Hypoxic-Ischemic EncephalopathyPhase 3PAEANNCT03079167
PAEAN - Erythropoietin for Hypoxic Ischaemic Encephalopathy in Newborns
A Phase 3 study testing Epoetin Alfa and Normal saline in people with Hypoxic-Ischemic Encephalopathy, run by University of Sydney at 24 sites in 3 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages Up to 23 hours
- Conditions the study is for
- Hypoxic-Ischemic Encephalopathy
- What is being tested?
- Epoetin Alfa and Normal saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 313 participants
- Where
- 24 sitesin 3 countries
- Study dates
- 14 May 2016to 30 Apr 2024
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 23 hours
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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:
- Apgar less than or equal to 5 at 10 minutes after birth, OR
- Receiving ongoing resuscitation e.g. assisted ventilation (positive pressure ventilation or CPAP) or chest compressions at 10 minutes after birth, OR
- 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:
Show all 13Show fewer
- 3 out of 6 modified Sarnat criteria indicating moderate/severe encephalopathy, OR
- 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
Who cannot join
- 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
Trial locations and contacts
24 sites in 3 countries.
24 sites in 3 countries
Australia18 sites
Flinders Medical Centre
Bedford Park, South Australia, 5042
Royal Prince Alfred Hospital
Camperdown, New South Wales, 2050
Monash Medical Centre
Clayton, Victoria, 3168
Canberra Hospital
Garran, Australian Capital Territory, 2605
Mercy Hospital for Women
Heidelberg, Victoria, 3084
Royal Women's & Brisbane Hospital
Herston, Queensland, 4006
Royal Hobart Hospital
Hobart, Tasmania, 7000
Nepean Hospital
Kingswood, New South Wales, 2747
John Hunter Hospital
New Lambton, New South Wales, 2305
Women's and Children's Hospital
North Adelaide, South Australia, 5006
The Royal Children's Hospital
Parkville, Victoria, 3052
The Royal Women's Hospital
Parkville, Victoria, 3052
Royal Hospital for Women
Randwick, New South Wales, 2031
Mater Mothers' Hospital
South Brisbane, Queensland, 4101
Royal North Shore Hospital
St Leonards, New South Wales, 2065
King Edward Memorial Hospital
Subiaco, Western Australia, 6008
Princess Margaret Hospital
Subiaco, Western Australia, 6008
Westmead Hospital
Westmead, New South Wales, 2145
New Zealand5 sites
Auckland City Hospital
Auckland, 1023
Middlemore Hospital
Auckland, 2104
Christchurch Hospital
Christchurch, 8140
Waikato Hospital
Hamilton, 3204
Wellington Hospital
Wellington, 6021
About this study
Official title: Preventing Adverse Outcomes of Neonatal Hypoxic Ischaemic Encephalopathy With Erythropoietin: A Phase III Randomised Placebo Controlled Multicentre Clinical Trial
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.
Read the detailed 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.
- Conditions
- Hypoxic-Ischemic Encephalopathy
- Being tested
- Epoetin Alfa, Normal saline
- Medical subject headings
- Hypoxia-Ischemia, Brain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Epoetin AlfaDrug
Also called Epogen, Procrit
Normal salineDrug
Also called 0.9% NaCl
| Study group | Role | What they receive |
|---|---|---|
| Erythropoietin | Experimental | Erythropoietin (epoetin alfa) 1000 IU/kg birth weight (capped at 4000IU daily) IV infusion, on Days 1, 2, 3, 5 and 7 of age Receives: Drug: Epoetin Alfa |
| Placebo | Placebo comparator | IV normal saline (equiv. volume), on Days 1, 2, 3, 5 and 7 of age Receives: Drug: Normal saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 2 years of age
Secondary outcomes (11)
Death
Death from any cause
Measured: Any time from Day 1 of treatment to 2 years of age
Cerebral palsy (CP), assessed by paediatric assessment
Any incidence of CP (any of quadriplegia, triplegia, hemiplegia, diplegia or monoplegia)
Measured: 2 years of age
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
Measured: 2 years of age
Moderate/severe cognitive deficit
Defined as a BSDIII cognitive score less than or equal to 80
Measured: 2 years of age
Need for supplemental respiratory support (includes tracheostomy, ventilator, high flow nasal cannula, CPAP or oxygen dependency)
Supplemental respiratory support includes tracheostomy, ventilator, high flow nasal cannula, CPAP or oxygen dependency
Measured: 2 years of age
Need for nutritional support (includes gastrostomy or nasogastric feeds)
Nutritional support includes gastrostomy or nasogastric feeds
Measured: 2 years of age
Major cortical visual impairment by paediatric examination
Impairment as assessed by paediatric assessment
Measured: 2 years of age
Hearing impairment status by paediatric examination - requirement for hearing aids
Defined as the requirement for hearing aids (either diagnosis of: Hears well or with only a little difficulty WITH a hearing aid OR Has severe hearing difficulty even with a hearing aid or hearing is not helped with an aid)
Measured: 2 years of age
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).
