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Premature InfantPhase 2NCT02550054

Erythropoietin in Premature Infants to Prevent Encephalopathy

A Phase 2 study testing Epo and Normal saline in people with Premature Infant, run by Children's Hospital of Fudan University at 1 site in China.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

The main goal of this trial is to investigate whether early administration of human erythropoietin (EPO) in preterm infants improves neurodevelopmental outcome at 18 months corrected age. This study is designed as randomized, double-masked, placebo controlled multicenter study involving at least 312 patients. Read more about this study

Who is it for?
Ages Up to 48 hours
Conditions the study is for
Premature Infant
What is being tested?
Epo and Normal saline
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
58 participants
Where
1 siteChina
Study dates
8 Sep 2015to 30 Dec 2016
Phase
Phase 2
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 Up to 48 hours
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • Birthweight less or equal 1500 grams
  • Less than 32 weeks gestation at birth
  • Less than 48 hours of life at time of enrollment
  • Written informed consent of parent or guardian

Who cannot join

  • Intrauterine Growth Retardation
  • Severe Congenital Anomalies adversely affecting life expectancy or neurodevelopment
  • Genetic Metabolic Diseases
  • Seizures within first 24 hours of life
  • Severe neutropenia (ANC < 500 cells/microL) within first 24 hours of life
  • Polycythemia (Hct > 65%) within first 24 hours of life
Show all 16Show fewer
  • Thrombocytopenia (platelets < 50K cells/microL) within first 24 hours of life
  • Hypertension (SBP > 100mmHg) without vasopressor support within first 24 hours of life
  • Microcephaly
  • Grade III-IV intracranial hemorrhage
  • Termination
  • Required by parent or guardian;
  • Polycythemia through blood transfusion can not be relieved
  • Oliguria（<0.5mL/kg/h for at least 24 hours）
  • Progression of azotemia
  • Pulmonary hypertension or Cardiac arrhythmia

Trial locations and contacts

1 site in 1 country.

China1 site

  • Children Hospital of Fudan University

    Shanghai, Shanghai Municipality, 201102

Other trials in China

About this study

Official title: Erythropoietin in Premature Infants to Prevent Encephalopathy: A Multi-Centre Randomized Blinded Controlled Study of the Efficacy of Erythropoietin in China

The main goal of this trial is to investigate whether early administration of human erythropoietin (EPO) in preterm infants improves neurodevelopmental outcome at 18 months corrected age. This study is designed as randomized, double-masked, placebo controlled multicenter study involving at least 312 patients.

Read the detailed description

EPO has been safely used for prevent preterm anemia and recent studies have shown the neuro-protective effect. Our hypothesis is that EPO could prevent preterm brain injury and reduce the rate of premature death and disability from encephalopathy. The aims of this study include: to investigate the safety and efficacy of EPO by using 1000u/kg higher than the dose of anemia treatment (250u/kg); to evaluate the effect of EPO on neurodevelopment in preterm infants; to detect biological and imaging indicators of EPO. Eligible premature infants will be enrolled in this double-blind, placebo-controlled randomized trial from the neonatal neurological intensive care unit (NNICU) at 7 Children's Hospital in 6 provinces of China. Subjects will be enrolled within the first 24 hours of life and randomly assigned to receive Epo or saline vehicle placebo. Standard NICU care will be provided to all subjects. Pharmacokinetic data, serial brain electrophysiologic and imaging exams, circulating inflammatory mediators, biomarkers and complications like polycythemia, neutropenia, thrombocytopenia, hypertension, sepsis, hemorrhage, seizure, necrotizing enterocolitis (NEC), persistent ductus arterious (PDA), apnea of prematurity, pulmonary haemorrhage, pulmonary hypertension, Prolonged blood coagulation time, retinopathy of prematurity (ROP), cardiac arrhythmia, major venous thrombosis, Renal failure treated with dialysis, pneumonia, pulmonary airleak and chronic lung disease will be collected at established time points during the study period. At 18 months corrected age, subjects will undergo a neurodevelopmental evaluation assessing for cerebral palsy, Bayley Scores of Mental Development Index (MDI) use.

