The CoolCot trial: active methods of therapeutic hypothermia for newborns with hypoxic ischaemic encephalopathy (HIE) during neonatal transport: a study protocol for a randomised controlled trial comparing battery-enabled servo-controlled cooling blankets and ice-gel pack methods.

Abstract

Background: Impaired oxygen delivery or blood flow to the brain around the time of birth can cause injury. Hypoxic ischaemic encephalopathy (HIE) is a leading cause of death and disability in term and near-term infants. Therapeutic hypothermia (TH) (reducing body temperature to 33-34 °C for 72 h after birth) is the only intervention available for infants with moderate-to-severe encephalopathy. TH should be initiated within 6 h of birth for maximum benefit. Many infants worldwide are not born in a centre where TH is possible, and transport is required for active TH. In Australia, the current method of active TH during transport involves ice-gel packs. There have been no prospective studies comparing active methods of TH in neonatal transport reporting short- and long-term outcomes. We aim to compare two active TH modalities: a battery servo-controlled cooling device and infant wrap (Criticool Mini and Cruewrap (Belmont Medical Technologies, MA, USA)) and standard care (ice-gel packs) for TH during the transport of newborns with HIE.

Methods: The CoolCot study will be conducted in the Newborn Emergency Transport Service of Western Australia (NETS WA), a single state-wide transport service. Eligible infants with confirmed or suspected HIE will be referred to NETS WA from healthcare facilities without tertiary health (TH) capacity in Western Australia. Following the arrival of the transport team, infants with informed consent will be randomly assigned to battery-enabled servo-controlled TH or standard care (ice-gel packs). The primary outcome will be the proportion of patients with a temperature in the range of 33.0-34.0 °C on arrival at the receiving unit. The secondary outcomes include the time to achieve the therapeutic temperature, the time spent out of the temperature range, the degree of temperature fluctuation and safety. Long-term measures: MRI brain findings (days 5-10 of life) and Bayley Scales of Infant Development assessment at 2 years.

Discussion: The CoolCot study is the first RCT to prospectively compare the effectiveness of active cooling methods in neonatal emergency transport. Reducing the time needed to achieve the target temperature is crucial in optimising neurodevelopmental outcomes. A key feature of this study is the neurodevelopmental assessment conducted at age two.

Trial registration: WHO ICTRP Registry/Australian New Zealand Clinical Trials Registry: ACTRN12623001298606p. The CoolCot trial was prospectively registered on 13th December 2023.