Clinical trial NCT02076373: Erythropoietin for the Repair of Cerebral Injury in Very Preterm Infants
Official title: Erythropoietin for the Repair of Cerebral Injury in Very Preterm Infants - a Randomized, Double-blind, Placebo-controlled, Prospective, and Multicenter Clinical Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Intraventricular Hemorrhage of Prematurity
Lead sponsor: University of Zurich
Sponsor class: OTHER
Collaborators: name: Swiss National Science Foundation
First posted: 2014-03-03
Enrollment: 120
Sex: ALL
Minimum age (years): 23
Maximum age (years): 31
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Neurodevelopmental outcome
timeFrame: 5 years
Secondary outcomes:
measure: Biomarker cranial MRI
timeFrame: 40 weeks postmenstrual age
measure: Safety
timeFrame: Infants will be followed for the duration of hospital stay, an expected average of 14 weeks
measure: Neurodevelopmental outcome
timeFrame: 2 years
measure: Biomarker serial cranial ultrasound
timeFrame: Infants will be followed for the duration of hospital stay, an expected average of 14 weeks
measure: Overall developmental outcome
timeFrame: 5 years
Other outcomes:
measure: Course of intracerebral bleeding
timeFrame: Infants will be followed for the duration of hospital stay, an expected average of 14 weeks
Locations:
city: Vienna
country: Austria
facility: Medical University of Vienna
city: Aarau
country: Switzerland
facility: Kantonsspital Aarau
city: Basel
country: Switzerland
facility: University Children's Hospital Basel (UKBB)
city: Bern
country: Switzerland
facility: University Hospital Bern
city: Chur
country: Switzerland
facility: Kantonsspital Graubünden
city: Lausanne
country: Switzerland
facility: Centre Hospitalier Universitaire Vaudois (CHUV)
city: St. Gallen
country: Switzerland
facility: Ostschweizer Kinderspital
city: Zurich
country: Switzerland
facility: University Hospital Zurich
Study officials:
affiliation: University of Zurich
name: Sven Wellmann, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Zurich
name: Hans Ulrich Bucher, MD, PhD
role: STUDY_CHAIR
References:
citation: Ruegger CM, Hagmann CF, Buhrer C, Held L, Bucher HU, Wellmann S; EpoRepair Investigators. Erythropoietin for the Repair of Cerebral Injury in Very Preterm Infants (EpoRepair). Neonatology. 2015;108(3):198-204. doi: 10.1159/000437248. Epub 2015 Aug 8.