Trial no.:	PACTR201812814507775	Date of Approval:	12/12/2018
Trial Status:	Registered in accordance with WHO and ICMJE standards

TRIAL DESCRIPTION

Public title

Erythropoietin and Magnesium Sulphate in Hypoxic Ischaemic Encelpalopathy

Official scientific title

The Role of Erythropoietin and Magnesium Sulphate in Hypoxic Ischaemic Encephalopathy: Hope for the Perinatally Asphyxiated

Brief summary describing the background and objectives of the trial

Perinatal asphyxia, more appropriately known as hypoxic-ischemic encephalopathy (HIE), is a clinical condition characterized by clinical and laboratory evidence of acute or subacute brain injury resulting from systemic hypoxemia and/or reduced cerebral blood flow in the newborn. It is the commonest etiology for neonatal encephalopathies and accounts for 23% of all term newborn deaths worldwide. While the incidence of severe perinatal asphyxia in resource-rich countries is about 0.1-0.3% of total births, some hospital based studies in Nigeria documented between 3.2% and 30% prevalence and it accounts for between 45% and 83% of perinatal mortalities in some Nigerian studies. Survivors of severe HIE are also at high risk of developing severe cognitive and/or motor impairment, seizure disorders, deafness, and vision loss. Therapeutic hypothermia is currently the gold standard for treating HIE. Other new interventions include high dose Erythropoietin (EPO) and Magnesium sulfate (MgSO4). EPO is a drug widely known in NICUs for the management of Anemia of prematurity. It has been found to also be a neuroprotective agent, with remarkable neuroprotective and neuro-regenerative effects. Its neuroprotective effects are especially prominent in damages related to ischemia-reperfusion injuries. The neuroprotective properties of Magnesium have also been demonstrated in several animal studies. Magnesium has beneficial effect in cerebral palsy reduction in preterm infants of mothers that received prenatal Magnesium sulfate. Given the level of poverty in our environment it is most reasonable to attempt to address issues of morbidities more proactively by targeting evidence based cost effective measures that will not only curtail mortality but will also enhance quality of life of survivors of PA. The present study aims to evaluate the neuro protective effects of EPO and MgSO4 in the management of severe PA in term infants at Lagos University Teaching Hospital, Lagos. All term newbor

Type of trial

RCT

Acronym (If the trial has an acronym then please provide)

Disease(s) or condition(s) being studied

Neonatal Diseases,Pregnancy and Childbirth

Sub-Disease(s) or condition(s) being studied

Purpose of the trial

Treatment: Drugs

Anticipated trial start date

17/02/2020

Actual trial start date

10/02/2020

Anticipated date of last follow up

30/12/2022

Actual Last follow-up date

30/07/2020

Anticipated target sample size (number of participants)

120

Actual target sample size (number of participants)

120

Recruitment status

Active, not recruiting

Publication URL

Secondary Ids	Issuing authority/Trial register

STUDY DESIGN
Intervention assignment	Allocation to intervention	If randomised, describe how the allocation sequence was generated	Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms	Masking	If masking / blinding was used
Parallel: different groups receive different interventions at same time during study	Randomised	Simple randomization using a randomization table created by a computer software program	Sealed opaque envelopes	Masking/blinding used	Outcome Assessors

INTERVENTIONS
Intervention type	Intervention name	Dose	Duration	Intervention description	Group size	Nature of control
Experimental Group	Erythropoietin	1000IU/kg daily	Five days	Group A will receive 1000IU/kg of Erythropoietin intravenously stat on admission then daily for five days.	40
Experimental Group	Magnesium Sulfate	250mg/kg daily	Three days	Group B will receive Magnesium Sulfate infusion at 250 mg/kg per dose (1 mL/kg per dose in 20 mL of 5% dextrose solution) over 1 hour stat on admission, then daily for three doses.	40
Control Group	Normal Saline	2ml daily	Five days	Group C will receive 2ml of 0.9% Saline stat on admission then daily for five days.	40	Placebo