Being tested
Epo, Normal saline
Medical subject headings
Premature Birth

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • EpoDrug

    Also called Epoietin Beta

    Epo is administered 1000 U/kg, iv in 48 hours after premature birth, and at 48 hours interval for 3 doses per week. After 6 doses, subcutaneously 400 U/Kg per injection and 3 doses per week until at corrected age of 34 weeks.

  • Normal salineDrug

    Also called N/S solution

    Normal saline is administered 5ml, iv at 3 to 6 hours after premature birth, and at 48 hours interval for 3 doses per week. After 6 doses, Subcutaneously 3 doses per week until at corrected age of 34 weeks.

Study groups in NCT02550054
Study groupRoleWhat they receive
ErythropoietinExperimentalEpo is administered 1000 U/kg, iv in 48 hours after premature birth, and at 48 hours interval for 3 doses per week. After 6 doses, Subcutaneously 3 doses per week until at corrected age of 34 weeks.
Receives: Drug: Epo
Normal salinePlacebo comparatorNormal saline is administered 5ml, iv at 3 to 6 hours after premature birth, and at 48 hours interval for 3 doses per week. After 6 doses, Subcutaneously 3 doses per week until at corrected age of 34 weeks.
Receives: Drug: Normal saline

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Neurodevelopment(Bayley Scores)

    To evaluate neurodevelopmental function via Bayley Scores of Infant Development Mental Development Index (BSID) and gain incidence of MDI<70(Severe) or MDI<85(Moderate).

    Measured: At corrected age of 18 months

  2. Neurological Evaluation(GMFM-88 Scores)

    To gain changes in standardized gross motor function using GMFM (Gross Motor Function Measure) as a standardized measurement tool for assessing Gross Motor Function consisting of sub-scales, lying \& rolling, sitting, crawling \& kneeling, standing, walking, running \& jumping (range: 0~100 , Higher value means better gross motor function).

    Measured: At corrected age of 18 months

Secondary outcomes (16)

  1. Brain Structural Alterations(MRI)

    To compare changes in brain as measured by MRI in Epo treatment and control groups at 9 months.

    Measured: At corrected age of 9 months

  2. Brain Structural Alterations(MRI)

    To compare changes in brain as measured by MRI in Epo treatment and control groups at 18 months.

    Measured: At corrected age of 18 months

  3. Intracranial Hemorrhage(MRI)

    To compare changes in brain as measured by MRI in Epo treatment and control groups at 9 months.

    Measured: At corrected age of 9 months

  4. Intracranial Hemorrhage(MRI)

    To compare changes in brain as measured by MRI in Epo treatment and control groups at 18 months.

    Measured: At corrected age of 18 months

  5. Brain Parenchyma Alterations(MRI)

    To compare changes in brain as measured by MRI in Epo treatment and control groups at 9 months.

    Measured: At corrected age of 9 months

  6. Brain Parenchyma Alterations(MRI)

    To compare changes in brain as measured by MRI in Epo treatment and control groups at 18 months.

    Measured: At corrected age of 18 months

  7. Somatosensory Evoked Potential

    To compare changes in brain electrophysiology by SSEP at 36 weeks.

    Measured: At corrected age of 9 months

  8. Somatosensory Evoked Potential

    To compare changes in brain electrophysiology by SSEP at 18 months.

    Measured: At corrected age of 18 months

  9. Visual Evoked Potential

    To compare changes in brain electrophysiology by VEP at 36 weeks.

    Measured: At corrected age of 9 months

  10. Visual Evoked Potential

    To compare changes in brain electrophysiology by VEP at 18 months.

    Measured: At corrected age of 18 months

  11. Brain Stem Auditory Evoked Potential

    To compare changes in brain electrophysiology by BAER at 36 weeks.

    Measured: At corrected age of 9 months

  12. Brain Stem Auditory Evoked Potential

    To compare changes in brain electrophysiology by BAER at 18 months.

