Erythropoietin for the Repair of Cerebral Injury in Very Preterm Infants

Intraventricular Hemorrhage of Prematurity Clinical Trial

— EpoRepair  

Official title:

Erythropoietin for the Repair of Cerebral Injury in Very Preterm Infants - a Randomized, Double-blind, Placebo-controlled, Prospective, and Multicenter Clinical Study

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02076373
• Other study ID #: EpoRepair
• Secondary ID: 2013DR3204
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: March 2014
• Est. completion date: March 2024

Study information

• Verified date: November 2018
• Source: University of Zurich
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 120
• Est. completion date: March 2024
• Est. primary completion date: December 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 23 Weeks to 31 Weeks

Eligibility

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

Related Conditions & MeSH terms

• Brain Injuries
• Cerebral Hemorrhage
• Hemorrhage
• Intraventricular Hemorrhage of Prematurity

Intervention

Drug:
• recombinant human Erythropoietin
i.v. administration
• Placebo
i.v. administration

Locations

Country	Name	City	State
Austria	Medical University of Vienna	Vienna
Switzerland	Kantonsspital Aarau	Aarau
Switzerland	University Children's Hospital Basel (UKBB)	Basel
Switzerland	University Hospital Bern	Bern
Switzerland	Kantonsspital Graubünden	Chur
Switzerland	Centre Hospitalier Universitaire Vaudois (CHUV)	Lausanne
Switzerland	Ostschweizer Kinderspital	St. Gallen
Switzerland	University Hospital Zurich	Zurich

Sponsors (2)

Lead Sponsor	Collaborator
University of Zurich	Swiss National Science Foundation

Countries where clinical trial is conducted

Austria,  Switzerland, 

References & Publications (1)

Rüegger CM, Hagmann CF, Bührer 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Course of intracerebral bleeding	Course of intracerebral bleeding from onset until term equivalent age with additional visits at 28 days of life and 36 weeks postmenstrual age.; No remaining lesions as recorded by cranial ultrasound; Persisting posthemorrhagic hydrocephalus without any drainage; Persisting posthemorrhagic hydrocephalus with repetitive but transient csf-drainage; Posthemorrhagic hydrocephalus with permanent csf-drainage; Convulsions and other abnormalities or medications related to intracerebral bleeding	Infants will be followed for the duration of hospital stay, an expected average of 14 weeks
Primary	Neurodevelopmental outcome	With 5 years of age, composite intelligence quotient to be assessed by standardized IQ tests.	5 years
Secondary	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.	40 weeks postmenstrual age
Secondary	Safety	Analysis will be performed to get insight about the distributions of adverse events and other safety relevant outcomes between groups.	Infants will be followed for the duration of hospital stay, an expected average of 14 weeks
Secondary	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.	2 years
Secondary	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.	Infants will be followed for the duration of hospital stay, an expected average of 14 weeks
Secondary	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.	5 years

External Links

•   EpoRepair trial homepage