Erythropoietin for the Repair of Cerebral Injury in Very Preterm Infants

Phase 3UnknownNCT02076373

University of Zurich120 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

120

Conditions

Intraventricular Hemorrhage of Prematurity

Interventions

recombinant human ErythropoietinDRUG

i.v. administration

PlaceboDRUG

i.v. administration

Eligibility

Sex: ALLMin age: 23 WeeksMax age: 31 Weeks

Medical Language ↔ Plain English

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

Locations (8)

Medical University of Vienna

Vienna, Austria

Kantonsspital Aarau

Aarau, Switzerland

University Children's Hospital Basel (UKBB)

Basel, Switzerland

University Hospital Bern

Bern, Switzerland

Outcomes

Primary Outcomes

Neurodevelopmental outcome

With 5 years of age, composite intelligence quotient to be assessed by standardized IQ tests.

Time frame: 5 years

Secondary Outcomes

Biomarker cranial MRI

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.

Time frame: 40 weeks postmenstrual age

Safety

Analysis will be performed to get insight about the distributions of adverse events and other safety relevant outcomes between groups.

Time frame: Infants will be followed for the duration of hospital stay, an expected average of 14 weeks

Neurodevelopmental outcome

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.

Time frame: 2 years

Biomarker serial cranial ultrasound

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.

Time frame: Infants will be followed for the duration of hospital stay, an expected average of 14 weeks

Overall developmental outcome

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.

Data from ClinicalTrials.gov

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