Intraventricular Hemorrhage of PrematurityPhase 3EpoRepairNCT02076373
Erythropoietin for the Repair of Cerebral Injury in Very Preterm Infants
A Phase 3 study testing recombinant human Erythropoietin in people with Intraventricular Hemorrhage of Prematurity, run by University of Zurich at 8 sites in 2 countries.
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. Read more about this study
- Who is it for?
- Ages 23 to 31 weeks
- Conditions the study is for
- Intraventricular Hemorrhage of Prematurity
- What is being tested?
- recombinant human Erythropoietin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 120 participants
- Where
- 8 sitesin 2 countries
- Study dates
- Mar 2014to Mar 2024
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 23 to 31 weeks
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Infants with less than 32 weeks of gestation and/or less than 1500 g weight at birth
- Intraventricular hemorrhage and/or hemorrhagic parenchymal infarction
- Less than 8 days of life
- Informed written parental consent
Who cannot join
- Genetically defined syndrome
- Severe congenital malformation adversely affecting life expectancy and/or neurodevelopment
- A priory palliative care
- Unlikely to participate at 5-year follow-up examination
Trial locations and contacts
8 sites in 2 countries.
8 sites in 2 countries
Switzerland7 sites
Kantonsspital Aarau
Aarau, 5001
University Children's Hospital Basel (UKBB)
Basel, 4031
University Hospital Bern
Bern, 3010
Kantonsspital Graubünden
Chur, 7000
Centre Hospitalier Universitaire Vaudois (CHUV)
Lausanne, 1011
Ostschweizer Kinderspital
Sankt Gallen, 9006
University Hospital Zurich
Zurich, 8091
About this study
Official title: Erythropoietin for the Repair of Cerebral Injury in Very Preterm Infants - a Randomized, Double-blind, Placebo-controlled, Prospective, and Multicenter Clinical Study
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.
Read the 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.
- Being tested
- recombinant human Erythropoietin, Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
recombinant human ErythropoietinDrug
Also called Epoetin beta
i.v. administration
PlaceboDrug
Also called normal saline
i.v. administration
| Study group | Role | What they receive |
|---|---|---|
| recombinant human Erythropoietin (Epo) | Experimental | 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. Receives: Drug: recombinant human Erythropoietin |
| Control | Placebo comparator | 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Neurodevelopmental outcome
With 5 years of age, composite intelligence quotient to be assessed by standardized IQ tests.
Measured: 5 years
Secondary outcomes (5)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Mar 2014 (estimated)
- Study startMar 2014
- Primary completionDec 2023 (estimated)
- Study completionMar 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Intraventricular Hemorrhage of PrematurityStudies of the same condition, open and under way.
- More trials run by University of ZurichThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 120 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Zurich
- Sponsor type
- University, hospital or other
- Collaborators
- Swiss National Science Foundation
- Responsible party
- Sponsor
- Investigators
- Sven Wellmann, MD, Principal investigator, University of ZurichHans Ulrich Bucher, MD, PhD, Study chair, University of Zurich
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02076373
- Sponsor's protocol ID
- EpoRepair
- Other IDs
- 2013DR3204
- Acronym
- EpoRepair
- Status last verified
- Nov 2018
- First submitted
- 25 Feb 2014
- Last updated
- 23 Nov 2018
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Publications
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.
PubMed 26278911Wellmann 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.
PubMed 36459138
Study at a glance
From the registry record, last updated by the sponsor on 23 Nov 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Erythropoietin for the Repair of Cerebral Injury in Very Preterm Infants - a Randomized, Double-blind, Placebo-controlled, Prospective, and Multicenter Clinical Study
- ClinicalTrials.gov ID
- NCT02076373
- Acronym / sponsor ID
- EpoRepair / EpoRepair
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 120 participants (actual)
- Lead sponsor
- University of ZurichUniversity, hospital or other
- Collaborators
- Swiss National Science Foundation
- Study start
- Mar 2014
- Primary completion
- Dec 2023 (estimated)
- Study completion
- Mar 2024 (estimated)
- First posted
- 3 Mar 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| recombinant human Erythropoietin (Epo) | Experimental | Drug: recombinant human ErythropoietinEpo 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. |
| Control | Placebo comparator | Drug: PlaceboPlacebo 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. |
Who may qualify
- Ages
- 23 to 31 weeks
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- Infants with less than 32 weeks of gestation and/or less than 1500 g weight at birth
- Intraventricular hemorrhage and/or hemorrhagic parenchymal infarction
- Less than 8 days of life
- Informed written parental consent
Key exclusion criteria (4 listed)
- Genetically defined syndrome
- Severe congenital malformation adversely affecting life expectancy and/or neurodevelopment
- A priory palliative care
- Unlikely to participate at 5-year follow-up examination
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| recombinant human ErythropoietinAlso: Epoetin betai.v. administration | Drug | recombinant human Erythropoietin (Epo) |
| PlaceboAlso: normal salinei.v. administration | Drug | Control |
Primary outcome
Neurodevelopmental outcome
Time frame: 5 years
With 5 years of age, composite intelligence quotient to be assessed by standardized IQ tests.
5 secondary outcomes
Biomarker cranial MRI
Time frame: 40 weeks postmenstrual age
Safety
Time frame: Infants will be followed for the duration of hospital stay, an expected average of 14 weeks
Neurodevelopmental outcome
Time frame: 2 years
Biomarker serial cranial ultrasound
Time frame: Infants will be followed for the duration of hospital stay, an expected average of 14 weeks
Overall developmental outcome
Time frame: 5 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Nov 2018.
- Background: PubMed 26278911Ruegger 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.
- Derived from this study: PubMed 36459138Wellmann 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.
- EpoRepair trial homepageLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided
Related trials for Intraventricular Hemorrhage of Prematurity
Recruiting
Optimization of Saturation Targets And Resuscitation Trial (OptiSTART)
Premature Infants, Bronchopulmonary Dysplasia
RecruitingObservational study
The Correlation Between Red Cell Transfusion and Complications of Prematurity
Retinopathy of Prematurity (ROP), Bronchopulmonary Dysplasia (BPD)
Enrolling by invitationObservational study
Intelligent Physiological Monitoring to Predict Preterm Brain Injury
Cerebral Palsy (CP), Intraventricular Hemorrhage Neonatal
Not yet recruiting
Intranasal Fresh Mother's Own Milk to Prevent Intraventricular Hemorrhage in Extremely Preterm Infants
Intraventricular Hemorrhage, Premature Birth
Active, not recruitingPhase 2
A Clinical Efficacy and Safety Study of OHB-607 in Preventing Bronchopulmonary Dysplasia in Extremely Premature Infants
Bronchopulmonary Dysplasia, Chronic Lung Disease of Prematurity
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sven Wellmann, MD principal investigator
University of Zurich
Hans Ulrich Bucher, MD, PhD study chair
University of Zurich
8 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing recombinant human Erythropoietin in people with Intraventricular Hemorrhage of Prematurity, run by University of Zurich at 8 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 23 Nov 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in Switzerland, Austria. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Neurodevelopmental outcome (time frame: 5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02076373, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Nov 2018.