maternal & Children Health Hospital of Dehong, Yunnan of China: collaborator

Study Sites (1)

Children Hospital of Fudan University

Shanghai, Shanghai Municipality, 201102, China

Location

Related Publications (4)

• Leuchter RH, Gui L, Poncet A, Hagmann C, Lodygensky GA, Martin E, Koller B, Darque A, Bucher HU, Huppi PS. Association between early administration of high-dose erythropoietin in preterm infants and brain MRI abnormality at term-equivalent age. JAMA. 2014 Aug 27;312(8):817-24. doi: 10.1001/jama.2014.9645.

  PMID: 25157725 BACKGROUND

• Dame C, Langer J, Koller BM, Fauchere JC, Bucher HU. Urinary erythropoietin concentrations after early short-term infusion of high-dose recombinant epo for neuroprotection in preterm neonates. Neonatology. 2012;102(3):172-7. doi: 10.1159/000339283. Epub 2012 Jul 4.

  PMID: 22776958 BACKGROUND

• Kuki I, Kawawaki H, Horino A, Inoue T, Nukui M, Okazaki S, Tomiwa K, Amo K, Togawa M, Shiomi M. [A clinical study on high-dose erythropoietin therapy for acute encephalopathy or encephalitis]. No To Hattatsu. 2015 Jan;47(1):32-6. Japanese.

  PMID: 25803909 BACKGROUND

• Traudt CM, McPherson RJ, Bauer LA, Richards TL, Burbacher TM, McAdams RM, Juul SE. Concurrent erythropoietin and hypothermia treatment improve outcomes in a term nonhuman primate model of perinatal asphyxia. Dev Neurosci. 2013;35(6):491-503. doi: 10.1159/000355460. Epub 2013 Nov 1.

  PMID: 24192275 BACKGROUND

MeSH Terms

Conditions

Premature Birth

Interventions

Eosinophil Peroxidase; Saline Solution

Condition Hierarchy (Ancestors)

Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Intervention Hierarchy (Ancestors)

Peroxidases; Oxidoreductases; Enzymes; Enzymes and Coenzymes; Eosinophil Granule Proteins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Wenhao Zhou, Doctor

  Children's Hospital of Fudan University

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 4, 2015
• First Posted: September 15, 2015
• Study Start: September 8, 2015
• Primary Completion: December 30, 2016
• Study Completion: December 30, 2016
• Last Updated: December 29, 2023

Record last verified: 2023-12

Locations

CN (1)