ELIGIBILITY CRITERIA
List inclusion criteria	List exclusion criteria	Age Category	Minimum age	Maximum age	Gender
All term newborns (≥ 37weeks gestation) diagnosed of perinatal asphyxia at admission and who are <72 hours of age. Evidence of Perinatal depression based on delayed cry at birth and at least one criteria on Sarnat and Sarnat HIE grading	Severe congenital anomalies Preterm babies Infants >72 hours of age at time of presentation /consent Those in which consent could not be obtained Evidence of sepsis (confirmed according to unit protocol)	New born: 0 Day-1 Month	0 Day(s)	3 Day(s)	Both

ETHICS APPROVAL

Has the study received appropriate ethics committee approval

Date the study will be submitted for approval

Date of approval

Name of the ethics committee

Yes

28/11/2018

Lagos University Teaching Hospital Health research Ethics Committee

Ethics Committee Address
Street address	City	Postal code	Country
Room 107, First floor LUTH administrative block	Lagos	2517	Nigeria

OUTCOMES
Type of outcome	Outcome	Timepoint(s) at which outcome measured
Primary Outcome	Survival at discharge or Death within the first two years of life and Neurodevelopmental impairment at 6, 12, 18 and 24 months of age	Discharge, 6,12,18 and 24 months
Secondary Outcome	Association between the levels of NRBC and NRBC/100WBC with neonatal outcome Safety of the medications based on the presence or absence of any adverse event	On and during admission

RECRUITMENT CENTRES
Name of recruitment centre	Street address	City	Postal code	Country
Lagos University Teaching Hospital	Ishaga Road, Idiaraba	Lags	2517	Nigeria

FUNDING SOURCES
Name of source	Street address	City	Postal code	Country
Ezenwa Beatrice	Department of Paediatrics, Lagos University Teaching Hospital	Lagos		Nigeria

SPONSORS
Sponsor level	Name	Street address	City	Postal code	Country	Nature of sponsor
Primary Sponsor	Ezenwa Beatrice	Dept of Paediatrics, LUTH	Lagos		Nigeria	Individual

COLLABORATORS
Name	Street address	City	Postal code	Country
Ezeaka Chinyere	Neonatology unit, Dept of Paediatrics, LUTH	Lagos		Nigeria
Fajolu Iretiola	Neonatology unit, Dept of Paediatrics, LUTH	Lagos		Nigeria
Ogbenna Ann	Dept of Haematology and Blood transfusion, LUTH	Lagos		Nigeria
Olowoyeye Omodele	Dept of Radiodiagnosis, LUTH	Lagos		Nigeria
Akinsola Oluwatosin	Dept of Community Health and Primary Care, CMUL	Lagos		Nigeria

CONTACT PEOPLE
Role	Name	Email	Phone	Street address
Principal Investigator	Beatrice Ezenwa	beatriceezenwa@yahoo.com	+2348051403189	Dept of Pediatrcs, LUTH
City	Postal code	Country	Position/Affiliation
Lagos		Nigeria	Consultant Pediatrician LUTH
Role	Name	Email	Phone	Street address
Public Enquiries	Beatrice Ezenwa	beatriceezenwa@yahoo.com	+2348051403189	Dept of Paediatrics LUTH
City	Postal code	Country	Position/Affiliation
Lagos		Nigeria	Consultant Pediatrician
Role	Name	Email	Phone	Street address
Scientific Enquiries	Beatrice Ezenwa	beatriceezenwa@yahoo.com	+2348051403189	Dept of Pediatrics, LUTH
City	Postal code	Country	Position/Affiliation
Lagos		Nigeria	Consultant Pediatrician

REPORTING
Share IPD	Description	Additional Document Types	Sharing Time Frame	Key Access Criteria
No
URL	Results Available	Results Summary	Result Posting Date	First Journal Publication Date
	No
Result Upload 1:	Result Upload 2:	Result Upload 3:	Result Upload 4:	Result Upload 5:

