Xenon and Cooling Therapy in Babies at High Risk of Brain Injury Following Poor Condition at Birth (CoolXenon3)

January 3, 2023 updated by: University Hospitals Bristol and Weston NHS Foundation Trust

Xenon and Cooling Therapy in Babies at High Risk of Brain Injury Following Poor Condition at Birth: A Randomised Pilot Outcomes Study (COOLXENON3 Study)

This study examines the effect of inhaled xenon gas in the treatment of newborn infants with hypoxic-ischemic encephalopathy (HIE) in combination with cooling, which is the standard treatment for this condition. The hypothesis is that the xenon + cooling combination will produce better neuroprotection than the standard treatment of cooling alone.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

50

Phase

  • Phase 2

Contacts and Locations

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

Study Locations

  • United Kingdom
      • Bristol, United Kingdom, BS2 8EG
        • St Michael's Hospital
      • London, United Kingdom, W12 0HS
        • Imperial College / Hammersmith Hospital

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

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Infants will be eligible for for the trial if the St Michael's hospital standard inclusion criteria for cooling and additional inclusion criteria for xenon administration are met.

St Michael's hospital standard inclusion criteria for standard hypothermia treatment of 72 hrs:

A: Neonates born at greater than 36 weeks gestation (estimated or clinical assessment) with at least ONE of the following:

  1. Apgar score of ≤5 at ten minutes after birth
  2. Continued need for resuscitation, including tracheal or mask ventilation, at ten minutes after birth
  3. Acidosis, defined as either umbilical cord pH or any arterial, venous or capillary pH within 60 minutes of birth less < 7.00
  4. Base deficit ≥16 mmol/L in umbilical cord blood sample or any blood sample within 60 minutes of birth (arterial or venous blood).

If the infant meets criterion A then assess for neurological abnormality using criterion B and C (by trained personnel):

B: Moderate or Severe encephalopathy as evidenced by any of the following:

  1. Altered state of consciousness (reduced or absent responses or pathological irritability and hyper responsive and at least ONE or more of the following:
  2. Hypotonia
  3. Abnormal reflexes including oculomotor or pupillary abnormalities
  4. Absent or weak suck
  5. Clinical seizures, as recorded by trained personnel

And

C: At least 30 minutes duration of amplitude-integrated electroencephalography (aEEG) recording that shows abnormal background aEEG activity. The decision to cool is based on the worst 30 min section of the aEEG, not the best [35] or seizures (clinical or electrical) thus meeting ONE of the following:

  1. Normal background with some (> 5 min) electrical seizure activity
  2. Moderately abnormal activity (upper margin of trace >10μV and lower margin <5μV)
  3. Suppressed activity (upper margin of trace <10μV and lower margin of trace <5μV)
  4. Definite seizure activity

Additional inclusion criteria for xenon:

Before being considered for additional inhaled xenon therapy via the breathing gas mixture, the infant would need to meet further additional entry criteria (all must be met):

  1. Intubated, ventilated, sedated, being cooled
  2. ≤ 5 hours old
  3. Any seizures under control
  4. Weight > 2nd centile for gestational age
  5. Stable cardiovascular parameters; Mean arterial pressure >40mmHg.
  6. Oxygen requirement via mechanical ventilator ≤ 40%.
  7. Positive End Expiratory Pressure (PEEP) requirement ≤ 8cm H2O
  8. Arterial (preferable)/capillary/venous pCO2 within acceptable range (<7kPa)
  9. Postnatal age ≤ 5 hours
  10. Absence of major congenital abnormalities, imperforate anus and in particular any bowel obstruction, congenital abnormalities suggestive of chromosomal anomaly or other syndromes that include brain dysgenesis. Congenital syndromes affecting the brain should be excluded when diagnosed.

Exclusion criteria for cooling in the CoolXenon3 study:

  1. Infants expected to be greater than 3 hours of age at the time of starting cooling treatment.
  2. Futility. Where prognosis is considered to be hopeless e.g. no cardiac output for 20 minutes.

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: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 72h cooling + 18h xenon inhalation
Babies in poor condition at birth and referred to our neonatal unit for standard therapy of cooling to 33.5 degree C body temperature will be randomised to receive xenon gas at 50% concentration for 18 hours
Drug: Xenon gas
Inhalation via endotracheal tube of 50% xenon for 18 hours, including during transport for outborn babies, starting within 5 hours after birth.
Other Names:
  • LENOXe
Other: Whole body cooling
Cooling of baby to reduce rectal temperature to 33.5 degree Centigrade(standard treatment), including during transport for outborn babies, starting within 3 hours after birth.
Other Names:
  • Therapeutic hypothermia
Active Comparator: Standard 72 h whole body cooling therapy
Whole body cooling therapy to rectal temperature of 33.5 degree Centigrade (standard therapy)
Other: Whole body cooling
Cooling of baby to reduce rectal temperature to 33.5 degree Centigrade(standard treatment), including during transport for outborn babies, starting within 3 hours after birth.
Other Names:
  • Therapeutic hypothermia

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Death and moderate or severe disability - Bayley III neurodevelopmental outcome score
Time Frame: 18 months of age
Cognition, language and motor scores, hearing and vision
18 months of age

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Brain MRI
Time Frame: Before hospital discharge, within 2 weeks of birth
Magnetic Resonance Imaging findings at less than 2 weeks of age
Before hospital discharge, within 2 weeks of birth
Amplitude Integrated Electroencephalogram (aEEG) grading
Time Frame: Before hospital discharge, usually within 1 week of birth
Number of hours after birth when aEEG voltage has reached a normal or discontinuous normal pattern
Before hospital discharge, usually within 1 week of birth

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of normal infants
Time Frame: 18-24 months
Bayley III composite score ≥ 85 and no neurosensory disability as described above
18-24 months

Collaborators and Investigators

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

Sponsor

University Hospitals Bristol and Weston NHS Foundation Trust

Collaborators

University of Bristol

Investigators

  • Principal Investigator: Marianne Thoresen, Professor, University of Bristol

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)

March 1, 2014

Primary Completion (Actual)

October 7, 2019

Study Completion (Actual)

April 15, 2020

Study Registration Dates

First Submitted

February 21, 2014

First Submitted That Met QC Criteria

February 24, 2014

First Posted (Estimate)

February 25, 2014

Study Record Updates

Last Update Posted (Actual)

January 5, 2023

Last Update Submitted That Met QC Criteria

January 3, 2023

Last Verified

January 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CH/2013/4414
  • 2013-004478-80 (EudraCT Number)
  • 13/SW/0300 (Other Identifier: NRES Committee South West)
  • CI/2013/0050 (Other Identifier: MHRA Devices)
  • 12893/0235/001-0001 (Other Identifier: MHRA Medicines)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

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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