Ignite Creation Date:
2024-05-06 @ 7:05 PM
Last Modification Date:
2024-10-26 @ 3:00 PM
Study NCT ID:
NCT05889507
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-03-20
First Post:
2023-05-12
Brief Title:
Cooling in Mild Encephalopathy
Sponsor:
Imperial College London
Organization:
Imperial College London
Study Overview
Official Title:
Whole-body Hypothermia Versus Normothermia in Mild Neonatal Encephalopathy A Multicentre Randomised Controlled Trial
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
COMET
Brief Summary:
The goal of this randomised control trial is to establish the safety and efficacy of whole-body hypothermia for babies with mild hypoxic ischaemic encephalopathy inform national and international guidelines and establish uniform practice across the NHS
The main questions it aims to answer are
1 Does whole-body cooling 33505C initiated within six hours of birth and continued for 72 hours improve cognitive development at 24 2 months of age after mild neonatal encephalopathy compared with normothermia 3705C
2 Does a prospective trial-based economic evaluation support the provision of cooling therapy for mild encephalopathy in the NHS on cost-effectiveness grounds
Participants will have the following interventions
Randomisation into one of the following groups
Whole body hypothermia group
Targeted normothermia group
Bayley Scales of Infant and Toddler Development 4th Edition Bayley-IV examination at 24 2 months of age
Researchers will compare the mean Cognitive Composite Scale score from the Bayley IV examination between the two groups
The main questions it aims to answer are
1 Does whole-body cooling 33505C initiated within six hours of birth and continued for 72 hours improve cognitive development at 24 2 months of age after mild neonatal encephalopathy compared with normothermia 3705C
2 Does a prospective trial-based economic evaluation support the provision of cooling therapy for mild encephalopathy in the NHS on cost-effectiveness grounds
Participants will have the following interventions
Randomisation into one of the following groups
Whole body hypothermia group
Targeted normothermia group
Bayley Scales of Infant and Toddler Development 4th Edition Bayley-IV examination at 24 2 months of age
Researchers will compare the mean Cognitive Composite Scale score from the Bayley IV examination between the two groups
Detailed Description:
COMET is a phase III prospective multi-centre open label two-arm randomised controlled trial with an internal pilot and masked outcome assessments Administration of cooling therapy cannot be masked
All babies born at or after 36 weeks and requiring prolonged resuscitation at birth defined as continued resuscitation at 10 minutes after birth or 10-minute Apgar score less than 6 or those with severe birth acidosis defined as any occurrence of pH 700 or Base deficit 16mmoll in any cord or baby gas sample within 60 minutes of birth and admitted to the neonatal unit will started on aEEG or EEG as a part of standard clinical care
Neonatal doctors or advanced nurse practitioners clinical team will screen for eligibility using a structured neurological examination performed between 1 to 6 hours after birth
Once parental consent is obtained babies will be randomised to whole-body hypothermia or targeted normothermia within 6 hours of birth using a web-based program Initial assessment and randomisation and initiation of whole-body hypothermia or targeted normothermia will occur at the hospital of birth The babies in both arms who are born at a non-cooling centre LNU or SCBU will be then transferred to the nearest cooling centre NICU within 8 hours of birth for continued care
Whole-body hypothermia 33505C will be initiated within 6 hours of birth and continued for 72 hours using a servo-controlled cooling machine at the nearest available neonatal intensive care unit cooling centre Passive cooling methods will not be allowed Whole-body hypothermia to 33505C for 72 hours is the duration and depth of cooling that is standard for babies with moderate or severe HIE in the NHS To administer this intervention babies will be kept on a cooling mattress or blanket circulating a coolantwater a rectal temperature probe will be inserted and overhead radiant warmers will be switched off The cooling device will be set to hypothermia mode and body temperature will be rapidly reduced to 335C from 370C and maintained within the target range of 33C to 34C
In the Normothermia Control group the rectal temperature will be maintained at 37005C using servo-controlled incubators for the first 88 hours and any hyperthermia will be treated with a standardised protocol Rectal temperature will be recorded as in the whole-body hypothermia group Continuous axillary temperature will be recorded during the first 88 hours Babies in the control group who develop seizures level 1 or level 2 and progress to moderate HIE between 6 to 24 hours may be treated with whole-body cooling for 72 hours as clinical care although this is expected to occur in less than 5
Conventional MRI using standard 3D T1-weighted and 2D T2-weighted sequences and diffusion weighted imaging will be performed in all babies prior to discharge home
