An interventional study of Therapeutic hypothermia in Neonatal Encephalopathy, Hypothermia Neonatal and Magnetic Resonance Spectroscopy, sponsored by Thayyil, Sudhin. Active, not recruiting at 8 sites in 3 countries. Open to participants aged Up to 6 Hours. Per ClinicalTrials.gov, last updated 2023-08-04.
Sponsored by Thayyil, Sudhin · Not applicable, Interventional, and Treatment
Phase II randomised control trial of whole body cooling in mild neonatal encephalopathy.
Although therapeutic hypothermia for 72 hours reduces brain injury and improves long term neurodevelopmental outcomes after moderate or severe neonatal encephalopathy, the benefits and optimal duration of cooling therapy in mild encephalopathy is not known. Adverse neurodevelopmental outcomes at 2 years occur in 16% of babies with un-treated mild neonatal encephalopathy. In the phase I of the COMET trial, we have shown that it is feasible to identify and randomise babies with mild encephalopathy, and to obtain the primary outcome (proton MR spectroscopy levels of Thalamic N-acetyl Aspartate) accurately. The phase II of the COMET trial will examine the benefits and optimal duration of cooling therapy in babies with mild encephalopathy.
Research questions
Study Population Cohort 1: A total of 60 babies with mild encephalopathy (>36 weeks; >2Kg) aged less than 6 hours will be recruited from several tertiary neonatal units in the UK, Europe, USA and Canada, over a 2 year period. The babies will be randomised to usual care (no cooling) or cooling therapy (core temperature 33 to 34 C) for 72 hours within six hours of birth. MR imaging and spectroscopy will be performed between 4 to 14 days after birth.
Cohort 2: A total of 80 babies will mild encephalopathy (>36 weeks; >2Kg) aged 24 to 48 hours and undergoing cooling therapy as a part of standard clinical care will be recruited from several UK cooling centres, over a 2 year period. The babies will be randomised to rewarming after 48 hours or 72 hours of cooling therapy. MR imaging and spectroscopy will be performed between 4 to 14 days after birth. The babies recruited to cohort 1 will not be eligible for recruitment to cohort 2.
Primary outcome (both cohorts)
Benefits of the trial These data will inform the national and international guidelines on management of babies with mild neonatal encephalopathy. If a shorter duration of cooling is as good or better than 3 days of cooling, this will reduce the intensive care stays, opioid use and separation from parents.
All of the following three criteria should be met:
Evidence of acute perinatal asphyxia
Metabolic acidosis (pH \<7.0 and/or BE >-16) in cord gas or a blood gas within one of birth.
OR
EXCLUSION CRITERIA
The following group of babies will be excluded prior to randomisation
Usual care (normothermia) arm
Whole body cooling (33 to 34 C) for 48 hours
Other: Therapeutic hypothermia
Whole body cooling (33 to 34 C) for 72 hours
Other: Therapeutic hypothermia
Whole body cooling using a servo controlled device
Thalamic N-acetyl aspartate level
Feasibility of obtaining Proton MR spectroscopy thalamic N-acetyl aspartate level
Time frame: 4 to 14 days after birth
Brain injury on conventional MR imaging
Cortical, white matter or deep nuclei injury
Time frame: 4 to 14 days after birth
Hospital stay
Duration of hospital stay
Time frame: Upto 30 days after birth
Plan to share: Yes — Data can be shared unconditionally will be made available when scientific manuscripts are published. Data that cannot be shared publicly (e.g. to protect patient confidentiality) will be by request only. The PI will review each request on case-by-case basis. Upon approval the data requester will be asked to sign a data sharing agreement.
Supporting information: Study protocol, Sap, Icf, Csr, Analytic code
This study is active, not recruiting, as verified in Aug 2023. You cannot join it, but the record below documents what was studied.
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Thayyil, Sudhin