COMET Trial

Cooling in Mild Encephalopathy Trial

The COMET Trial is funded by the NIHR and is designed to answer the question: Research question: Does whole-body hypothermia to 33.5 ±0.5°C, initiated within 6 hours of birth and continued for 72 hours, improve cognitive development at two years of age after mild Hypoxic Ischemic Encephalopathy (HIE) compared with targeted normothermia at 37.0 ±0.5°C?

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, many have lower cognitive skills (thinking ability) at 2 years and over a third require special educational support at school. While higher body temperature (>38.0°C) increases brain injury, we do not know if brain recovery is better if babies with mild encephalopathy are nursed at normal body temperature (37.0 ±0.5°C) or at a lower body temperature (33.5 ±0.5°C). The aim of this study is to find out if a lower body temperature for first three to four days after birth is 1) safe 2) better than normal body temperature (37.0 ±0.5°C) for improving their cognitive ability at 2 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 6 hours of birth. If parents agree to participate in the trial, approximately half of the babies will be nursed at a low body temperature (33.5 ±0.5°C) for 3 days and the other half at normal body temperature (37.0 ±0.5°C). 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. Cooling may also cause shivering and doctors may give sedation to keep these babies comfortable.

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. All babies will also have an MRI scan before discharge home. At 2 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 5 ½ years, which includes 2 ½ recruitment and 2 years follow up. Consent from parents to assess these babies at school age (subject to future funding) will be also sought. The trial protocol was developed in close consultation with parents of babies who had mild encephalopathy, and representatives from a charity for babies with brain injury. Parents will continue to be involved in all aspects of this study. We will also closely work with the British Association of Perinatal Medicine and other international bodies so that the results from this study are rapidly incorporated into national and international guidelines.

People

Professor Samantha Johnson is a co-investigator on this project, leading the developmental follow-up of children at two years of age.

• More information is available on the NIHR website