Neurological Outcome After Erythropoietin Treatment for Neonatal Encephalopathy

Phase 1

Completed

• Conditions: Hypoxic-Ischemic Encephalopathy

• Registration Number: NCT00808704
• Lead Sponsor: Zhengzhou University

Brief Summary

Perinatal asphyxia-induced brain injury is one of the most common causes of morbidity and mortality in term and preterm neonates, accounting for 23% of neonatal deaths globally. Although many neuroprotective strategies appeared promising in animal models, most of them have failed clinically. Erythropoietin (EPO) is an endogenous cytokine originally identified for its role in erythropoiesis. Clinical trial has demonstrated the safety and efficacy of recombinant human erythropoietin (r-hu-EPO) in the prevention or treatment of anemia of prematurity. To date, there are no reports evaluating possible effects of EPO on neonatal HIE.

Detailed Description

Hypoxic-ischemic encephalopathy of the newborn infant remains a significant socio-economic health problem worldwide. Moderate to severe HIE of newborn infants is associated with a high rate of death or long-term disabilities. Historically, treatment has been purely supportive including stabilizing cardio-respiratory functions and treating convulsions.Recent multi-center trials assessing the effects of hypothermia demonstrated improved outcome in term neonates with moderate hypoxic-ischemic encephalopathy (HIE). However, hypothermia was not effective beyond 6 hrs after brain injury.

Systemically administered EPO was neuroprotective in neonatal brain injury models. Clinical study on adult stroke showed improved outcome. However, treating HIE with EPO raises a series of questions such as: i) Can the patient population of this study readily be compared with those in the hypothermia trials? ii) What are the pharmacokinetics of EPO, including issues of dosage and timing, and does administered EPO cross the blood-brain-barrier? iii) How does the effectiveness, side effects and potentials of EPO therapy compare with induced hypothermia?

Study Timeline

• Study Start: 2003-08
• Primary Completion: 2008-07
• Study Completion: 2008-07
• Status Verified: 2008-12
• Study First Submitted: 2008-12-15
• Study First Submitted QC: 2008-12-15
• Last Update Submitted: 2008-12-15
• Study First Posted: 2008-12-16
• Last Update Posted: 2008-12-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 167

Inclusion Criteria

• Apgar score of 5 or less at 5 min after birth or continued need for resuscitation, including endotracheal or mask ventilation at 10 min after birth.
• The severity of encephalopathy, moderate or severe, was assessed by certified examiners according to the criteria of Sarnat and Sarnat(13), consisting of altered state of consciousness: lethargy, stupor or coma, and at least one or more of hypotonia, abnormal reflexes including oculomotor or pupillary abnormalities, absent or weak sucking or clinical seizures.

Exclusion Criteria

• Major congenital abnormalities, head trauma or skull fracture causing major intracranial hemorrhage, mild HIE, financial problems of the parents, lack of permanent address or postnatal age > 48 hrs

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Mortality and disability rate. Mortality and disability rate at 18months of age.	18 months

Trial Locations

Locations (1)

NICU, the Third Affiliated Hospital, Zhengzhou University; 🇨🇳 Zhengzhou, Henan, China