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Whole-body cooling for babies with mild neonatal encephalopathy

Whole-body Hypothermia Versus Normothermia in Mild Neonatal Encephalopathy: A Multicentre Randomised Controlled Trial

Phase 3 Interventional Imperial College London · NCT05889507

This trial will test whether lowering body temperature soon after birth helps newborns with mild hypoxic‑ischaemic encephalopathy have better development by age two.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment426 (estimated)
Ages1 Hour to 6 Hours
SexAll
SponsorImperial College London Academic / other
Locations39 sites (Naples and 38 other locations)
Trial IDNCT05889507 on ClinicalTrials.gov

What this trial studies

This is a phase III, multi‑centre, open‑label randomized trial comparing whole‑body hypothermia (33.5±0.5°C for 72 hours) started within six hours of birth versus targeted normothermia (37±0.5°C) in term newborns with mild hypoxic‑ischaemic encephalopathy. Babies are randomized at the birth hospital and transferred to a cooling centre if required, with outcome assessments masked to treatment allocation. The primary neurodevelopmental outcome is measured with the Bayley Scales of Infant and Toddler Development (Bayley‑IV) at 24 (±2) months; the protocol also includes a trial‑based economic evaluation. The trial includes an internal pilot and aims to inform national practice and guidelines across the NHS.

Who should consider this trial

Good fit: Eligible infants are those born at or after 36 weeks with birth weight ≥1800 g who show evidence of intrapartum hypoxia and meet clinical criteria for mild hypoxic‑ischaemic encephalopathy within six hours of birth.

Not a fit: Babies born before 36 weeks, with very low birth weight, major congenital anomalies, those with moderate or severe encephalopathy already managed under existing protocols, or those presenting after the treatment window are unlikely to be eligible or to benefit from this trial.

Why it matters

Potential benefit: If successful, cooling could improve cognitive and developmental outcomes at age two and lead to clearer national guidance and more consistent care.

How similar studies have performed: Therapeutic hypothermia is proven to improve outcomes in moderate and severe neonatal encephalopathy, but randomized evidence specifically for mild cases is limited and this trial addresses that gap.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

All babies born at or after 36 weeks of gestation with a birth weight of 1800g or more with birth acidosis or requiring resuscitation at birth will be screened for eligibility.

Parents will be approached for consent if the baby meets all the three (A + B + C) criteria below:

A. Evidence of intra-partum hypoxia-ischemia defined as any of - (i) Apgar score of \<6 at 10 minutes after birth; (ii) continued need for resuscitation, including endotracheal or mask ventilation, at 10 minutes after birth; (iii) severe birth acidosis defined as any occurrence of pH =\<7.00 or a Base deficit \>=16mmol/l in any cord or baby gas sample within 60 minutes of birth.

B. Evidence of mild hypoxic ischaemic encephalopathy defined as - two or more abnormal findings in any of the six categories of the modified Sarnat examination (level of consciousness, spontaneous activity, posture, tone, primitive reflexes, and autonomic nervous system) but not meeting the diagnosis of moderate or severe hypoxic ischaemic encephalopathy on a standardised examination performed by a certified examiner between 1 to 6 hours of age.

C. Normal amplitude on aEEG performed for at least 30 minutes between 1 to 6 hours of age. Normal amplitude will be defined as upper margin of the aEEG activity more than 10 microvolts and the lower margin more than 5 microvolts on a single channel aEEG.

Exclusion Criteria:

* Infants who meet the BAPM criteria for whole-body hypothermia
* Infants without encephalopathy defined as less than two abnormalities on structured neurological examination.
* Infants with major congenital or chromosomal anomalies identified prior to randomisation.
* Infants with birthweight \<1800g.
* Infants who have already received sedation, muscle relaxation, or anti-convulsants prior to neurological assessment.

Where this trial is running

Naples and 38 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Neonatal EncephalopathyNewborn Asphyxiatherapeutic hypothermia
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.