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: pactr.samrc.ac.za
Trial no.: PACTR202006515915908 Date of Approval: 22/06/2020
Trial Status: Retrospective registration - This trial was registered after enrolment of the first participant
TRIAL DESCRIPTION
Public title A comparative study of neuroprotective strategies in neonatal hypoxic ischaemic encephalopathy
Official scientific title A comparative study of neuroprotective strategies in neonatal hypoxic ischaemic encephalopathy
Brief summary describing the background and objectives of the trial Perinatal hypoxic ischaemic insult can cause significant morbidity and mortality in newborn period, and can result in death or severe neurodevelopmental impairment later in life. It is the leading cause of death in term newborns in South Africa. There is now conclusive evidence that therapeutic hypothermia (cooling) reduces the likelihood of death and of severe handicap in survivors, and it has become part of standard care in many places. What has not been proven is whether combining cooling with other neuroprotective strategies, or altering the method of providing cooling can improve on the beneficial effects of cooling. It is also not entirely clear how cooling exerts its beneficial effects, and which babies are ideal candidates for cooling. Inflammation has been shown to play a significant role in mediating brain injury after hypoxia ischaemia. It is postulated that Morphine might account for the greater treatment effect noted in one of the published studies (neo.nEURO.network trail), and it may exert this effect through its immunomodulatory properties. In resource-poor settings, it is particularly important to be able to select the most appropriate infants for clinical interventions, and to have relatively simple tools for predicting outcome. Purpose and scope: To study and compare the long term outcomes of newborn infants with HIE treated either with therapeutic hypothermia alone, or with therapeutic hypothermia + intravenous morphine at Tygerberg Children’s Hospital (followed up to 18 months of age). Primary outcome: to determine whether combining therapeutic hypothermia with another neuroprotective strategy (ie. morphine) improves survival to 18 months of age, and improves survival without major disability at 18 months of age. Secondary outcomes: Since length of time that markers may remain elevated may be important with regard to reflecting ongoing/arrested injury, correlation of several markers with the severity of the primary injury and outcome will be
Type of trial RCT
Acronym (If the trial has an acronym then please provide)
Disease(s) or condition(s) being studied Neonatal Diseases
Sub-Disease(s) or condition(s) being studied
Purpose of the trial Treatment: Other
Anticipated trial start date 06/07/2011
Actual trial start date 07/03/2012
Anticipated date of last follow up 01/02/2019
Actual Last follow-up date 16/11/2017
Anticipated target sample size (number of participants) 40
Actual target sample size (number of participants) 48
Recruitment status Completed
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
Factorial: participants randomly allocated to either no, one, some or all interventions simultaneously Randomised Simple randomization using a randomization table created by a computer software program Allocation was determined by the holder of the sequence who is situated off site Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group Morphine in children cooled for HIE 25ug/kg/hr 72hours IVI Cooling for 72 hours Morphine for 72 Hours re-warm for a minimum of 6 hours 24
Control Group Cooling No Morphine N/A 72 Hours Cooling for 72 hours No Morphine re-warm for a minimum of 6 hours 24 Active-Treatment of Control Group
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
1) 36 weeks gestation or greater 2) Birthweight of at least 1.8kg. 3) At least one of the following: a) need for resuscitation for ≥10 minutes, b) Apgar score ≤7 at 10 minutes, c)pH ≤7 or base deficit ≥16 on cord gas or infant blood within an hour of birth. 4) Seizures, or moderate to severe encephalopathy on clinical grounds, or a Thompson HIE score of at least 10 5) Less than 6 hours old at initiation of cooling 1) Less than 36 weeks 2) Birthweight less than 1.8kg. 3) Not meeting at least one of the following: a) need for resuscitation for ≥10 minutes, b) Apgar score ≤7 at 10 minutes, c)pH ≤7 or base deficit ≥16 on cord gas or infant blood within an hour of birth. 4) No Seizures and NO moderate to severe encephalopathy on clinical grounds, or a Thompson HIE score of at least 10 5) Older than 6 hours 6) congenital abnormalities 7) infants in whom intensive care is withdrawn New born: 0 Day-1 Month 0 Day(s) 0 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 23/07/2010 Stellenbosch University Faculty Health Science Health Research Ethics Committee
Ethics Committee Address
Street address City Postal code Country
Francie van Zijl Drive Parow South Africa Parow 7505 South Africa
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Primary outcome: to determine whether combining therapeutic hypothermia with another neuroprotective strategy (ie. morphine) improves survival to 18 months of age, and improves survival without major disability at 18 months of age. 18 months
Secondary Outcome Correlation of several biomarkers with the severity of the primary injury and outcome will be evaluated. 18 months
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Tygerberg Hospital Francie van Zijl Drive Parow 7505 South Africa
FUNDING SOURCES
Name of source Street address City Postal code Country
SAMRC Francie van Zijl Drive Parow 7505 South Africa
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor SAMRC Francie van Zijl Drive Parow 7505 South Africa Funding Agency
Secondary Sponsor Mary Rutherford Snt Thomas Hospital London United Kingdom Individual
Secondary Sponsor Department of Paediatrics and Child Health Francie van Zijl Drive Parow South Africa University
Secondary Sponsor Prof B Marais Childrens Hospital at Westmead Sydny Australia Individual
Secondary Sponsor Helena Rabie Francie van Zijl Drive Parow South Africa Individual
COLLABORATORS
Name Street address City Postal code Country
Mary Rutherford Stn Thomas Hospital London United Kingdom
Johann van Zyl Francie van Zijl Drive Parow South Africa
Netta van Zyl Francie van Zijl drive Parow South Africa
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Gugulabatembunamahlubi Kali kali@sun.ac.za 00270219389223 Francie van Zijl Drive
City Postal code Country Position/Affiliation
Parow South Africa Stellenbosch University
Role Name Email Phone Street address
Scientific Enquiries Gugulabatembunamahlubi Kali kali@sun.ac.za 0219389223 Francie van Zijl
City Postal code Country Position/Affiliation
Parow South Africa Stellenbosch University
Role Name Email Phone Street address
Public Enquiries Anita Fourie aec1@sun.ac.za +27219389506 Francie van Zij
City Postal code Country Position/Affiliation
parow South Africa Stellenbosch University
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes The data underlying the results of this study are available upon request because it contains potentially sensitive information. Interested researchers may contact the principal investigator after publication of results. For data access requests via email kali@sun.ac.za. Study Protocol After publication of the study results and provided requests are received and approved Approval by PI
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