PAEAN - Erythropoietin for Hypoxic Ischaemic Encephalopathy in Newborns

NCT03079167 | Completed Phase 3 DMC

• 2 other identifiers: CTC011912614000669695
• Study Type: interventional
• Target: 313
• Locations: 3 countries
• Sites: 24

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.

Conditions

Hypoxic-Ischemic Encephalopathy

Outcome Measures

Primary Outcomes (1)

• 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

  2 years of age

Secondary Outcomes (11)

• Death

  Any time from Day 1 of treatment to 2 years of age

• Cerebral palsy (CP), assessed by paediatric assessment

  2 years of age

• Moderate/severe motor deficit

  2 years of age

• Moderate/severe cognitive deficit

  2 years of age

• Need for supplemental respiratory support (includes tracheostomy, ventilator, high flow nasal cannula, CPAP or oxygen dependency)

  2 years of age

Other Outcomes (1)

• Distribution of overall disability

  2 years of age

Study Arms (2)

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

Drug: Epoetin Alfa

Placebo

PLACEBO COMPARATOR

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

Drug: Normal saline

Interventions

Epoetin Alfa DRUG

Also known as: Epogen, Procrit

Erythropoietin

Normal saline DRUG

Also known as: 0.9% NaCl

Placebo

Eligibility Criteria

• Age: Up to 23 Hours
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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:
• out of 6 modified Sarnat criteria indicating moderate/severe encephalopathy, OR
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Sydney: lead
• National Health and Medical Research Council, Australia: collaborator

Study Sites (24)

Canberra Hospital

Garran, Australian Capital Territory, 2605, Australia

Location

Royal Prince Alfred Hospital

Camperdown, New South Wales, 2050, Australia

Location

Nepean Hospital

Kingswood, New South Wales, 2747, Australia

Location

John Hunter Hospital

New Lambton, New South Wales, 2305, Australia

Location

Royal Hospital for Women

Randwick, New South Wales, 2031, Australia

Location

Royal North Shore Hospital

St Leonards, New South Wales, 2065, Australia

Location

Westmead Hospital

Westmead, New South Wales, 2145, Australia

Location

Royal Women's & Brisbane Hospital

Herston, Queensland, 4006, Australia

Location

Mater Mothers' Hospital

South Brisbane, Queensland, 4101, Australia

Location

Flinders Medical Centre

Bedford Park, South Australia, 5042, Australia

Location

Women's and Children's Hospital

North Adelaide, South Australia, 5006, Australia

Location

Royal Hobart Hospital

Hobart, Tasmania, 7000, Australia

Location

Monash Medical Centre

Clayton, Victoria, 3168, Australia

Location

Mercy Hospital for Women

Heidelberg, Victoria, 3084, Australia

Location

The Royal Children's Hospital

Parkville, Victoria, 3052, Australia

Location

The Royal Women's Hospital

Parkville, Victoria, 3052, Australia

Location

King Edward Memorial Hospital

Subiaco, Western Australia, 6008, Australia

Location

Princess Margaret Hospital

Subiaco, Western Australia, 6008, Australia

Location

Auckland City Hospital

Auckland, 1023, New Zealand

Location

Middlemore Hospital

Auckland, 2104, New Zealand

Location

Christchurch Hospital

Christchurch, 8140, New Zealand

Location

Waikato Hospital

Hamilton, 3204, New Zealand

Location

Wellington Hospital

Wellington, 6021, New Zealand

Location

KK Women's and Children's Hospital

Singapore, 229899, Singapore

Location

MeSH Terms

Conditions

Hypoxia-Ischemia, Brain

Interventions

Epoetin Alfa; Saline Solution

Condition Hierarchy (Ancestors)

Brain Ischemia; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Hypoxia, Brain; Vascular Diseases; Cardiovascular Diseases; Hypoxia; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Erythropoietin; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Helen Liley, BHB, MBChB

  University of Sydney

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 20, 2017
• First Posted: March 14, 2017
• Study Start: May 14, 2016
• Primary Completion: November 30, 2023
• Study Completion: April 30, 2024
• Last Updated: June 5, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

AU (18); NZ (5); SG (1)