Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Does Erythropoietin Improve Outcome in Very Preterm Infants?

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00413946
Recruitment Status : Completed
First Posted : December 20, 2006
Last Update Posted : October 30, 2018
Sponsor:
Collaborator:
Swiss National Science Foundation
Information provided by (Responsible Party):
Bucher Hans Ulrich, Swiss Neonatal Network

Tracking Information
First Submitted Date  ICMJE December 18, 2006
First Posted Date  ICMJE December 20, 2006
Last Update Posted Date October 30, 2018
Study Start Date  ICMJE January 2006
Actual Primary Completion Date December 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 9, 2011)
Mental developmental index (Bayley II) and motor, visual and hearing impairment [ Time Frame: at age of 24 months corrected for prematurity. ]
Original Primary Outcome Measures  ICMJE
 (submitted: December 19, 2006)
  • incidence and severity of intracranial haemorrhage and white matter disease
  • assessed with ultrasound and MRI, mental developmental index (Bayley II)
  • and motor, visual and hearing impairment at 24 months corrected for prematurity.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 19, 2014)
  • MRI at term equivalent [ Time Frame: 40 postmenstrual weeks ]
    White matter injury score grey matter injury score brain maturation
  • cerebral palsy. [ Time Frame: First 24 months of life (corrected for prematurity) ]
  • Cognitive development and cerebral palsy [ Time Frame: 5 years ]
    Kaufmann ABC II, standardized neurological, visual and hearing examination, questionnaire about health status and behavior. Classification of impairments, disabilities and handicaps.
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Does Erythropoietin Improve Outcome in Very Preterm Infants?
Official Title  ICMJE Neuroprotective Effect of High Dose Erythropoietin in Very Preterm Infants
Brief Summary

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 multicenter study involving at least 420 patients.

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 26 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.

Biomarkers of encephalopathy of prematurity assessed on magnetic resonance imaging (MRI) at term equivalent age.

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 multicenter 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 live born 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Condition  ICMJE
  • Intracranial Hemorrhage
  • Periventricular Leukomalacia
  • Cerebral Palsy
  • Developmental Psychomotor Disorders
Intervention  ICMJE
  • Drug: Recombinant human Erythropoietin
    3 doses 3000 units (1 ml) of recombinant human erythropoietin per kg body weight
  • Drug: saline
    three doses of 1.0 ml saline per body weight
    Other Name: NaCl 0.9%
Study Arms  ICMJE
  • Experimental: Erythropoietin
    Three doses of rErythropoietin (3000 U/kg body weight) intravenously at 3, 12-18 and 36-42 hours after birth.
    Intervention: Drug: Recombinant human Erythropoietin
  • Placebo Comparator: saline
    Three doses of placebo (0.9% saline 1 ml/kg body weight) intravenously at 3, 12-18 and 36-42 hours after birth
    Intervention: Drug: saline
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 19, 2006)
420
Original Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE December 2012
Actual Primary Completion Date December 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 3 Hours   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Switzerland
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00413946
Other Study ID Numbers  ICMJE 3200B0-108176
RoFAR ID 2127989593 ( Other Grant/Funding Number: 3200B0-108176 )
3200B0-108176 ( Other Grant/Funding Number: SNF 3200B0-108176 )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Bucher Hans Ulrich, Swiss Neonatal Network
Study Sponsor  ICMJE Swiss Neonatal Network
Collaborators  ICMJE Swiss National Science Foundation
Investigators  ICMJE
Principal Investigator: Hans U Bucher, Prof University of Zurich
PRS Account Swiss Neonatal Network
Verification Date October 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP