MedDataX Logo

Erythropoietin in Management of Neonatal Hypoxic Ischemic Encephalopathy

NCT ID: NCT03163589

Last Updated: 2017-05-31

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

UNKNOWN

Clinical Phase

PHASE3

Total Enrollment

40 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-12-01

Study Completion Date

2020-06-01

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

Perinatal hypoxic-ischaemic encephalopathy occurs in one to three infants per 1000 term births, and up to 12 000 infants are affected each year in the united state of America. Hypoxic ischemic encephalopathy is not preventable in most cases, and therapies are limited. Hypothermia improves outcomes and is the current standard of care. Yet clinical trials suggest that 44% to 53% of infants who receive hypothermia will die or suffer moderate to severe neurological disability. Therefore, novel neuroprotective therapies are urgently needed to further reduce the rate and severity of neurodevelopmental disabilities resulting from hypoxic ischemic encephalopathy.

Erythropoietin is a novel neuroprotective agent, with remarkable neuroprotective and neuroregenerative effects in animals. Rodent and primate models of neonatal brain injury support the safety and efficacy of multiple erythropoietin doses for improving histological and functional outcomes after hypoxia-ischaemia.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

The cellular mechanisms by which erythropoietin exert neuroprotection are complex and not completely understood. In the acute period after hypoxia ischaemia, erythropoietin signaling in the brain induces several neuroprotective mechanisms. In addition to its anti-apoptotic and anti-inflammatory properties, erythropoietin also increases antioxidant activities and reduces excitotoxic cell injury.

In addition to its acute effects, erythropoietin stimulates growth factor release, enhances neurogenesis and angiogenesis, and promotes long-term repair and plasticity. Thus, erythropoietin provides neuroprotective and trophic effects that last well beyond the acute period of injury erythropoietin .enhances neurogenesis and directs multipotent neural stem cells to differentiate toward a neuronal cell fate.

In a clinical trial performed in China, Zhu et al. studied 167 neonates with of hypoxic ischemic encephalopathy that were randomized to receive erythropoietin (300-500U/kg) or placebo every second day for 2 weeks. The first dose of erythropoietin was given within 48 hours of delivery. Compared with placebo-treated infants, infants that received erythropoietin were less likely to die or have moderate to severe disability at 18 months of age (44% vs 25%, p=0.02).

Similarly, Elmahdy et al. studied 30 infants with hypoxic ischemic encephalopathy who were randomized to receive five daily doses of 2500 units/kg erythropoietin, or placebo, with the first dose given within 24 hours of delivery. The erythropoietin-treated infants demonstrated improved electroencephalography backgrounds, reduced biomarkers of oxidative stress after 2 weeks, and improved neurodevelopment at 6 months of age compared with placebo treated infants.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Hypoxic-Ischemic Encephalopathy

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

study group

Within 4 to 6 hours after birth all cases with moderate to severe hypoxic ischemic encephalopathy will be enrolled in therapeutic hypothermia using total body cooling and temperature and Receive erythropoietin (1000 U/kg intravenously) on days 1, 2, 3, 5 ,7 and 9 (six doses,first two doses will be daily from the first day and last 4 doses will be every 2 days)

Group Type EXPERIMENTAL

Erythropoietin

Intervention Type DRUG

injection

control group

Within 4 to 6 hours after birth cases with moderate to severe hypoxic ischemic encephalopathy enrolled in therapeutic hypothermia using total body cooling and temperature and Receive normal saline on days 1, 2, 3, 5 ,7 and 9 (six doses,first two doses will be daily from the first day and last 4 doses will be every 2 days)

Group Type PLACEBO_COMPARATOR

normal saline

Intervention Type DRUG

injection

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Erythropoietin

injection

Intervention Type DRUG

normal saline

injection

Intervention Type DRUG

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

1. ≥ 36 weeks of gestational age.
2. whole body cooling within 6 hours after birth.
3. Perinatal depression based on at least one of the following:

1. Apgar score \< 5 at 10 minutes.
2. Need for resuscitation at 10 minutes.
3. pH \< 7.1 in cord and Base deficit ≥ 15 mmol/L.
4. Moderate or severe encephalopathy according to sernat and sernat staging.

Exclusion Criteria

1-Admitted after 24 hour of birth. 2-Birth weight \< 1800 g (e.g., intrauterine growth restriction) 3-Genetic or congenital condition that affects neurodevelopment. 3-Torch infection and neonatal sepsis. 4-complex congenital heart disease. 5-severe dysmorphic feature . 6-Microcephaly:Head circumference \< 2 stander deviations below mean for gestational age.

