Hypoxic Ischaemic EncephalopathyPhase 1/2CoolXenon2NCT01545271
Xenon and Cooling Therapy in Babies at High Risk of Brain Injury Following Poor Condition at Birth
A Phase 1/2 study testing xenon gas and Whole body cooling in people with Hypoxic Ischaemic Encephalopathy, run by University Hospitals Bristol and Weston NHS Foundation Trust at 1 site in United Kingdom.
Trial summary
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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Hypoxic Ischaemic Encephalopathy
- What is being tested?
- xenon gas and Whole body cooling
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- May 2012to Mar 2015
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
None listed.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Xenon and Cooling Therapy in Babies at High Risk of Brain Injury Following Poor Condition at Birth: A Randomised Pilot 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.
- Conditions
- Hypoxic Ischaemic Encephalopathy
- Being tested
- xenon gas, Whole body cooling
- Keywords
- Xenon, Hypothermia, Hypoxic Ischemic Encephalopathy, Newborn, Term, Neuroprotection, Cooling, HIE
- Medical subject headings
- Hypoxia-Ischemia, Brain, Hypothermia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
xenon gasDrug
Also called LENOXe
Inhalation via endotracheal tube of 50% xenon for 18 hours, including during transport for outborn babies, starting within 5 hours after birth.
Whole body coolingDevice
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.
| Study group | Role | What they receive |
|---|---|---|
| 72h cooling + 18h xenon inhalation | Experimental | 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 Receives: Drug: xenon gas; Device: Whole body cooling |
| Standard 72 h whole body cooling therapy | Active comparator | Whole body cooling therapy to rectal temperature of 33.5 degree Centigrade (standard therapy) Receives: Device: Whole body cooling |
What is being measured
The primary outcome is the main question the study is designed to answer.
Death and moderate or severe disability - Bayley III
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.
Measured: at 18 months of age
Secondary outcomes (2)
Brain MRI
Magnetic Resonance Imaging findings at less than 2 weeks of age
Measured: less than 2 weeks of age
Amplitude Integrated Electroencephalogram (aEEG) grading
Number of hours after birth when aEEG voltage has reached a normal or discontinuous normal pattern
Measured: Before hospital discharge; usually within one week of birth
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Mar 2012 (estimated)
- Study startMay 2012
- Primary completionOct 2013
- Study completionMar 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Hypoxic Ischaemic EncephalopathyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospitals Bristol and Weston NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Collaborators
- University of Bristol
- Responsible party
- Sponsor
- Investigators
- Marianne Thoresen, Professor, Principal investigator, University of Bristol
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01545271
- Sponsor's protocol ID
- CH/2011/3799
- Other IDs
- 2011-005397-34, 12/SW/0010
- Acronym
- CoolXenon2
- Status last verified
- Dec 2022
- First submitted
- 29 Feb 2012
- Last updated
- 15 Dec 2022
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
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.
PubMed 19608817Hobbs 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.
PubMed 18309163Thoresen 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.
PubMed 19142190Chakkarapani 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.
PubMed 20658563Chakkarapani 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.
PubMed 22160201Dingley 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.
PubMed 25794112Shankaran 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.
PubMed 24524452
Study at a glance
From the registry record, last updated by the sponsor on 15 Dec 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Xenon and Cooling Therapy in Babies at High Risk of Brain Injury Following Poor Condition at Birth: A Randomised Pilot Study
- ClinicalTrials.gov ID
- NCT01545271
- Acronym / sponsor ID
- CoolXenon2 / CH/2011/3799
- Conditions
- Hypoxic Ischaemic Encephalopathy
- Keywords
- Xenon, Hypothermia, Hypoxic Ischemic Encephalopathy, Newborn, Term, Neuroprotection, Cooling, HIE
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- University Hospitals Bristol and Weston NHS Foundation TrustUniversity, hospital or other
- Collaborators
- University of Bristol
- Study start
- May 2012
- Primary completion
- Oct 2013 (actual)
- Study completion
- Mar 2015 (actual)
- First posted
- 6 Mar 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 72h cooling + 18h xenon inhalation | Experimental | Drug: xenon gas, Device: Whole body coolingBabies 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 |
| Standard 72 h whole body cooling therapy | Active comparator | Device: Whole body coolingWhole body cooling therapy to rectal temperature of 33.5 degree Centigrade (standard therapy) |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (0 listed)
Key exclusion criteria (2 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| xenon gasAlso: LENOXeInhalation via endotracheal tube of 50% xenon for 18 hours, including during transport for outborn babies, starting within 5 hours after birth. | Drug | 72h cooling + 18h xenon inhalation |
| Whole body coolingCooling 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. | Device | 72h cooling + 18h xenon inhalation, Standard 72 h whole body cooling therapy |
Primary outcome
Death and moderate or severe disability - Bayley III
Time frame: at 18 months of age
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.
2 secondary outcomes
Brain MRI
Time frame: less than 2 weeks of age
Amplitude Integrated Electroencephalogram (aEEG) grading
Time frame: Before hospital discharge; usually within one week of birth
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Dec 2022.
- Background: PubMed 19608817Chakkarapani 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.
- Background: PubMed 18309163Hobbs 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.
- Background: PubMed 19142190Thoresen 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.
- Background: PubMed 20658563Chakkarapani 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.
- Background: PubMed 22160201Chakkarapani 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.
- Derived from this study: PubMed 25794112Dingley 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.
- Derived from this study: PubMed 24524452Shankaran 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Marianne Thoresen, Professor principal investigator
University of Bristol
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing xenon gas and Whole body cooling in people with Hypoxic Ischaemic Encephalopathy, run by University Hospitals Bristol and Weston NHS Foundation Trust at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 0 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Dec 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Death and moderate or severe disability - Bayley III (time frame: at 18 months of age). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01545271, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Dec 2022.