Does Erythropoietin Improve Outcome in Very Preterm Infants?

This study has been completed.
Sponsor:
Collaborator:
Swiss National Science Foundation
Information provided by (Responsible Party):
Bucher Hans Ulrich, Swiss Neonatal Network
ClinicalTrials.gov Identifier:
NCT00413946
First received: December 18, 2006
Last updated: August 12, 2013
Last verified: August 2013
  Purpose

The main goal of this trial is to investigate whether early administration of human erythropoietin (EPO) in very preterm infants improves neurodevelopmental outcome at 24 months corrected age.

This study is designed as randomized, double-masked, placebo-controlled multi-center study involving at least 420 patients.


Condition Intervention Phase
Intracranial Hemorrhage
Periventricular Leukomalacia
Postnatal Development
Cerebral Palsy
Drug: Recombinant human Erythropoietin
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Bio-availability Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Neuroprotective Effect of High Dose Erythropoietin in Very Preterm Infants

Resource links provided by NLM:


Further study details as provided by Swiss Neonatal Network:

Primary Outcome Measures:
  • Mental developmental index (Bayley II) and motor, visual and hearing impairment [ Time Frame: at age of 24 months corrected for prematurity. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • MRI at term equivalent [ Time Frame: 40 postmenstrual weeks ] [ Designated as safety issue: No ]
    White matter injury score grey matter injury score brain maturation

  • cerebral palsy. [ Time Frame: First 24 months of life (corrected for prematurity) ] [ Designated as safety issue: No ]

Enrollment: 420
Study Start Date: January 2006
Study Completion Date: March 2012
Primary Completion Date: March 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: rEpo
three doses of rEryhtropoietin 300 units/kg body weight
Drug: Recombinant human Erythropoietin
3 doses of rEpo, 3000 Units per kg body weight or 1 ml of saline
Placebo Comparator: saline Drug: Recombinant human Erythropoietin
3 doses of rEpo, 3000 Units per kg body weight or 1 ml of saline

Detailed Description:

HYPOTHESIS Early administration of human erythropoietin (EPO) in very preterm infants reduces perinatal injury to the brain (retina), lung and gut and improves neurodevelopmental outcome at 24 months corrected age.

PRIMARY OBJECTIVE To determine whether cerebral outcome is improved if infants born between 24 0/7 and 31 6/7 gestational weeks at birth receive erythropoietin in high dose in the first three days after birth.

SECONDARY OBJECTIVES To determine whether early administration of EPO alters the incidence of complications typically associated with preterm birth, i.e. mortality, septicaemia, necrotising enterocolitis, bronchopulmonary dysplasia (oxygen dependency at 36 weeks postmenstrual age), retinopathy, intracranial haemorrhage, white matter disease (periventricular leucomalacia), growth failure, cerebral palsy and handicap at 5 years.

RATIONALE EPO has been shown to be protective against hypoxic-ischaemic and inflammatory injuries in a broad range of tissues and organs besides promoting red cell formation. It has been shown to have neuroprotective and neurotrophic activity in animals after acute brain damage as well as in adult stroke patients. Several mechanisms explaining this activity have been recognized: EPO inhibits glutamate release in the brain, modulates intracellular calcium metabolism, induces the generation of anti-apoptotic factors, reduces inflammation, decreases nitric oxide-mediated injury, and has direct antioxidant effects.

Very preterm infants have significant delay in mental and physical development assessed at 24 months corrected age. The most critical period are the first days after preterm birth where the oxygenation of the brain may be impaired by respiratory, circulatory and nutritional insufficiency. Although there are probably several mechanisms involved in permanent brain damage, it is most likely that EPO with its multiple action may reduce this damage.

EPO has been studied in several trials in preterm infants to prevent anaemia and is now widely used for this indication.

STUDY DESIGN Randomized, double-masked, placebo-controlled multi-center clinical trial. Research plan 420 infants will be randomized during the first three hours of life to receive EPO (3000 U/kg body weight) or placebo intravenously at 3, 12-18 and 36-42 hours after birth. Standardized evaluation including cerebral sonography at day 1 and 7 and at 36 0/7 gestational weeks (or at discharge home if discharged before) will determine the presence or absence of complications. Cerebral volume and white matter volume will be assessed at 40 postmenstrual weeks with MRI (only if available).

Experienced examiners will assess developmental function at 24 months corrected age using the reliable and validly revised Bayley Scales II of Infant Development and determine the presence or absence of impairment of motor function (cerebral palsy) and neurosensory function (blindness or deafness).

CLINICAL SIGNIFICANCE At least 1 of every 100 liveborn infants is born very preterm. 90% of these infants survive but >50% have a delay in mental and physical development assessed at 24 months corrected age. More subtle problems affecting cognition, vision and hearing are common at the age of five years and have an impact on school performance and quality of life of the infants and their families. The aim of this trial is to examine whether a short, easily applicable and well tolerated pharmacological intervention can improve neurodevelopmental outcome.

  Eligibility

Ages Eligible for Study:   up to 3 Hours
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Infants born between 26 0/7 and 31 6/7 gestational weeks
  • Postnatal age less than 3 hours
  • Informed parental consent (preferably obtained before birth)

Exclusion Criteria:

  • Genetically defined syndrome
  • Severe congenital malformation adversely affecting life expectancy
  • Severe congenital malformation adversely affecting neurodevelopment
  • A priory palliative care
  • Intracranial haemorrhage grade 3 or more detected before dose 3 of Erythropoietin
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00413946

Locations
Switzerland
Kantonsspital
Aarau, Switzerland
Kantonsspital
Basel, Switzerland
Kantonsspital
Chur, Switzerland
Hopital universitaire
Geneva, Switzerland
University Hospital
Zurich, Switzerland, CH-8091
Sponsors and Collaborators
Swiss Neonatal Network
Swiss National Science Foundation
Investigators
Principal Investigator: Hans U Bucher, Prof University of Zurich
  More Information

Additional Information:
Publications:
Responsible Party: Bucher Hans Ulrich, full professor of Neonatology, Swiss Neonatal Network
ClinicalTrials.gov Identifier: NCT00413946     History of Changes
Other Study ID Numbers: 3200B0-108176, RoFAR ID 2127989593, 3200B0-108176
Study First Received: December 18, 2006
Last Updated: August 12, 2013
Health Authority: Switzerland: Swissmedic

Keywords provided by Swiss Neonatal Network:
Premature infant
developmental outcome

Additional relevant MeSH terms:
Leukomalacia, Periventricular
Cerebral Palsy
Hemorrhage
Intracranial Hemorrhages
Brain Damage, Chronic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Pathologic Processes
Cerebrovascular Disorders
Encephalomalacia
Vascular Diseases
Cardiovascular Diseases
Infant, Premature, Diseases
Infant, Newborn, Diseases
Epoetin Alfa
Hematinics
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 17, 2014