Intraventricular Hemorrhage of Prematurity
Conditions
Brief summary
The purpose of this randomized and placebo-controlled EpoRepair trial is to evaluate the effect of intravenously administered recombinant human erythropoietin (Epo) as compared to placebo in preterm infants with brain damage on neurological development until five years od age.
Detailed description
Worldwide, 1% of all infants are born very preterm with less than 32 weeks of gestation, which is more than 2 months before expected date of delivery. If these smallest infants suffer in addition to prematurity a second hit, such as intraventricular hemorrhage or parenchymal infarction, they are at high risk for learning disabilities, mental retardation, and cerebral palsy in later life. Intraventricular hemorrhage and parenchymal infarction occur in about 12% of very preterm infants, mostly in the very smallest and within the first few days after birth, and can be recorded by cranial ultrasound. Except for shunt insertion to divert cerebrospinal fluid in infants with posthemorrhagic hydrocephalus and possibly the removal of blood clots, there is no treatment for established intracerebral bleeding, and no medical therapies exist to ameliorate the neurodevelopmental sequelae. Apart from stimulating production of red blood cells in the bone marrow, recombinant human erythropoietin (Epo) has been shown to exert neuroprotective action in a variety of animal models and in clinical studies. Epo administration has been found to be beneficial and safe in randomized controlled trials (RCT) involving adult and infant patients. Observational data suggest that Epo administered to very preterm infants in order to prevent from anemia improves long-term cognitive outcomes until school-age especially in those infants who had suffered intracerebral bleeding. These data, however, are observational and therefore do not allow for any firm conclusions or recommendations. The hypothesis generated by these data calls for confirmation or refutation by an RCT designed to address this question.
Interventions
DRUGrecombinant human Erythropoietin
i.v. administration
DRUGPlacebo
i.v. administration
Sponsors
Swiss National Science Foundation
University of Zurich
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
23 Weeks to 31 Weeks
Healthy volunteers
No
Inclusion criteria
1. Infants with less than 32 weeks of gestation and/or less than 1500 g weight at birth 2. Intraventricular hemorrhage and/or hemorrhagic parenchymal infarction 3. Less than 8 days of life 4. Informed written parental consent
Exclusion criteria
1. Genetically defined syndrome 2. Severe congenital malformation adversely affecting life expectancy and/or neurodevelopment 3. A priory palliative care 4. Unlikely to participate at 5-year follow-up examination
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Neurodevelopmental outcome | 5 years | With 5 years of age, composite intelligence quotient to be assessed by standardized IQ tests. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Biomarker cranial MRI | 40 weeks postmenstrual age | Brain injury score assessed on cranial MRI, including brain maturation score and white matter and gray matter injury scores, as biomarker for long-term neurodevelopmental outcome. |
| Safety | Infants will be followed for the duration of hospital stay, an expected average of 14 weeks | Analysis will be performed to get insight about the distributions of adverse events and other safety relevant outcomes between groups. |
| Biomarker serial cranial ultrasound | Infants will be followed for the duration of hospital stay, an expected average of 14 weeks | Cranial ultrasound is a useful point of care method to detect, confirm and monitor brain damage including intracerebral bleeding. It is part of clinical routine for the duration of hospital stay. |
| Overall developmental outcome | 5 years | Neurological and formal psychological examination. Normal Overall developmental outcome is classified as normal if IQ \>84 and without one or more of the following: motor impairment, cognitive impairment, behavior problems, poor general health, severe hearing loss, or bilateral blindness. |
| Neurodevelopmental outcome | 2 years | Bayley Scales of Infant Development (BSID-III) and the presence or absence of impairment of motor function (cerebral palsy) and neurosensory function (blindness or deafness) will be assessed with 18 to 24 months. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Course of intracerebral bleeding | Infants will be followed for the duration of hospital stay, an expected average of 14 weeks | Course of intracerebral bleeding from onset until term equivalent age with additional visits at 28 days of life and 36 weeks postmenstrual age. 1. No remaining lesions as recorded by cranial ultrasound 2. Persisting posthemorrhagic hydrocephalus without any drainage 3. Persisting posthemorrhagic hydrocephalus with repetitive but transient csf-drainage 4. Posthemorrhagic hydrocephalus with permanent csf-drainage 5. Convulsions and other abnormalities or medications related to intracerebral bleeding |
Countries
Austria, Switzerland
Outcome results
None listed