Efficacy of Erythropoietin to Improve Survival and Neurological Outcome in Hypoxic Ischemic Encephalopathy (Neurepo)

Phase III Study of Efficacy of High Dose Erythropoietin to Prevent Hypoxic-ischemic Encephalopathy Sequelae in Term Newborn

The purpose of this study is to determine the efficacy of high dose Erythropoietin to improve survival and neurologic outcome in asphyxiated term newborn undergoing cooling.

Study Overview

• Status: Completed
• Conditions: Hypoxic Ischemic Encephalopathy
• Intervention / Treatment: Drug: Placebo; Drug: erythropoietin Beta

Detailed Description

Hypoxic-ischemic encephalopathy remains the main cause of death or long term neurologic impairments in neonates. Yet, therapies for birth asphyxia are currently limited. Hypothermia when applied within 6 hours after birth demonstrate partial improvement in outcome of newborns specially those with moderate form. Erythropoietin and its receptors are upregulated after brain injury in ischemic conditions. Systemically administered erythropoietin is neuroprotective in animal models of birth asphyxia. To date, one study demonstrate improvement neurologic outcome in asphyxiated term newborn under erythropoietin treatment but no reports evaluating beneficial of erythropoietin associated with cooling. This is a large randomised controlled trial to evaluate the efficacy of high dose erythropoietin on outcome at two years of asphyxiated term newborns undergoing cooling.

• Study Type: Interventional
• Enrollment (Actual): 120
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Paris, France, 75014
    • Cochin Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 1 year (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Term or near-term newborn (> = 36 weeks gestational age)
• Moderate to severe encephalopathy
• undergoing moderate controlled hypothermia started within 6 hours after delivery : rectal or esophageal temperature maintained at 33.5 ° C + / - 0.5 ° C before H6
• Beneficiary of social security plan
• Informed consent parental authority

Exclusion Criteria:

• Impossibility of getting controlled hypothermia before H6
• Infant older than 12 hours of age
• Chromosomal or significant congenital abnormality
• Predictable surgery in the first 3 days of life
• Uncontrolled collapse
• Haemorrhagic syndrome unchecked
• Head trauma with or without skull fracture

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Erythropoietin beta; 1000 to 1500 U/kg/dose X 3 every 24 hours	Drug: erythropoietin Beta; erythropoietin intravenous injection (5000 U/ 0.3 ml)1000 to 1500 U/kg/dose X 3 given every 24 hours with the first dose within 12 hours of delivery
Placebo Comparator: Placebo; 0.2 ml saline solution X 3 given every 24 hours	Drug: Placebo; Other Names: 0.2 ml saline solution X 3 given every 24 hours with the first dose within 12 hours of delivery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Survival without neurologic sequelae	at 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality rates	number of dead patients	Within 24 months
Rate of moderate and severe sequelae	Mental Developmental index (Brunet Lezine Test), motor, visual and hearing impairment	at 24 months
Aspect of brain lesions on MRI	Brain MRI performed between day 6 and day 12 after birth	at day 6 and day 12 after birth
Tolerance of treatment		at 24 months

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Principal Investigator: Juliana Patkai, MD, PhD, Cochin Hospital

Publications and helpful links

General Publications

• Zhu C, Kang W, Xu F, Cheng X, Zhang Z, Jia L, Ji L, Guo X, Xiong H, Simbruner G, Blomgren K, Wang X. Erythropoietin improved neurologic outcomes in newborns with hypoxic-ischemic encephalopathy. Pediatrics. 2009 Aug;124(2):e218-26. doi: 10.1542/peds.2008-3553. Epub 2009 Jul 27.
• Goodarzi MO, Carmina E, Azziz R. DHEA, DHEAS and PCOS. J Steroid Biochem Mol Biol. 2015 Jan;145:213-25. doi: 10.1016/j.jsbmb.2014.06.003. Epub 2014 Jul 5.

Study record dates

Study Major Dates

• Study Start (Actual): March 28, 2013
• Primary Completion (Actual): February 14, 2017
• Study Completion (Actual): February 14, 2017

Study Registration Dates

• First Submitted: November 19, 2012
• First Submitted That Met QC Criteria: November 19, 2012
• First Posted (Estimate): November 22, 2012

Study Record Updates

• Last Update Posted (Actual): May 3, 2021
• Last Update Submitted That Met QC Criteria: April 30, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: erythropoietin; Hypoxic Ischemic Encephalopathy; Neuroprotection; Term neonate
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Central Nervous System Diseases; Nervous System Diseases; Signs and Symptoms, Respiratory; Hypoxia, Brain; Brain Ischemia; Ischemia; Brain Diseases; Hypoxia; Hypoxia-Ischemia, Brain; Hematinics; Epoetin Alfa
• Other Study ID Numbers: P110111; 2012-001417-17 (EudraCT Number)