Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Erythropoietin in Management of Neonatal Hypoxic Ischemic Encephalopathy

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03163589
Recruitment Status : Not yet recruiting
First Posted : May 23, 2017
Last Update Posted : May 31, 2017
Sponsor:
Information provided by (Responsible Party):
ASAli, Assiut University

Tracking Information
First Submitted Date  ICMJE May 18, 2017
First Posted Date  ICMJE May 23, 2017
Last Update Posted Date May 31, 2017
Estimated Study Start Date  ICMJE December 1, 2017
Estimated Primary Completion Date December 1, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 20, 2017)
Death or long-term major neurodevelopmental disability according to Griffith score. [ Time Frame: 12 month ]
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)
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 20, 2017)
  • cerebral palsy [ Time Frame: 12 month ]
    Presence and type of cerebral palsy determined using a standardized neurologic examination: no cerebral palsy,diplegic cerebral palsy,hemiplegic cerebral palsy, quadriplegic cerebral palsy.
  • Epilepsy. [ Time Frame: 12 month age. ]
    define as 2 or more afebrile unprovoked seizure.
  • Magnetic resonance image evidence of brain injury. [ Time Frame: 2-3 weeks after birth. ]
    The magnetic resonant imaging global scores will range from 48 to 186. score at 48 showing no evidence of acute injury; injury considers mild if the global score will between 49and 59, moderate if between 60 and 80 and severe if more than 81.
  • Electroencephalogram evidence of brain injury. [ Time Frame: 1 weeks after birth ]
    EEG will be graded in to normal ,mild ,severe and isoelectric using EEG score according to Murray et al 2009
  • Adverse effect of erythropoietin [ Time Frame: 12 months ]
    A-Hypertension: a systolic blood pressure in a neonate which is above 95th percentile for age and sex on three separate occasions; B- thrombotic events; C-polycythemia: central venous hematocrit of greater than 65%. D- red cell aplasia secondary to antierythropoietic antibodies. OR any other adverse effect appear during hospital stay or follow up.
  • seizure [ Time Frame: during 2 weeks after birth ]
    number of clinical and electroencephalogram seizure
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Erythropoietin in Management of Neonatal Hypoxic Ischemic Encephalopathy
Official Title  ICMJE Effect of Erythropoietin and Hypothermia on Management of Neonatal Hypoxic Ischemic Encephalopathy
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.

Detailed Description

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Hypoxic-Ischemic Encephalopathy
Intervention  ICMJE
  • Drug: Erythropoietin
    injection
  • Drug: normal saline
    injection
Study Arms  ICMJE
  • Experimental: 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)
    Intervention: Drug: Erythropoietin
  • Placebo Comparator: 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)
    Intervention: Drug: normal saline
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: May 20, 2017)
40
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 1, 2020
Estimated Primary Completion Date December 1, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 24 Hours   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: prof.Samia A Mohamed, MD 00201223971326 samiaatwa@gmail.com
Contact: dr Safwat M Abdel-Aziz, MD 00201003918080 Drsefwat90@yahoo.com
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03163589
Other Study ID Numbers  ICMJE EHIE
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party ASAli, Assiut University
Study Sponsor  ICMJE Assiut University
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Assiut University
Verification Date May 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP