Erythropoietin in Management of Neonatal Hypoxic Ischemic Encephalopathy

NCT03163589 | Unknown Phase 3

• 1 other identifier: EHIE
• Study Type: interventional
• Target: 40
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Hypoxic-Ischemic Encephalopathy

Outcome Measures

Primary Outcomes (1)

• Death or long-term major neurodevelopmental disability according to Griffith score.

  The score is reported as normal if the score is between 85 and 114, mildly delayed if the score is 1 Stander deviation below the mean (\<85), and significantly delayed if the score is 2 Stander deviation below the mean (\<70)

  12 month

Secondary Outcomes (6)

• cerebral palsy

  12 month

• Epilepsy.

  12 month age.

• Magnetic resonance image evidence of brain injury.

  2-3 weeks after birth.

• Electroencephalogram evidence of brain injury.

  1 weeks after birth

• Adverse effect of erythropoietin

  12 months

Study Arms (2)

study group

EXPERIMENTAL

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)

Drug: Erythropoietin

control group

PLACEBO COMPARATOR

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)

Drug: normal saline

Interventions

Erythropoietin DRUG

injection

study group

normal saline DRUG

injection

control group

Eligibility Criteria

• Age: Up to 24 Hours
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• ≥ 36 weeks of gestational age.
• whole body cooling within 6 hours after birth.
• Perinatal depression based on at least one of the following:
• Apgar score \< 5 at 10 minutes.
• Need for resuscitation at 10 minutes.
• pH \< 7.1 in cord and Base deficit ≥ 15 mmol/L.
• Moderate or severe encephalopathy according to sernat and sernat staging.

You may not qualify if:

• 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.
• Polycythemia (hematocrit \> 65%). 8-Premature rupture of membrane or chorioamnionitis.

Sponsors & Collaborators

• Assiut University: lead

Related Publications (9)

• 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.

  PMID: 20554402 BACKGROUND

• 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.

  PMID: 21464374 BACKGROUND

• 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.

  PMID: 20452333 BACKGROUND

• 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.

  PMID: 19651565 BACKGROUND

• 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.

  PMID: 20385632 BACKGROUND

• 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.

  PMID: 26276119 BACKGROUND

• 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.

  PMID: 28099423 BACKGROUND

• 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.

  PMID: 19706569 BACKGROUND

• 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.

  PMID: 22517107 BACKGROUND

MeSH Terms

Conditions

Hypoxia-Ischemia, Brain

Interventions

Erythropoietin; Saline Solution

Condition Hierarchy (Ancestors)

Brain Ischemia; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Hypoxia, Brain; Vascular Diseases; Cardiovascular Diseases; Hypoxia; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Central Study Contacts

prof.Samia A Mohamed, MD

CONTACT

00201223971326; samiaatwa@gmail.com

dr Safwat M Abdel-Aziz, MD

CONTACT

00201003918080; Drsefwat90@yahoo.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: principal investigator

Study Record Dates

• First Submitted: May 18, 2017
• First Posted: May 23, 2017
• Study Start: December 1, 2017
• Primary Completion: December 1, 2019
• Study Completion: June 1, 2020
• Last Updated: May 31, 2017

Record last verified: 2017-05