Cooling in Mild Encephalopathy (COMET) trial

Sponsor: Imperial College London

Funder: National Institute of Health and Care Research, Health Technology Assessment

ClinicalTrials.gov Identifier: NCT05889507

Trial start date: 14 May 2024

Trial duration: Five and half years

Participating sites: 40 NHS hospitals

Study summary:

One in every 1000 babies born in the UK sustain brain dysfunction (also known as mild encephalopathy) from a drop in oxygen in the womb around the time of birth. Babies with mild encephalopathy often are irritable and have problems with breathing and feeding requiring admission to a neonatal intensive care unit. Although these babies improve within a few days and get discharged home, may have lower cognitive skills (thinking ability) at two years and around 38% require special educational support at school.

While higher body temperature (>38⁰C) increases brain injury, we do not know if brain recovery is better if babies with mild encephalopathy are nursed at normal body temperature (37⁰C) or at a lower body temperature (33.5⁰C).

The aim of this study is to find out if a lower body temperature for first three days after birth is

Safe
Better than normal body temperature (37⁰C) for improving their cognitive ability at two years of age.

We will recruit 426 babies born at or after 36 weeks who require resuscitation at birth, diagnosed with mild encephalopathy from 60 NHS hospitals over 30 months. Eligible babies will be identified following a careful examination and a bedside brain wave activity recording within six hours of birth.

If parents agree to participate in the trial, approximately half of the babies will be nursed at a low body temperature (33.5⁰C) for three days and the other half at normal body temperature (37⁰C). Apart from the difference in the body temperature, babies in both groups will be treated identically in specialised neonatal intensive care units with careful monitoring of brain wave activity and for any complications such as brain or lung bleeding, clotting problems, or breathing difficulty. While maintaining normal temperature can be achieved by having a temperature probe in the baby’s bottom and nursing the baby in a normal incubator, lowering body temperature (cooling therapy) requires a special device and placing the baby on a cooling blanket or mattress.

If a baby is not born at a hospital with a specialist intensive care unit, they will be transferred to a nearby intensive care unit, irrespective of whether they are being nursed at a normal or lower body temperature. This is important as all babies with brain injury (mild encephalopathy) do require monitoring of their brain wave activity to identify seizures for at least two days after birth in a specialised unit.

All babies will also have an MRI scan before discharge home. At two years of age, a specially trained clinician will carefully assess the baby’s cognitive ability. If cooling therapy is safe and beneficial, we will also report the costs and a financial case for making this treatment available to all babies with mild encephalopathy in the NHS. On the other hand, if it is harmful or in-effective, it will no longer be offered to babies with mild encephalopathy.

The total trial duration is five and a half years, which includes two and a half years for recruitment and two years follow up. Consent from parents to assess these babies at school age (subject to future funding) will be also sought.