Optimising the Duration of Cooling in Mild Encephalopathy

Not Applicable

Active, not recruiting

• Conditions: Neonatal Encephalopathy; Hypothermia Neonatal; Magnetic Resonance Spectroscopy
• Interventions: Other: Therapeutic hypothermia

• Registration Number: NCT03409770
• Lead Sponsor: Thayyil, Sudhin

Brief Summary

Phase II randomised control trial of whole body cooling in mild neonatal encephalopathy.

Detailed Description

Although therapeutic hypothermia for 72 hours reduces brain injury and improves long term neurodevelopmental outcomes after moderate or severe neonatal encephalopathy, the benefits and optimal duration of cooling therapy in mild encephalopathy is not known. Adverse neurodevelopmental outcomes at 2 years occur in 16% of babies with un-treated mild neonatal encephalopathy. In the phase I of the COMET trial, we have shown that it is feasible to identify and randomise babies with mild encephalopathy, and to obtain the primary outcome (proton MR spectroscopy levels of Thalamic N-acetyl Aspartate) accurately. The phase II of the COMET trial will examine the benefits and optimal duration of cooling therapy in babies with mild encephalopathy.

Research questions

1. Does whole body cooling initiated within 6 hours of birth and continued for 72 hours increase thalamic MR spectroscopy N-acetyl aspartate levels in babies with mild encephalopathy, when compared with those who are not cooled? (Cohort 1)

2. In babies with mild encephalopathy undergoing cooling therapy as clinical care, does rewarming at 48 hours as opposed to 72 hours result in similar thalamic N-acetyl aspartate levels? (Cohort 2)

Study Population Cohort 1: A total of 60 babies with mild encephalopathy (\>36 weeks; \>2Kg) aged less than 6 hours will be recruited from several tertiary neonatal units in the UK, Europe, USA and Canada, over a 2 year period. The babies will be randomised to usual care (no cooling) or cooling therapy (core temperature 33 to 34 C) for 72 hours within six hours of birth. MR imaging and spectroscopy will be performed between 4 to 14 days after birth.

Cohort 2: A total of 80 babies will mild encephalopathy (\>36 weeks; \>2Kg) aged 24 to 48 hours and undergoing cooling therapy as a part of standard clinical care will be recruited from several UK cooling centres, over a 2 year period. The babies will be randomised to rewarming after 48 hours or 72 hours of cooling therapy. MR imaging and spectroscopy will be performed between 4 to 14 days after birth. The babies recruited to cohort 1 will not be eligible for recruitment to cohort 2.

Primary outcome (both cohorts)

• Proton MR spectroscopy Thalamic N-acetyl aspartate levels between 4 to 14 days of age.

Benefits of the trial These data will inform the national and international guidelines on management of babies with mild neonatal encephalopathy. If a shorter duration of cooling is as good or better than 3 days of cooling, this will reduce the intensive care stays, opioid use and separation from parents.

Study Timeline

• Study First Submitted: 2018-01-10
• Study First Submitted QC: 2018-01-17
• Study First Posted: 2018-01-24
• Study Start: 2019-10-10
• Status Verified: 2023-08
• Last Update Submitted: 2023-08-02
• Last Update Posted: 2023-08-04
• Primary Completion: 2024-06-30
• Study Completion: 2024-08-30

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 140

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Therapeutic hypothermia - 48 h	Therapeutic hypothermia	Whole body cooling (33 to 34 C) for 48 hours
Therapeutic hypothermia - 72 h	Therapeutic hypothermia	Whole body cooling (33 to 34 C) for 72 hours

Primary Outcome Measures

Name	Time	Method
Thalamic N-acetyl aspartate level	4 to 14 days after birth	Feasibility of obtaining Proton MR spectroscopy thalamic N-acetyl aspartate level

Secondary Outcome Measures

Name	Time	Method
Hospital stay	Upto 30 days after birth	Duration of hospital stay
Brain injury on conventional MR imaging	4 to 14 days after birth	Cortical, white matter or deep nuclei injury

Trial Locations

Locations (8)

The Newcastle Upon Tyne NHS Foundation Trust; 🇬🇧 Newcastle, United Kingdom

Wayne State University; 🇺🇸 Michigan Center, Michigan, United States

Homerton University Hospital; 🇬🇧 London, United Kingdom

Imperial College London; 🇬🇧 London, United Kingdom

Birmingham Womens Hospital; 🇬🇧 Birmingham, United Kingdom

Luigi Vanvitelli Hospital; 🇮🇹 Naples, Italy

Medway NHS Foundation Trust; 🇬🇧 Gillingham, United Kingdom

Liverpool Womens Hospital; 🇬🇧 Liverpool, United Kingdom