Result URL Hyperlinks	Link To Protocol
Result URL Hyperlinks

Changes to trial information
Section Name	Field Name	Date	Reason	Old Value	Updated Value
Trial Information	Public title	10/12/2018	edit	ERYTHROPOIETIN AND MAGNESIUM SULPHATE IN HYPOXIC ISCHAEMIC ENCEPHALOPATHY	Erythropoietin and Magnesium Sulphate in Hypoxic Ischaemic Encelpalopathy
Section Name	Field Name	Date	Reason	Old Value	Updated Value
Trial Information	Official scientific title	10/12/2018	edit	THE ROLE OF ERYTHROPOIETIN AND MAGNESIUM SULPHATE IN HYPOXIC ISCHAEMIC ENCEPHALOPATHY: HOPE FOR THE PERINATALLY ASPHYXIATED	The Role of Erythropoietin and Magnesium Sulphate in Hypoxic Ischaemic Encephalopathy: Hope for the Perinatally Asphyxiated
Section Name	Field Name	Date	Reason	Old Value	Updated Value
Trial Information	Trial description	10/12/2018	edit	Perinatal asphyxia, more appropriately known as hypoxic-ischemic encephalopathy (HIE), is a clinical condition characterized by clinical and laboratory evidence of acute or subacute brain injury resulting from systemic hypoxemia and/or reduced cerebral blood flow in the newborn. It is the commonest etiology for neonatal encephalopathies and accounts for 23% of all term newborn deaths worldwide. While the incidence of severe perinatal asphyxia in resource-rich countries is about 0.1-0.3% of total births, some hospital based studies in Nigeria documented between 3.2% and 30% prevalence and it accounts for between 45% and 83% of perinatal mortalities in some Nigerian studies. Survivors of severe HIE are also at high risk of developing severe cognitive and/or motor impairment, seizure disorders, deafness, and vision loss. Therapeutic hypothermia is currently the gold standard for treating HIE. Other new interventions include high dose Erythropoietin (EPO) and Magnesium sulfate (MgSO4). EPO is a drug widely known in NICUs for the management of Anemia of prematurity. It has been found to also be a neuroprotective agent, with remarkable neuroprotective and neuro-regenerative effects. Its neuroprotective effects are especially prominent in damages related to ischemia-reperfusion injuries. The neuroprotective properties of Magnesium have also been demonstrated in several animal studies. Magnesium has beneficial effect in cerebral palsy reduction in preterm infants of mothers that received prenatal Magnesium sulfate. Given the level of poverty in our environment it is most reasonable to attempt to address issues of morbidities more proactively by targeting evidence based cost effective measures that will not only curtail mortality but will also enhance quality of life of survivors of PA. The present study aims to evaluate the neuro protective effects of EPO and MgSO4 in the management of severe PA in term infants at Lagos University Teaching Hospital, Lagos. All term newborns (≥ 37 weeks gestation) diagnosed of perinatal asphyxia at admission and who are <72 hours of age will be recruited and randomized into two groups. Group A will receive high dose Erythropoietin, Group B will receive standard dose of MgSO4 while Group C will not receive any of the drugs but will receive intravenous normal saline as a placebo. All the participants will be offered standard care according to the unit protocol for perinatal asphyxia. Clinical course and baseline characteristics will be recorded on a pre-designed proforma. All participants will undergo a cranial ultrasound scanning, MRI studies and EEG monitoring looking for abnormalities characteristic of HIE. Outcome measures include death or neurodevelopmental impairment at discharge.	