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Optimising the Duration of Cooling in Mild Encephalopathy (COMET)

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ClinicalTrials.gov Identifier: NCT03409770
Recruitment Status : Recruiting
First Posted : January 24, 2018
Last Update Posted : June 5, 2020
Sponsor:
Collaborator:
Wayne State University
Information provided by (Responsible Party):
Thayyil, Sudhin

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

Condition or disease Intervention/treatment Phase
Neonatal Encephalopathy Hypothermia Neonatal Magnetic Resonance Spectroscopy Other: Therapeutic hypothermia Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 140 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Therapeutic hypothermia (33 to 34 C) for 2 different durations (48, or 72 h) and usual care (normothermia)
Masking: Single (Outcomes Assessor)
Masking Description: MR spectroscopy analysis will be masked to the allocation
Primary Purpose: Treatment
Official Title: Optimising the Duration of Cooling Therapy in Mild Neonatal Encephalopathy
Actual Study Start Date : October 10, 2019
Estimated Primary Completion Date : June 30, 2022
Estimated Study Completion Date : August 30, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Hypothermia

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




Primary Outcome Measures :
  1. Thalamic N-acetyl aspartate level [ Time Frame: 4 to 14 days after birth ]
    Feasibility of obtaining Proton MR spectroscopy thalamic N-acetyl aspartate level


Secondary Outcome Measures :
  1. Brain injury on conventional MR imaging [ Time Frame: 4 to 14 days after birth ]
    Cortical, white matter or deep nuclei injury

  2. Hospital stay [ Time Frame: Upto 30 days after birth ]
    Duration of hospital stay



Information from the National Library of Medicine

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Ages Eligible for Study:   up to 6 Hours   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03409770


Contacts
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Contact: Maria Morales 0044203 313 2473 m.moreno-morales@imperial.ac.uk
Contact: Maria Morales m.moreno-morales@imperial.ac.uk

Locations
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United States, Michigan
Wayne State University Not yet recruiting
Michigan Center, Michigan, United States, 48202
Contact: Seetha Shankaran, MD         
Contact: Sanjay Chawla, MD         
United Kingdom
Birmingham Womens Hospital Not yet recruiting
Birmingham, United Kingdom
Contact: Manobi Boorah, FRCPCH         
Medway NHS Foundation Trust Recruiting
Gillingham, United Kingdom
Contact: Dr Aung Soe, FRCPCH       aung.soe@medway.nhs.uk   
Contact: Russel Pryce, PhD         
Liverpool Womens Hospital Recruiting
Liverpool, United Kingdom
Contact: Kiran Yajamanym Yajamanym, FRCPCH    07809119027      
Homerton University Hospital Recruiting
London, United Kingdom
Contact: Narendra Aldangady         
Imperial College London Recruiting
London, United Kingdom
Contact: Sudhin Thayyil, PhD    07912888700    s.thayyil@imperial.ac.uk   
Contact: Pete Lally, PhD       p.lally@imperial.ac.uk   
The Newcastle Upon Tyne NHS Foundation Trust Recruiting
Newcastle, United Kingdom
Contact: Dr Sundeep Harigopal       sundeep.harigopal@nuth.nhs.uk   
Sponsors and Collaborators
Thayyil, Sudhin
Wayne State University
Investigators
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Principal Investigator: Sudhin Thayyil, PhD Imperial College London
Publications:

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Responsible Party: Thayyil, Sudhin
ClinicalTrials.gov Identifier: NCT03409770    
Other Study ID Numbers: 241031
37318 ( Registry Identifier: CPMS (NIHR Portfolio) )
First Posted: January 24, 2018    Key Record Dates
Last Update Posted: June 5, 2020
Last Verified: June 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Brain Diseases
Hypothermia
Central Nervous System Diseases
Nervous System Diseases
Body Temperature Changes