- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01545271
Xenon and Cooling Therapy in Babies at High Risk of Brain Injury Following Poor Condition at Birth (CoolXenon2)
Xenon and Cooling Therapy in Babies at High Risk of Brain Injury Following Poor Condition at Birth: A Randomised Pilot Study
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
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Avon
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Bristol, Avon, United Kingdom, BS2 8EG
- St Michael's Hospital
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Child
- Adult
- Older Adult
Accepts Healthy Volunteers
Genders Eligible for Study
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:
- Apgar score of ≤5 at ten minutes after birth
- Continued need for resuscitation, including tracheal or mask ventilation, at ten minutes after birth
- Acidosis, defined as either umbilical cord pH or any arterial, venous or capillary pH within 60 minutes of birth less < 7.00
- 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:
- Altered state of consciousness (reduced or absent responses or pathological irritability and hyper responsive and at least ONE or more of the following:
- Hypotonia
- Abnormal reflexes including oculomotor or pupillary abnormalities
- Absent or weak suck
- 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:
- Normal background with some (> 5 min) electrical seizure activity
- Moderately abnormal activity (upper margin of trace >10μV and lower margin <5μV)
- Suppressed activity (upper margin of trace <10μV and lower margin of trace <5μV)
- 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):
- Intubated, ventilated, sedated, being cooled
- ≤ 5 hours old
- Any seizures under control
- Weight > 2nd centile for gestational age
- Stable cardiovascular parameters; Mean arterial pressure >40mmHg.
- Oxygen requirement via mechanical ventilator ≤ 40%.
- Positive End Expiratory Pressure (PEEP) requirement ≤ 6cm H2O
- Arterial pCO2 within acceptable range (<7kPa)
- 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 CoolXenon2 study
- Infants expected to be greater than 3 hours of age at the time of starting cooling treatment.
- Futility. Where prognosis is considered to be hopeless e.g. no cardiac output for 20 minutes.
Study Plan
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
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Inhalation via endotracheal tube of 50% xenon for 18 hours, including during transport for outborn babies, starting within 5 hours after birth.
Other Names:
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.
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Active Comparator: Standard 72 h whole body cooling therapy
Whole body cooling therapy to rectal temperature of 33.5 degree Centigrade (standard therapy)
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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.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Death and moderate or severe disability - Bayley III
Time Frame: at 18 months of age
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Bayley Scales of Infant and Toddler Development III (Bayley III) has three domains: cognition, language and motor skills.
Each domain is based on a series of examinations of different severity.
The lower cut off level is 55 for cognition, 47 for language and 46 for motor.
The upper value can be 145.
Assessment of hearing and vision: severe hearing loss defined as inability to hear without amplification; severe visual loss defined as being unable to move independently.
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at 18 months of age
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Brain MRI
Time Frame: less than 2 weeks of age
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Magnetic Resonance Imaging findings at less than 2 weeks of age
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less than 2 weeks of age
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Amplitude Integrated Electroencephalogram (aEEG) grading
Time Frame: Before hospital discharge; usually within one week of birth
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Number of hours after birth when aEEG voltage has reached a normal or discontinuous normal pattern
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Before hospital discharge; usually within one week of birth
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Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of normal infants
Time Frame: 18-24 months
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Bayley III composite score ≥ 85 and no neurosensory disability as described above
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18-24 months
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Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Marianne Thoresen, Professor, University of Bristol
Publications and helpful links
General Publications
- Chakkarapani E, Thoresen M, Hobbs CE, Aquilina K, Liu X, Dingley J. A closed-circuit neonatal xenon delivery system: a technical and practical neuroprotection feasibility study in newborn pigs. Anesth Analg. 2009 Aug;109(2):451-60. doi: 10.1213/ane.0b013e3181aa9550.
- Hobbs C, Thoresen M, Tucker A, Aquilina K, Chakkarapani E, Dingley J. Xenon and hypothermia combine additively, offering long-term functional and histopathologic neuroprotection after neonatal hypoxia/ischemia. Stroke. 2008 Apr;39(4):1307-13. doi: 10.1161/STROKEAHA.107.499822. Epub 2008 Feb 28.
- Thoresen M, Hobbs CE, Wood T, Chakkarapani E, Dingley J. Cooling combined with immediate or delayed xenon inhalation provides equivalent long-term neuroprotection after neonatal hypoxia-ischemia. J Cereb Blood Flow Metab. 2009 Apr;29(4):707-14. doi: 10.1038/jcbfm.2008.163. Epub 2009 Jan 14.
- Chakkarapani E, Dingley J, Liu X, Hoque N, Aquilina K, Porter H, Thoresen M. Xenon enhances hypothermic neuroprotection in asphyxiated newborn pigs. Ann Neurol. 2010 Sep;68(3):330-41. doi: 10.1002/ana.22016.
- Chakkarapani E, Thoresen M, Liu X, Walloe L, Dingley J. Xenon offers stable haemodynamics independent of induced hypothermia after hypoxia-ischaemia in newborn pigs. Intensive Care Med. 2012 Feb;38(2):316-23. doi: 10.1007/s00134-011-2442-7. Epub 2011 Dec 13.
- Dingley J, Liu X, Gill H, Smit E, Sabir H, Tooley J, Chakkarapani E, Windsor D, Thoresen M. The feasibility of using a portable xenon delivery device to permit earlier xenon ventilation with therapeutic cooling of neonates during ambulance retrieval. Anesth Analg. 2015 Jun;120(6):1331-6. doi: 10.1213/ANE.0000000000000693.
- Shankaran S. Outcomes of hypoxic-ischemic encephalopathy in neonates treated with hypothermia. Clin Perinatol. 2014 Mar;41(1):149-59. doi: 10.1016/j.clp.2013.10.008.
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Vascular Diseases
- Cerebrovascular Disorders
- Central Nervous System Diseases
- Nervous System Diseases
- Wounds and Injuries
- Craniocerebral Trauma
- Trauma, Nervous System
- Signs and Symptoms, Respiratory
- Hypoxia
- Hypoxia, Brain
- Brain Ischemia
- Brain Injuries
- Brain Diseases
- Hypoxia-Ischemia, Brain
- Physiological Effects of Drugs
- Central Nervous System Depressants
- Anesthetics, General
- Anesthetics
- Anesthetics, Inhalation
- Xenon
Other Study ID Numbers
- CH/2011/3799
- 2011-005397-34 (EudraCT Number)
- 12/SW/0010 (Other Identifier: NRES Committee South West)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
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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