Erythropoietin, magnesium sulfate and hypothermia for hypoxic-ischemic encephalopathy
| ISRCTN | ISRCTN33604417 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN33604417 |
| Secondary identifying numbers | UMIN 00003267 |
- Submission date
- 10/09/2018
- Registration date
- 14/09/2018
- Last edited
- 05/04/2019
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Neonatal Diseases
Plain English summary of protocol
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
Contact information
Scientific
Department of Neonatology, Osaka City General Hospital
2-13-22 Miyakojima-hondori, Miyakojima-ku
Osaka
534-0021
Japan
| Phone | +81 (0)669291221 |
|---|---|
| h-ichiba@med.osaka-cu.ac.jp |
Study information
| Study design | Interventional non-randomised study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Non randomised study |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Scientific title | Erythropoietin, magnesium sulfate and hypothermia for hypoxic-ischemic encephalopathy |
| Study objectives | Erythropoietin (Epo) and magnesium sulfate in combination with hypothermia is safe and feasible in neonates with hypoxic-ischemic encephalopathy. |
| Ethics approval(s) | Institutional ethics committee of Osaka City General Hospital, 21/08/2013, ref: 1306022 |
| Health condition(s) or problem(s) studied | 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 |
| Pharmaceutical study type(s) | |
| Phase | Phase I |
| Drug / device / biological / vaccine name(s) | 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 study start date | 01/04/2013 |
| Completion date | 31/12/2017 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Neonate |
| Sex | Both |
| Target number of participants | 9 |
| Key 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 |
| Key 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 |
| Date of first enrolment | 07/02/2014 |
| Date of final enrolment | 04/06/2015 |
Locations
Countries of recruitment
- Japan
Study participating centre
Osaka
534-0021
Japan
Sponsor information
Hospital/treatment centre
2-13-22 Miyakojima-hondori, Miyakojima-ku
Osaka
534-0021
Japan
| Phone | +81 (0)669291221 |
|---|---|
| h-ichiba@med.osaka-cu.ac.jp | |
"ROR" |
https://ror.org/00v053551 |
Funders
Funder type
Research organisation
Government organisation / Local government
- Alternative name(s)
- 日本医療研究開発機構, The Japan Agency for Medical Research and Development, AMED
- Location
- Japan
Results and Publications
| Intention to publish date | 11/10/2018 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | Planned publication in a high-impact peer reviewed journal. |
| IPD sharing plan | 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). |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | results | 01/12/2019 | Yes | No |
Editorial Notes
05/04/2019: Publication reference added.
