The following is a summary of “Whole-body hypothermia in mild neonatal encephalopathy: protocol for a multicentre phase III randomised controlled trial,” published in the July 2024 issue of Pediatrics by Garegrat et al.

Mild hypoxic-ischemic encephalopathy (HIE) is linked to suboptimal cognitive and learning outcomes at school age. While whole-body hypothermia has been shown to reduce death and disability following moderate or severe HIE in high-income countries, its safety and efficacy in cases of mild encephalopathy remain uncertain. 

The Cooling in Mild Encephalopathy (COMET) trial aims to determine whether whole-body hypothermia can enhance cognitive development in neonates with mild HIE.

The COMET trial is a phase III, multicenter, open-label, two-arm randomized controlled trial with masked outcome assessments. About 426 neonates with mild encephalopathy will be recruited from 50 to 60 NHS hospitals over a span of 2.5 years, following parental consent. Participants will be randomized to receive either 72 hours of whole-body hypothermia (33.5 ± 0.5°C) or normothermia (37.0 ± 0.5°C) within 6 hours of birth. Prior to recruitment, frontline clinical staff will be trained and certified in the expanded modified Sarnat staging for encephalopathy. Neurological assessments of all screened and recruited cases will be video recorded and centrally reviewed for quality assurance. If recruitment occurs at a non-cooling center, neonates in both study arms will be transferred to a cooling center for continued care post-randomization. All neonates will undergo continuous amplitude-integrated electroencephalography (aEEG) for at least the first 48 hours to monitor for seizures. Predefined safety outcomes will be documented, and data will be collected to evaluate healthcare resource utilization. A central team, blinded to trial group allocation, will assess neurodevelopmental outcomes at two years of age. The primary outcome measure is the mean difference in composite cognitive scores on the Bayley Scales of Infant and Toddler Development, 4th Edition.

The COMET trial will establish the safety and efficacy of whole-body hypothermia for treating mild hypoxic-ischemic encephalopathy, potentially informing national and international guidelines in high-income countries. Additionally, the trial will provide an economic assessment of the cost-effectiveness of whole-body hypothermia therapy for mild encephalopathy within the NHS. By addressing these critical aspects, the COMET trial aims to enhance the understanding and management of mild HIE, ultimately improving long-term cognitive outcomes for affected neonates.

Source: bmcpediatr.biomedcentral.com/articles/10.1186/s12887-024-04935-4