CompletedPhase 3ACTRN12614000669695

PAEAN – Erythropoietin for hypoxic ischaemic encephalopathy in newborns

Preventing Adverse Outcomes of Neonatal Hypoxic Ischaemic Encephalopathy with Erythropoietin: A Phase III Randomised Placebo Controlled Multicentre Clinical Trial

Sponsor

University of Sydney

Enrollment

300 participants

Start Date

May 14, 2016

Study Type

Interventional

Conditions

neonatal hypoxic ischaemic encephalopathy

Summary

A lack of oxygen (hypoxia) or low blood supply (ischaemia) before or during birth can destroy cells in a newborn baby's brain. The damage caused by the lack of oxygen continues for some time afterwards. One way to try to reduce this damage is to induce hypothermia cooling the baby or just the baby's head for hours to days. Erythropoietin (Epo) given in the first week after birth shows promise as a treatment that may also help. This study is to find out whether Epo plus induced hypothermia (cooling) of nearterm newborn babies who have suffered from low blood or oxygen supply to the brain at birth reduces death and disability in survivors at two years of age. The target population is 300 newborn term or near term infants(greater than or equal to 35+0 weeks gestation) with hypoxic ischaemic encephalopathy who are receiving, or planned to receive hypothermia and who are able to be recruited in time to allow study treatment to commence before 24 hours of age. This is a double blind, placebo controlled, parallel, 2 arm randomised, phase III multicentre trial, stratified by study site and by severity of encephalopathy at study entry. The treatment group of 150 infants will receive human recombinant Epo, 1000 IU/kg IV on days 1, 2, 3, 5 & 7 of life. The control group will receive 0.9% sodium chloride as a placebo on days 1, 2, 3, 5 & 7 of life. Families will be followed up every 6 months until the primary assessment of death and disability at 2 years of age.

Eligibility

Sex: Both males and femalesMin Age: 35 Weekss

Inclusion Criteria14

Male or female infants born greater than or equal to 35+0 weeks gestation and able to be randomised less than 23 hours after birth.
One or more of the following indications of perinatal depression:
a. Apgar less than or equal to 5 at 10 minutes after birth OR
b. receiving ongoing resuscitation eg assisted ventilation (positive pressure ventilation or CPAP) or chest compressions at 10 minutes after birth OR
c. on cord blood or arterial or venous blood obtained at less 60 minutes after birth the following values: pH less than 7.00 OR base deficit greater than or equal to 12
Moderate to severe encephalopathy, defined between one and six hours after birth by one or both of the following
a. 3 out of 6 modified Sarnat criteria indicating moderate/severe encephalopathy
OR
b. 2 out of 6 modified Sarnat criteria plus seizure(s) requiring anticonvulsant treatment (diagnosed either clinically or using EEG monitoring)
Hypothermia treatment initiated by 6 hours of age; i.e. controlled whole-body cooling for 72 hours, to a target temperature (adjusted manually or with a device) and subsequent controlled re-warming
Study treatment both planned and able to start within 24 hours after birth (as soon as feasible after randomisation)
One parent greater than or equal to 18 years of age
Anticipated ability to collect primary endpoint at 2 years of age
Signed, written informed parental consent

Exclusion Criteria6

Contraindications to investigational product
Indication prior to randomisation for erythropoietin or any other erythropoietic stimulating agent to be given during the first two weeks of life.
Severe intrauterine growth restriction (birth weight less than 1800g)
Suspected major chromosomal or congenital anomalies
Head circumference less than 3rd centile below the mean for gestation and gender.
Infant for whom imminent withdrawal of care is being planned.

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Interventions

Erythropoetin (epoetin alpha) 1000 IU/kg intravenous infusion once daily on days 1, 2, 3, 5 & 7 of life