The follow-up assessment will be done when the recruited babies are 24 2 months of age The assessment will be carried out using the Bayley Scales of Infant and Toddler Development IV It is a validated and standardized scoring system that assesses development in three domains that is cognition language and motor development In addition all infants will have a detailed neurological examination including Gross Motor Function Classification System GMFCS for cerebral palsy vision and hearing assessment Babies who die the mortality rate is expected to be less than 1 in mild HIE or who cannot be assessed with the Bayley-IV due to severe disability will be allocated a Cognitive Scale Composite score one point below the basal test score ie score of 54 In all infants PARCA-R online or face to face will be completed by the parents immediately prior to the Bayley IV assessments and CBCL face to face only after the Bayley IV assessments
The data will be collected into a paper case report form CRF initially and then entered into electronic database at the participating sites Data will include ante-natal birth and neonatal clinical information including gestational age birth weight gender Apgar scores birth history delivery room resuscitation to assess the baseline comparability of the groups core body temperature for assessment of intervention details of the hospital course laboratory investigations and MR imaging for safety monitoring and neurodevelopmental outcomes at 24 2 months of age for primary outcome evaluation
All babies born at or after 36 weeks and requiring prolonged resuscitation at birth defined as continued resuscitation at 10 minutes after birth or 10-minute Apgar score less than 6 or those with severe birth acidosis defined as any occurrence of pH 700 or Base deficit 16mmoll in any cord or baby gas sample within 60 minutes of birth and admitted to the neonatal unit will started on aEEG or EEG as a part of standard clinical care
Neonatal doctors or advanced nurse practitioners clinical team will screen for eligibility using a structured neurological examination performed between 1 to 6 hours after birth
Once parental consent is obtained babies will be randomised to whole-body hypothermia or targeted normothermia within 6 hours of birth using a web-based program Initial assessment and randomisation and initiation of whole-body hypothermia or targeted normothermia will occur at the hospital of birth The babies in both arms who are born at a non-cooling centre LNU or SCBU will be then transferred to the nearest cooling centre NICU within 8 hours of birth for continued care
Whole-body hypothermia 33505C will be initiated within 6 hours of birth and continued for 72 hours using a servo-controlled cooling machine at the nearest available neonatal intensive care unit cooling centre Passive cooling methods will not be allowed Whole-body hypothermia to 33505C for 72 hours is the duration and depth of cooling that is standard for babies with moderate or severe HIE in the NHS To administer this intervention babies will be kept on a cooling mattress or blanket circulating a coolantwater a rectal temperature probe will be inserted and overhead radiant warmers will be switched off The cooling device will be set to hypothermia mode and body temperature will be rapidly reduced to 335C from 370C and maintained within the target range of 33C to 34C
In the Normothermia Control group the rectal temperature will be maintained at 37005C using servo-controlled incubators for the first 88 hours and any hyperthermia will be treated with a standardised protocol Rectal temperature will be recorded as in the whole-body hypothermia group Continuous axillary temperature will be recorded during the first 88 hours Babies in the control group who develop seizures level 1 or level 2 and progress to moderate HIE between 6 to 24 hours may be treated with whole-body cooling for 72 hours as clinical care although this is expected to occur in less than 5
Conventional MRI using standard 3D T1-weighted and 2D T2-weighted sequences and diffusion weighted imaging will be performed in all babies prior to discharge home
The follow-up assessment will be done when the recruited babies are 24 2 months of age The assessment will be carried out using the Bayley Scales of Infant and Toddler Development IV It is a validated and standardized scoring system that assesses development in three domains that is cognition language and motor development In addition all infants will have a detailed neurological examination including Gross Motor Function Classification System GMFCS for cerebral palsy vision and hearing assessment Babies who die the mortality rate is expected to be less than 1 in mild HIE or who cannot be assessed with the Bayley-IV due to severe disability will be allocated a Cognitive Scale Composite score one point below the basal test score ie score of 54 In all infants PARCA-R online or face to face will be completed by the parents immediately prior to the Bayley IV assessments and CBCL face to face only after the Bayley IV assessments
The data will be collected into a paper case report form CRF initially and then entered into electronic database at the participating sites Data will include ante-natal birth and neonatal clinical information including gestational age birth weight gender Apgar scores birth history delivery room resuscitation to assess the baseline comparability of the groups core body temperature for assessment of intervention details of the hospital course laboratory investigations and MR imaging for safety monitoring and neurodevelopmental outcomes at 24 2 months of age for primary outcome evaluation
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None