Optimising the Duration of Cooling in Mild Encephalopathy (COMET)

August 2, 2023 updated by: Thayyil, Sudhin

Optimising the Duration of Cooling Therapy in Mild Neonatal Encephalopathy

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

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Estimated)

140

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Italy
      • Naples, Italy
        • Luigi Vanvitelli Hospital
  • United Kingdom
      • Birmingham, United Kingdom
        • Birmingham Womens Hospital
      • Gillingham, United Kingdom
        • Medway NHS Foundation Trust
      • Liverpool, United Kingdom
        • Liverpool Womens Hospital
      • London, United Kingdom
        • Imperial College London
      • London, United Kingdom
        • Homerton University Hospital
      • Newcastle, United Kingdom
        • The Newcastle Upon Tyne NHS Foundation Trust
  • United States
    • Michigan
      • Michigan Center, Michigan, United States, 48202
        • Wayne State University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 6 hours (Child)

Accepts Healthy Volunteers

No

Description

INCLUSION CRITERIA

All of the following three criteria should be met:

  1. Age less than six hours. AND

  2. Evidence of acute perinatal asphyxia

    1. Metabolic acidosis (pH <7.0 and/or BE >-16) in cord gas or a blood gas within one of birth.

      OR

    2. If the pH or BE is borderline (pH<7.15 to 7.0) and/or BE >-10 to -16) in cord and/or blood gas within 1h of birth additional evidence of perinatal asphyxia is required, which includes either an acute obstetric event (e.g. cord prolapse, abruption, shoulder dystocia) OR Need for continued resuscitation or ventilation at 10 minutes and/or a 10 min Apgar score <6
  3. Evidence of mild NE (at-least two abnormalities) on an NICHD neurological examination performed between 1 and 6h of birth.

EXCLUSION CRITERIA

The following group of babies will be excluded prior to randomisation

  1. Babies without encephalopathy
  2. Babies with moderate or severe encephalopathy who meet the current NICE/AAP guidelines for cooling therapy.
  3. Babies with seizures (clinical and/or aEEG/EEG)
  4. Babies with moderate or severe abnormalities on aEEG voltage criteria.
  5. Babies with life threatening congenital malformations

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
No Intervention: Usual care
Usual care (normothermia) arm
Experimental: Therapeutic hypothermia - 48 h
Whole body cooling (33 to 34 C) for 48 hours
Other: Therapeutic hypothermia
Whole body cooling using a servo controlled device
Experimental: Therapeutic hypothermia - 72 h
Whole body cooling (33 to 34 C) for 72 hours
Other: Therapeutic hypothermia
Whole body cooling using a servo controlled device

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Thalamic N-acetyl aspartate level
Time Frame: 4 to 14 days after birth
Feasibility of obtaining Proton MR spectroscopy thalamic N-acetyl aspartate level
4 to 14 days after birth

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Brain injury on conventional MR imaging
Time Frame: 4 to 14 days after birth
Cortical, white matter or deep nuclei injury
4 to 14 days after birth
Hospital stay
Time Frame: Upto 30 days after birth
Duration of hospital stay
Upto 30 days after birth

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Thayyil, Sudhin

Collaborators

Wayne State University

Investigators

  • Principal Investigator: Sudhin Thayyil, PhD, Imperial College London

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 10, 2019

Primary Completion (Estimated)

June 30, 2024

Study Completion (Estimated)

August 30, 2024

Study Registration Dates

First Submitted

January 10, 2018

First Submitted That Met QC Criteria

January 17, 2018

First Posted (Actual)

January 24, 2018

Study Record Updates

Last Update Posted (Actual)

August 4, 2023

Last Update Submitted That Met QC Criteria

August 2, 2023

Last Verified

August 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 241031
  • 37318 (Registry Identifier: CPMS (NIHR Portfolio))

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Data can be shared unconditionally will be made available when scientific manuscripts are published.

Data that cannot be shared publicly (e.g. to protect patient confidentiality) will be by request only. The PI will review each request on case-by-case basis. Upon approval the data requester will be asked to sign a data sharing agreement.

IPD Sharing Time Frame

Data will be available 3 to 6 after the end of the study.

IPD Sharing Access Criteria

Unidentified data will be shared by publication. Request for data that affects patient confidentiality will review by the study PI on a case-by-case basis.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • ANALYTIC_CODE
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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