PAEAN - Erythropoietin for Hypoxic Ischaemic Encephalopathy in Newborns

University of Sydney

Status and phase

Completed

Phase 3

Conditions

Hypoxic-Ischemic Encephalopathy

Treatments

Drug: Normal saline

Drug: Epoetin Alfa

Study type

Interventional

Funder types

Other

Identifiers

NCT03079167

12614000669695 (Registry Identifier)

CTC0119

Details and patient eligibility

About

Double-blind, placebo controlled Phase III trial of erythropoietin for hypoxic ischaemic encephalopathy in infants receiving hypothermia. The study aim is to determine whether Epo in conjunction with hypothermia in infants with moderate/severe hypoxic ischaemic encephalopathy (HIE) will improve neurodevelopmental outcomes at 2 years of age, without significant adverse effects, when compared to hypothermia alone.

Full description

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 near-term 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.

Enrollment

313 patients

Sex

All

Ages

Under 23 hours old

Volunteers

No Healthy Volunteers

Inclusion criteria

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 indicators of perinatal depression:
1. Apgar less than or equal to 5 at 10 minutes after birth, OR
2. Receiving ongoing resuscitation e.g. assisted ventilation (positive pressure ventilation or CPAP) or chest compressions at 10 minutes after birth, OR
3. on cord blood or arterial or venous blood obtained at less than 60 minutes after birth, either pH less than 7.00 OR base deficit greater than or equal to 12.0 mmol/L
Moderate to severe encephalopathy, defined between one and six hours after birth by one or both of the following:
1. 3 out of 6 modified Sarnat criteria indicating moderate/severe encephalopathy, OR
2. 2 out of 6 modified Sarnat criteria plus seizure(s) requiring anticonvulsant treatment (diagnosed either clinically or using EEG monitoring) at any time prior to randomisation
Hypothermia treatment initiated by 6 hours ofa ge; i.e. controlled whole-body cooling planned to continue for 72 hours to a target temperature (adjusted manually or with a device) and subsequent controlled re-warming
Study treatment planned to start within 24 hours after birth (as soon as feasible after randomisation)
At least 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 criteria

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