Pan African Clinical Trials Registry

South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0506 / +27 21 938 0834 Fax: +27 21 938 0836
Email: pactradmin@mrc.ac.za Website: www.pactr.org
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