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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03079167




Registration number
NCT03079167
Ethics application status
Date submitted
20/02/2017
Date registered
14/03/2017
Date last updated
28/04/2021

Titles & IDs
Public title
PAEAN - Erythropoietin for Hypoxic Ischaemic Encephalopathy in Newborns
Scientific title
Preventing Adverse Outcomes of Neonatal Hypoxic Ischaemic Encephalopathy With Erythropoietin: A Phase III Randomised Placebo Controlled Multicentre Clinical Trial
Secondary ID [1] 0 0
12614000669695
Secondary ID [2] 0 0
CTC0119
Universal Trial Number (UTN)
Trial acronym
PAEAN
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hypoxic-Ischemic Encephalopathy 0 0
Condition category
Condition code
Cardiovascular 0 0 0 0
Diseases of the vasculature and circulation including the lymphatic system
Neurological 0 0 0 0
Other neurological disorders
Respiratory 0 0 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Epoetin Alfa
Treatment: Drugs - Normal saline

Experimental: Erythropoietin - Erythropoietin (epoetin alfa) 1000 IU/kg birth weight (capped at 4000IU daily) IV infusion, on Days 1, 2, 3, 5 and 7 of age

Placebo Comparator: Placebo - IV normal saline (equiv. volume), on Days 1, 2, 3, 5 and 7 of age


Treatment: Drugs: Epoetin Alfa


Treatment: Drugs: Normal saline


Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Composite measure of death or moderate/severe disability - Moderate/severe disability is defined as any cerebral palsy and a Gross Motor Function Classification Scale (GMFCS) score greater than or equal to 1), or Bayley Scale of Infant Development III (BSDIII) less than or equal to 80
Timepoint [1] 0 0
2 years of age
Secondary outcome [1] 0 0
Death
Timepoint [1] 0 0
Any time from Day 1 of treatment to 2 years of age
Secondary outcome [2] 0 0
Cerebral palsy (CP), assessed by paediatric assessment
Timepoint [2] 0 0
2 years of age
Secondary outcome [3] 0 0
Moderate/severe motor deficit - Composite of any incidence of CP (any of quadriparesis, CP, hemiparesis or diparesis) AND any level of functional impairment using the GMFCS greater than or equal to 1.0
Timepoint [3] 0 0
2 years of age
Secondary outcome [4] 0 0
Moderate/severe cognitive deficit - Defined as a BSDIII cognitive score less than or equal to 80
Timepoint [4] 0 0
2 years of age
Secondary outcome [5] 0 0
Need for supplemental respiratory support (includes tracheostomy, ventilator, high flow nasal cannula, CPAP or oxygen dependency)
Timepoint [5] 0 0
2 years of age
Secondary outcome [6] 0 0
Need for nutritional support (includes gastrostomy or nasogastric feeds)
Timepoint [6] 0 0
2 years of age
Secondary outcome [7] 0 0
Major cortical visual impairment by paediatric examination
Timepoint [7] 0 0
2 years of age
Secondary outcome [8] 0 0
Hearing impairment status by paediatric examination - requirement for hearing aids
Timepoint [8] 0 0
2 years of age
Secondary outcome [9] 0 0
Autism spectrum disorder, assessed by Modified Checklist for Autism in Toddlers (M-CHAT) parent questionnaire
Timepoint [9] 0 0
2 years of age
Secondary outcome [10] 0 0
Epilepsy (history of 2 or more afebrile unprovoked seizures since discharge from neonatal unit where PAEAN study treatment was provided, or use of anticonvulsants at 2 years of age).
Timepoint [10] 0 0
2 years of age
Secondary outcome [11] 0 0
Cost of healthcare and service utilisation - Defined as a composite of parent completed questionnaire data and Medicare service use
Timepoint [11] 0 0
2 years of age
Secondary outcome [12] 0 0
Frequency of selected adverse events (AEs) of interest, including deaths
Timepoint [12] 0 0
Up to 30 days post study treatment

Eligibility
Key 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
Minimum age
No limit
Maximum age
23 Hours
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
ACT,NSW,QLD,SA,TAS,VIC,WA
Recruitment hospital [1] 0 0
Canberra Hospital - Garran
Recruitment hospital [2] 0 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [3] 0 0
Nepean Hospital - Kingswood
Recruitment hospital [4] 0 0
John Hunter Hospital - New Lambton
Recruitment hospital [5] 0 0
Royal Hospital for Women - Randwick
Recruitment hospital [6] 0 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [7] 0 0
Westmead Hospital - Westmead
Recruitment hospital [8] 0 0
Royal Women's & Brisbane Hospital - Herston
Recruitment hospital [9] 0 0
Mater Mothers' Hospital - South Brisbane
Recruitment hospital [10] 0 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [11] 0 0
Women's and Children's Hospital - North Adelaide
Recruitment hospital [12] 0 0
Royal Hobart Hospital - Hobart
Recruitment hospital [13] 0 0
Monash Medical Centre - Clayton
Recruitment hospital [14] 0 0
Mercy Hospital for Women - Heidelberg
Recruitment hospital [15] 0 0
The Royal Children's Hospital - Parkville
Recruitment hospital [16] 0 0
The Royal Women's Hospital - Parkville
Recruitment hospital [17] 0 0
King Edward Memorial Hospital - Subiaco
Recruitment hospital [18] 0 0
Princess Margaret Hospital - Subiaco
Recruitment postcode(s) [1] 0 0
2605 - Garran
Recruitment postcode(s) [2] 0 0
2050 - Camperdown
Recruitment postcode(s) [3] 0 0
2747 - Kingswood
Recruitment postcode(s) [4] 0 0
2305 - New Lambton
Recruitment postcode(s) [5] 0 0
2031 - Randwick
Recruitment postcode(s) [6] 0 0
2065 - St Leonards
Recruitment postcode(s) [7] 0 0
2145 - Westmead
Recruitment postcode(s) [8] 0 0
4006 - Herston
Recruitment postcode(s) [9] 0 0
4101 - South Brisbane
Recruitment postcode(s) [10] 0 0
5042 - Bedford Park
Recruitment postcode(s) [11] 0 0
5006 - North Adelaide
Recruitment postcode(s) [12] 0 0
7000 - Hobart
Recruitment postcode(s) [13] 0 0
3168 - Clayton
Recruitment postcode(s) [14] 0 0
3084 - Heidelberg
Recruitment postcode(s) [15] 0 0
3052 - Parkville
Recruitment postcode(s) [16] 0 0
6008 - Subiaco
Recruitment outside Australia
Country [1] 0 0
New Zealand
State/province [1] 0 0
Auckland
Country [2] 0 0
New Zealand
State/province [2] 0 0
Christchurch
Country [3] 0 0
New Zealand
State/province [3] 0 0
Hamilton
Country [4] 0 0
New Zealand
State/province [4] 0 0
Wellington
Country [5] 0 0
Singapore
State/province [5] 0 0
Singapore

Funding & Sponsors
Primary sponsor type
Other
Name
University of Sydney
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
National Health and Medical Research Council, Australia
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
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.
Trial website
https://clinicaltrials.gov/show/NCT03079167
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Helen Liley, BHB, MBChB
Address 0 0
University of Sydney
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications