Neurological Outcome After Erythropoietin Treatment for Neonatal Encephalopathy

Hypoxic-Ischemic Encephalopathy Clinical Trial

Official title:

Effect of Erythropoietin on Neonatal Hypoxic Ischemic Encephalopathy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00808704
• Other study ID #: HN-200312
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: December 15, 2008
• Last updated: December 15, 2008
• Start date: August 2003
• Est. completion date: July 2008

Study information

• Verified date: December 2008
• Source: Zhengzhou University
• Contact: n/a
• Is FDA regulated: No
• Health authority: China: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

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?

Recruitment information / eligibility

• Status: Completed
• Enrollment: 167
• Est. completion date: July 2008
• Est. primary completion date: July 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 48 Hours

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Brain Diseases
• Brain Ischemia
• Hypoxia-Ischemia, Brain
• Hypoxic-Ischemic Encephalopathy

Intervention

Drug:
• recombinant human erythropoietin
r-hu-EPO were administered either 300 U/kg or 500 U/kg, subcutaneously the first time and then intravenously every other day for 2 weeks.

Locations

Country	Name	City	State
China	NICU, the Third Affiliated Hospital, Zhengzhou University	Zhengzhou	Henan

Sponsors (4)

Lead Sponsor	Collaborator
Zhengzhou University	Göteborg University, Medical University Innsbruck, Zhengzhou Children's Hospital, China

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mortality and disability rate. Mortality and disability rate at 18months of age.		18 months	Yes