Defined by 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
Measured: 2 years of age
Cost of healthcare and service utilisation
Defined as a composite of parent completed questionnaire data and Medicare service use
Measured: 2 years of age
Frequency of selected adverse events (AEs) of interest, including deaths
Frequency of selected adverse events (AEs) of interest up to 30 days after the last study dose
Measured: Up to 30 days post study treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Mar 2017
- Study start14 May 2016
- Primary completion30 Nov 2023
- Study completion30 Apr 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hypoxic-Ischemic EncephalopathyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 313 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Sydney
- Sponsor type
- University, hospital or other
- Collaborators
- National Health and Medical Research Council, Australia
- Responsible party
- Sponsor
- Investigators
- Helen Liley, BHB, MBChB, Study chair, University of Sydney
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03079167
- Sponsor's protocol ID
- CTC0119
- Other IDs
- 12614000669695
- Acronym
- PAEAN
- Status last verified
- Jun 2024
- First submitted
- 20 Feb 2017
- Last updated
- 5 Jun 2024
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Preventing Adverse Outcomes of Neonatal Hypoxic Ischaemic Encephalopathy With Erythropoietin: A Phase III Randomised Placebo Controlled Multicentre Clinical Trial
- ClinicalTrials.gov ID
- NCT03079167
- Acronym / sponsor ID
- PAEAN / CTC0119
- Conditions
- Hypoxic-Ischemic Encephalopathy
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 313 participants (actual)
- Lead sponsor
- University of SydneyUniversity, hospital or other
- Collaborators
- National Health and Medical Research Council, Australia
- Study start
- 14 May 2016 (actual)
- Primary completion
- 30 Nov 2023 (actual)
- Study completion
- 30 Apr 2024 (actual)
- First posted
- 14 Mar 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Erythropoietin | Experimental | Drug: Epoetin AlfaErythropoietin (epoetin alfa) 1000 IU/kg birth weight (capped at 4000IU daily) IV infusion, on Days 1, 2, 3, 5 and 7 of age |
| Placebo | Placebo comparator | Drug: Normal salineIV normal saline (equiv. volume), on Days 1, 2, 3, 5 and 7 of age |
Who may qualify
- Ages
- Up to 23 hours
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (13 listed)
- 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:
- Moderate to severe encephalopathy, defined between one and six hours after birth by one or both of the following:
- 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)
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Epoetin AlfaAlso: Epogen, Procrit | Drug | Erythropoietin |
| Normal salineAlso: 0.9% NaCl | Drug | Placebo |
Primary outcome
Composite measure of death or moderate/severe disability
Time frame: 2 years of age
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
11 secondary outcomes
Death
Time frame: Any time from Day 1 of treatment to 2 years of age
Cerebral palsy (CP), assessed by paediatric assessment
Time frame: 2 years of age
Moderate/severe motor deficit
Time frame: 2 years of age
Moderate/severe cognitive deficit
Time frame: 2 years of age
Need for supplemental respiratory support (includes tracheostomy, ventilator, high flow nasal cannula, CPAP or oxygen dependency)
Time frame: 2 years of age
Need for nutritional support (includes gastrostomy or nasogastric feeds)
Time frame: 2 years of age
Major cortical visual impairment by paediatric examination
Time frame: 2 years of age
Hearing impairment status by paediatric examination - requirement for hearing aids
Time frame: 2 years of age
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).
Time frame: 2 years of age
Cost of healthcare and service utilisation
Time frame: 2 years of age
Frequency of selected adverse events (AEs) of interest, including deaths
Time frame: Up to 30 days post study treatment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jun 2024.
- Individual participant dataSharing planned: No
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Levetiracetam as an Adjuvant Therapy to Hypothermia in Neonatal Asphyxia
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Minimal Sedation Versus Standard Continuous Sedation After Out-of-Hospital Cardiac Arrest
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Neuro-MoD: Neuroplasticity With Motor Development
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Helen Liley, BHB, MBChB study chair
University of Sydney
24 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Epoetin Alfa and Normal saline in people with Hypoxic-Ischemic Encephalopathy, run by University of Sydney at 24 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 24 sites in Australia, New Zealand, Singapore. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Composite measure of death or moderate/severe disability (time frame: 2 years of age). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jun 2024.