Condition category
Neonatal Diseases
Date applied
10/09/2018
Date assigned
14/09/2018
Last edited
14/09/2018
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
Hypoxic Ischemic Encephalopathy (HIE) is a type of brain damage that occurs when a newborn’s brain doesn't receive enough oxygen and blood. It occurs in 1 to 3% of normal births. Nearly 20% of affected infants die during the postnatal period (after birth), while 25% develop central nervous system complications. Therapeutic hypothermia (reduction of body temperature) in newborns with HIE has been tested in six studies and has shown improvements in outcome. However, hypothermia was not always effective and resulted in death or moderate to severe disabilities in more than 40% of the patients. The addition of other strategies may improve the outcome, but it is not known which treatment is most effective in combination or whether these treatments are safe. Both erythropoietin (Epo) and magnesium sulfate are known to improve the outcome of HIE. The safety or effectiveness of Epo and magnesium sulfate in combination with hypothermia has not been studied to date. The aim of this study is to assess the safety and feasibility of the combination in newborns with HIE.

Who can participate?
Newborns with HIE admitted to the Osaka City General Hospital Neonatal Intensive Care Unit (NICU)

What does the study involve?
A combination treatment with Epo, magnesium sulfate and hypothermia is started within 6 hours of birth. Vital signs and side effects are recorded during the treatment. Short-term and long-term developmental outcomes are also assessed.

What are the possible benefits and risks of participating?
The benefit of participating is to receive the new treatment. The risk of participating is the rare possibility to have an unexpected side effect.

Where is the study run from?
Osaka City General Hospital (Japan)

When is the study starting and how long is it expected to run for?
April 2013 to December 2017

Who is funding the study?
Japan Agency for Medical Research and Development (Japan)

Who is the main contact?
Dr Hiroyuki Ichiba
h-ichiba@med.osaka-cu.ac.jp

Trial website

Contact information

Type

Scientific

Primary contact

Dr Hiroyuki Ichiba

ORCID ID

Contact details

Department of Neonatology
Osaka City General Hospital
2-13-22 Miyakojima-hondori
Miyakojima-ku
Osaka
534-0021
Japan
+81 (0)669291221
h-ichiba@med.osaka-cu.ac.jp

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

UMIN 00003267

Study information

Scientific title

Erythropoietin, magnesium sulfate and hypothermia for hypoxic-ischemic encephalopathy

Acronym

Study hypothesis

Erythropoietin (Epo) and magnesium sulfate in combination with hypothermia is safe and feasible in neonates with hypoxic-ischemic encephalopathy.

Ethics approval

Institutional ethics committee of Osaka City General Hospital, 21/08/2013, ref: 1306022

Study design

Interventional non-randomised study

Primary study design

Interventional

Secondary study design

Non randomised study

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Condition

Neonatal hypoxic-ischemic encephalopathy

Intervention

A combination therapy with erythropoietin (300 mg/kg every other day for 2 weeks), magnesium sulfate (250 mg/kg for 3 days) and hypothermia was started within 6 hours of birth in neonates who met the institutional criteria for hypothermia therapy. All patients received continuous infusion of dopamine. Vital signs and adverse events were recorded during the therapy. Short-term and long-term developmental outcomes were also evaluated.

Intervention type

Drug

Phase

Phase I

Drug names

Erythropoietin, magnesium sulfate

Primary outcome measure

Mortality and morbidity in neonatal period, measured by clinical records regarding in-hospital death, establishment of oral feeding, establishment of spontaneous respiration and brain MRI findings at 1 month of age

Secondary outcome measures

Neurodevelopmental outcome measured using the Kyoto Scale of Psychological Development (KSPD) at 18 months of age

Overall trial start date

01/04/2013

Overall trial end date

31/12/2017

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

Neonates admitted to the Osaka City General Hospital Neonatal Intensive Care Unit (NICU) and diagnosed with HIE, meeting institutional criteria for therapeutic hypothermia

Participant type

Patient

Age group

Neonate

Gender

Both

Target number of participants

9

Participant exclusion criteria

1. Infants older than 6 hours of birth at the time of initiation of hypothermia therapy
2. Infants with major congenital abnormalities
3. Infants with severe growth restriction with birth weight less than 1800 g
4. Infants who were considered critically ill and unlikely to benefit from neonatal intensive care by the attending neonatologist

Recruitment start date

07/02/2014

Recruitment end date

04/06/2015

Locations

Countries of recruitment

Japan

Trial participating centre

Osaka City General Hospital
2-13-22 Miyakojima-hondori, Miyakojima-ku
Osaka
534-0021
Japan

Sponsor information

Organisation

Osaka City General Hospital

Sponsor details

2-13-22 Miyakojima-hondori
Miyakojima-ku
Osaka
534-0021
Japan
+81 (0)669291221
h-ichiba@med.osaka-cu.ac.jp

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Research organisation

Funder name

Japan Agency for Medical Research and Development

Alternative name(s)

AMED

Funding Body Type

private sector organisation

Funding Body Subtype

other non-profit

Location

Japan

Results and Publications

Publication and dissemination plan

Planned publication in a high-impact peer reviewed journal.

IPD sharing statement
The datasets generated during and/or analysed during the current study are/will be available upon request from Dr Hiroyuki Ichiba (h-ichiba@med.osaka-cu.ac.jp).

Intention to publish date

11/10/2018

Participant level data

Available on request

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes