Erythropoietin in Management of Neonatal Hypoxic Ischemic Encephalopathy

May 29, 2017 updated by: ASAli, Assiut University

Effect of Erythropoietin and Hypothermia on Management of Neonatal Hypoxic Ischemic Encephalopathy

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Unknown

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
40

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

No older than 3 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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)
12 month

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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.
12 month
Epilepsy.
Time Frame: 12 month age.
define as 2 or more afebrile unprovoked seizure.
12 month age.
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.
2-3 weeks after birth.
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
1 weeks after birth
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.
12 months
seizure
Time Frame: during 2 weeks after birth
number of clinical and electroencephalogram seizure
during 2 weeks after birth

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Assiut University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 1, 2017

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2019

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 1, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 18, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 20, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 23, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 31, 2017

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 29, 2017

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2017

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • EHIE

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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