Working…
Help guide our efforts to modernize ClinicalTrials.gov.
Send us your comments by March 14, 2020.
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

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.


Condition or disease Intervention/treatment Phase
Hypoxic-Ischemic Encephalopathy Drug: Erythropoietin Drug: normal saline Phase 3

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Effect of Erythropoietin and Hypothermia on Management of Neonatal Hypoxic Ischemic Encephalopathy
Estimated Study Start Date : December 1, 2017
Estimated Primary Completion Date : December 1, 2019
Estimated Study Completion Date : June 1, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Hypothermia

Arm Intervention/treatment
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)
Drug: Erythropoietin
injection

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)
Drug: normal saline
injection




Primary Outcome Measures :
  1. 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)


Secondary Outcome Measures :
  1. 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.

  2. Epilepsy. [ Time Frame: 12 month age. ]
    define as 2 or more afebrile unprovoked seizure.

  3. 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.

  4. 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

  5. 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.

  6. seizure [ Time Frame: during 2 weeks after birth ]
    number of clinical and electroencephalogram seizure



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   up to 24 Hours   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03163589


Contacts
Layout table for location contacts
Contact: prof.Samia A Mohamed, MD 00201223971326 samiaatwa@gmail.com
Contact: dr Safwat M Abdel-Aziz, MD 00201003918080 Drsefwat90@yahoo.com

Sponsors and Collaborators
Assiut University

Publications:

Layout table for additonal information
Responsible Party: ASAli, principal investigator, Assiut University
ClinicalTrials.gov Identifier: NCT03163589    
Other Study ID Numbers: EHIE
First Posted: May 23, 2017    Key Record Dates
Last Update Posted: May 31, 2017
Last Verified: May 2017

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Brain Diseases
Brain Ischemia
Hypoxia-Ischemia, Brain
Ischemia
Hypoxia
Pathologic Processes
Central Nervous System Diseases
Nervous System Diseases
Signs and Symptoms, Respiratory
Signs and Symptoms
Cerebrovascular Disorders
Vascular Diseases
Cardiovascular Diseases
Hypoxia, Brain
Epoetin Alfa
Hematinics