Cooling in Mild Encephalopathy

Summary

The goal of this randomised control trial is to establish the safety and efficacy of whole-body hypothermia for babies with mild hypoxic ischaemic encephalopathy, inform national and international guidelines, and establish uniform practice across the NHS.

The main questions it aims to answer are:

1. Does whole-body cooling (33.5±0.5°C) initiated within six hours of birth and continued for 72 hours, improve cognitive development at 24 (±2) months of age after mild neonatal encephalopathy compared with normothermia (37±0.5°C)?
2. Does a prospective trial-based economic evaluation support the provision of cooling therapy for mild encephalopathy in the NHS on cost-effectiveness grounds?

Participants will have the following interventions:

* Randomisation into one of the following groups

* Whole body hypothermia group
* Targeted normothermia group
* Bayley Scales of Infant and Toddler Development 4th Edition (Bayley-IV) examination at 24 (±2) months of age.

Researchers will compare the mean Cognitive Composite Scale score from the Bayley IV examination between the two groups.

Conditions

• Neonatal Encephalopathy
• Newborn Asphyxia

Interventions

PROCEDURE

Whole body hypothermia

Whole-body hypothermia (33.5±0.5°C) initiated within 6 hours of birth and continued for 72 hours. The rectal temperature will be maintained at 33.5±0.5°C using a servo-controlled cooling machine.

PROCEDURE

Targeted normothermia

The axillary temperature will be maintained at 37±0.5°C for the first 80 hours and any hyperthermia will be treated with a standardised protocol.

OTHER

Supportive neonatal intensive care

Neonatal intensive care monitoring and support including ventilatory and inotropic support as clinically indicated

DIAGNOSTIC_TEST

Follow up assessment at 2 years of age

The assessment will be carried out using the Bayley Scales of Infant and Toddler Development IV. In addition, all infants will have a detailed neurological examination, including Gross Motor Function Classification System (GMFCS) for cerebral palsy, vision, and hearing assessment. Babies who die or who cannot be assessed with the Bayley-IV due to severe disability will be allocated a Cognitive Scale Composite score one point below the basal test score. PARCA-R will be completed by the parents immediately.

Sponsors & Collaborators

• Imperial College London

  lead OTHER

Principal Investigators

• Sudhin Thayyil, PhD · Imperial College London

• Seetha Shankaran, MD · Wayne State University

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Model

PARALLEL

Eligibility

Min Age

1 Hour

Max Age

6 Hours

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2024-03-15

Primary Completion

2030-01-01

Completion

2030-01-01

Countries

• Italy
• United Kingdom

Study Locations