Perinatal asphyxia, more appropriately known as hypoxic-ischemic encephalopathy (HIE), is a clinical condition characterized by clinical and laboratory evidence of acute or subacute brain injury resulting from systemic hypoxemia and/or reduced cerebral blood flow in the newborn. It is the commonest etiology for neonatal encephalopathies and accounts for 23% of all term newborn deaths worldwide. While the incidence of severe perinatal asphyxia in resource-rich countries is about 0.1-0.3% of total births, some hospital based studies in Nigeria documented between 3.2% and 30% prevalence and it accounts for between 45% and 83% of perinatal mortalities in some Nigerian studies. Survivors of severe HIE are also at high risk of developing severe cognitive and/or motor impairment, seizure disorders, deafness, and vision loss. Therapeutic hypothermia is currently the gold standard for treating HIE. Other new interventions include high dose Erythropoietin (EPO) and Magnesium sulfate (MgSO4). EPO is a drug widely known in NICUs for the management of Anemia of prematurity. It has been found to also be a neuroprotective agent, with remarkable neuroprotective and neuro-regenerative effects. Its neuroprotective effects are especially prominent in damages related to ischemia-reperfusion injuries. The neuroprotective properties of Magnesium have also been demonstrated in several animal studies. Magnesium has beneficial effect in cerebral palsy reduction in preterm infants of mothers that received prenatal Magnesium sulfate. Given the level of poverty in our environment it is most reasonable to attempt to address issues of morbidities more proactively by targeting evidence based cost effective measures that will not only curtail mortality but will also enhance quality of life of survivors of PA. The present study aims to evaluate the neuro protective effects of EPO and MgSO4 in the management of severe PA in term infants at Lagos University Teaching Hospital, Lagos. All term newbor
Section Name	Field Name	Date	Reason	Old Value	Updated Value
Ethics	Ethics List	12/12/2018	Ethics approval attached	TRUE, Lagos University Teaching Hospital Health research Ethics Committee, Room 107, First floor LUTH administrative block, Lagos, 2517, Nigeria, , 28 Nov 2018, +23415850737, luthethics@yahoo.com,	TRUE, Lagos University Teaching Hospital Health research Ethics Committee, Room 107, First floor LUTH administrative block, Lagos, 2517, Nigeria, , 28 Nov 2018, +23415850737, luthethics@yahoo.com, 5756_4047_4737.pdf
Section Name	Field Name	Date	Reason	Old Value	Updated Value
Funding Source	FundingSources List	12/12/2018	Funding source added		Ezenwa Beatrice, Department of Paediatrics, Lagos University Teaching Hospital, Lagos, , Nigeria, Self Funded,
Section Name	Field Name	Date	Reason	Old Value	Updated Value
Reporting	Plan to share IPD	12/12/2018	update	Undecided	No
Section Name	Field Name	Date	Reason	Old Value	Updated Value
Trial Information	Anticipated trial start date	23/09/2019	To obtain grant for the study	01 Jan 2019	02 Oct 2019
Section Name	Field Name	Date	Reason	Old Value	Updated Value
Trial Information	Actual trial start date	23/09/2019	Finally obtained grant for the trial	15 Jan 2019	14 Oct 2019
Section Name	Field Name	Date	Reason	Old Value	Updated Value
Trial Information	Recruitment status	23/09/2019	Putting logistics in order before commencing	Not yet recruiting	Active, not recruiting
Section Name	Field Name	Date	Reason	Old Value	Updated Value
Trial Information	Anticipated trial start date	31/01/2020	To be able to put all the trial logistics in order	02 Oct 2019	17 Feb 2020
Section Name	Field Name	Date	Reason	Old Value	Updated Value
Trial Information	Actual trial start date	31/01/2020	To be able to put all the trial logistics in order	14 Oct 2019	10 Feb 2020
Section Name	Field Name	Date	Reason	Old Value	Updated Value
Trial Information	Anticipated date of last follow up	31/01/2020	To accommodate the new start date	30 Jun 2022	30 Dec 2022
Section Name	Field Name	Date	Reason	Old Value	Updated Value
Trial Information	Completion date	31/01/2020	To accommodate the new start date	31 Jan 2022	30 Jul 2020

Pan African Clinical Trials Registry