    Measured: At corrected age of 18 months

  13. Incidence of complication

    To gain the incidence of Polycythemia, neutropenia, thrombocytopenia, hypertension, sepsis, intraventricular hemorrhage(IVH), periventricular leukomalacia(PVL), seizure, necrotizing enterocolitis (NEC), persistent ductus arterious (PDA), apnea of prematurity, pulmonary haemorrhage, pulmonary hypertension, Prolonged blood coagulation time, retinopathy of prematurity(ROP), cardiac arrhythmia, major venous thrombosis, Renal failure treated with dialysis, pneumonia, pulmonary airleak and chronic lung disease.

    Measured: During treament period (in 34 weeks)

  14. SDF-1 in Serum

    Biomarkers for Oxidative Stress, Inflammation and immune response as a measure of efficacy of erythropoietin for hypoxic ischemic encephalopathy.

    Measured: At 34 weeks

  15. TNF-alpha in Serum

    Biomarkers for Oxidative Stress, Inflammation and immune response as a measure of efficacy of erythropoietin for hypoxic ischemic encephalopathy.

    Measured: At 34 weeks

  16. IL-1 in Serum

    Biomarkers for Oxidative Stress, Inflammation and immune response as a measure of efficacy of erythropoietin for hypoxic ischemic encephalopathy.

    Measured: At 34 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Sep 2015 (estimated)
  2. Study start8 Sep 2015
  3. Primary completion30 Dec 2016
  4. Study completion30 Dec 2016

Why it stopped: The study was concluded as planned upon reaching its predetermined endpoint, which included the completion of data collection and achievement of the necessary sample size for statistical significance.

Resources

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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Outcomes assessor
Enrolment
58 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02550054
Sponsor's protocol ID
CHFudanU_NNICU4
Status last verified
Dec 2023
First submitted
4 Sep 2015
Last updated
29 Dec 2023
Results posted
No
Data monitoring committee
Yes

Publications

  • Leuchter RH, Gui L, Poncet A, Hagmann C, Lodygensky GA, Martin E, Koller B, Darque A, Bucher HU, Huppi PS. Association between early administration of high-dose erythropoietin in preterm infants and brain MRI abnormality at term-equivalent age. JAMA. 2014 Aug 27;312(8):817-24. doi: 10.1001/jama.2014.9645.

    PubMed 25157725

  • Dame C, Langer J, Koller BM, Fauchere JC, Bucher HU. Urinary erythropoietin concentrations after early short-term infusion of high-dose recombinant epo for neuroprotection in preterm neonates. Neonatology. 2012;102(3):172-7. doi: 10.1159/000339283. Epub 2012 Jul 4.

    PubMed 22776958

  • Kuki I, Kawawaki H, Horino A, Inoue T, Nukui M, Okazaki S, Tomiwa K, Amo K, Togawa M, Shiomi M. [A clinical study on high-dose erythropoietin therapy for acute encephalopathy or encephalitis]. No To Hattatsu. 2015 Jan;47(1):32-6. Japanese.

    PubMed 25803909

  • Traudt CM, McPherson RJ, Bauer LA, Richards TL, Burbacher TM, McAdams RM, Juul SE. Concurrent erythropoietin and hypothermia treatment improve outcomes in a term nonhuman primate model of perinatal asphyxia. Dev Neurosci. 2013;35(6):491-503. doi: 10.1159/000355460. Epub 2013 Nov 1.

    PubMed 24192275

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Epo and Normal saline in people with Premature Infant, run by Children's Hospital of Fudan University at 1 site in China.

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 16 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: stopped early, as of the sponsor's last update on 29 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: The study was concluded as planned upon reaching its predetermined endpoint, which included the completion of data collection and achievement of the necessary sample size for statistical significance.). 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?

Neurodevelopment(Bayley Scores) (time frame: At corrected age of 18 months). The study lists 2 primary outcomes in all. 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 NCT02550054, which also lists 4 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 29 Dec 2023.

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