7-Polycythemia (hematocrit \> 65%). 8-Premature rupture of membrane or chorioamnionitis.
Maximum Eligible Age

24 Hours

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Assiut University

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

ASAli

principal investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Central Contacts

Reach out to these primary contacts for questions about participation or study logistics.

prof.Samia A Mohamed, MD

Role: CONTACT

Phone: 00201223971326

Email: [email protected]

dr Safwat M Abdel-Aziz, MD

Role: CONTACT

Phone: 00201003918080

Email: [email protected]

References

Explore related publications, articles, or registry entries linked to this study.

Kurinczuk JJ, White-Koning M, Badawi N. Epidemiology of neonatal encephalopathy and hypoxic-ischaemic encephalopathy. Early Hum Dev. 2010 Jun;86(6):329-38. doi: 10.1016/j.earlhumdev.2010.05.010. Epub 2010 Jun 16.

Reference Type BACKGROUND
PMID: 20554402 (View on PubMed)

Jacobs SE, Morley CJ, Inder TE, Stewart MJ, Smith KR, McNamara PJ, Wright IM, Kirpalani HM, Darlow BA, Doyle LW; Infant Cooling Evaluation Collaboration. Whole-body hypothermia for term and near-term newborns with hypoxic-ischemic encephalopathy: a randomized controlled trial. Arch Pediatr Adolesc Med. 2011 Aug;165(8):692-700. doi: 10.1001/archpediatrics.2011.43. Epub 2011 Apr 4.

Reference Type BACKGROUND
PMID: 21464374 (View on PubMed)

Zacharias R, Schmidt M, Kny J, Sifringer M, Bercker S, Bittigau P, Buhrer C, Felderhoff-Muser U, Kerner T. Dose-dependent effects of erythropoietin in propofol anesthetized neonatal rats. Brain Res. 2010 Jul 9;1343:14-9. doi: 10.1016/j.brainres.2010.04.081. Epub 2010 May 7.

Reference Type BACKGROUND
PMID: 20452333 (View on PubMed)

Zhu C, Kang W, Xu F, Cheng X, Zhang Z, Jia L, Ji L, Guo X, Xiong H, Simbruner G, Blomgren K, Wang X. Erythropoietin improved neurologic outcomes in newborns with hypoxic-ischemic encephalopathy. Pediatrics. 2009 Aug;124(2):e218-26. doi: 10.1542/peds.2008-3553. Epub 2009 Jul 27.

Reference Type BACKGROUND
PMID: 19651565 (View on PubMed)

Elmahdy H, El-Mashad AR, El-Bahrawy H, El-Gohary T, El-Barbary A, Aly H. Human recombinant erythropoietin in asphyxia neonatorum: pilot trial. Pediatrics. 2010 May;125(5):e1135-42. doi: 10.1542/peds.2009-2268. Epub 2010 Apr 12.

Reference Type BACKGROUND
PMID: 20385632 (View on PubMed)

Cirelli I, Bickle Graz M, Tolsa JF. Comparison of Griffiths-II and Bayley-II tests for the developmental assessment of high-risk infants. Infant Behav Dev. 2015 Nov;41:17-25. doi: 10.1016/j.infbeh.2015.06.004. Epub 2015 Aug 11.

Reference Type BACKGROUND
PMID: 26276119 (View on PubMed)

Frymoyer A, Juul SE, Massaro AN, Bammler TK, Wu YW. High-dose erythropoietin population pharmacokinetics in neonates with hypoxic-ischemic encephalopathy receiving hypothermia. Pediatr Res. 2017 Jun;81(6):865-872. doi: 10.1038/pr.2017.15. Epub 2017 Jan 18.

Reference Type BACKGROUND
PMID: 28099423 (View on PubMed)

Murray DM, Boylan GB, Ryan CA, Connolly S. Early EEG findings in hypoxic-ischemic encephalopathy predict outcomes at 2 years. Pediatrics. 2009 Sep;124(3):e459-67. doi: 10.1542/peds.2008-2190. Epub 2009 Aug 24.

Reference Type BACKGROUND
PMID: 19706569 (View on PubMed)

Bednarek N, Mathur A, Inder T, Wilkinson J, Neil J, Shimony J. Impact of therapeutic hypothermia on MRI diffusion changes in neonatal encephalopathy. Neurology. 2012 May 1;78(18):1420-7. doi: 10.1212/WNL.0b013e318253d589. Epub 2012 Apr 18.

Reference Type BACKGROUND
PMID: 22517107 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

EHIE

Identifier Type: -

Identifier Source: org_study_id