Erythropoietin for the Repair of Cerebral Injury in Very Preterm Infants

NCT ID: NCT02076373

Last Updated: 2018-11-23

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-03-31
• Study Completion Date: 2024-03-31

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.

Conditions

Intraventricular Hemorrhage of Prematurity

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

recombinant human Erythropoietin (Epo)

Epo 2000 U in normal saline per ml/kg of body weight 5 times intravenously, total dosage 10000 U per 5ml/kg.

In detail: For loading 3 times beginning at day 5 of life (± 2 days), followed at 24 hours and 48 hours later. For maintenance 2 times, at day 10 and day 17 after the first study medication.

Group Type: EXPERIMENTAL

recombinant human Erythropoietin

Intervention Type: DRUG

i.v. administration

Control

Placebo 1 ml normal saline/kg of body weight 5 times intravenously, total dosage 5 ml/kg.

In detail: For loading 3 times beginning at day 5 of life (± 2 days), followed at 24 hours and 48 hours later. For maintenance 2 times, at day 10 and day 17 after the first study medication.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

i.v. administration

Interventions

recombinant human Erythropoietin

i.v. administration

Intervention Type: DRUG

Placebo

i.v. administration

Intervention Type: DRUG

Other Intervention Names

Epoetin beta; normal saline

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

• Minimum Eligible Age: 23 Weeks
• Maximum Eligible Age: 31 Weeks
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Swiss National Science Foundation

OTHER

Sponsor Role: collaborator

University of Zurich

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sven Wellmann, MD

Role: PRINCIPAL_INVESTIGATOR

University of Zurich

Hans Ulrich Bucher, MD, PhD

Role: STUDY_CHAIR

University of Zurich

Locations

Medical University of Vienna

Vienna, , Austria

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

Sankt Gallen, , Switzerland

University Hospital Zurich

Zurich, , Switzerland

Countries

Austria; Switzerland

References

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.

Reference Type: BACKGROUND

PMID: 26278911 (View on PubMed)

Wellmann S, Hagmann CF, von Felten S, Held L, Klebermass-Schrehof K, Truttmann AC, Knopfli C, Fauchere JC, Buhrer C, Bucher HU, Ruegger CM; Erythropoietin for the Repair of Cerebral Injury in Very Preterm Infants (EpoRepair) Investigators. Safety and Short-term Outcomes of High-Dose Erythropoietin in Preterm Infants With Intraventricular Hemorrhage: The EpoRepair Randomized Clinical Trial. JAMA Netw Open. 2022 Dec 1;5(12):e2244744. doi: 10.1001/jamanetworkopen.2022.44744.

Reference Type: DERIVED

PMID: 36459138 (View on PubMed)

Related Links

http://www.eporepair.ch

EpoRepair trial homepage

Other Identifiers

2013DR3204

Identifier Type: OTHER

Identifier Source: secondary_id

EpoRepair

Identifier Type: -

Identifier Source: org_study_id