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

NCT ID: NCT01545271

Last Updated: 2022-12-15

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

32 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-05-31

Study Completion Date

2015-03-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Hypoxic Ischaemic Encephalopathy

Keywords

Explore important study keywords that can help with search, categorization, and topic discovery.

Xenon Hypothermia Hypoxic Ischemic Encephalopathy Newborn Term Neuroprotection Cooling HIE

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

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

Group Type EXPERIMENTAL

xenon gas

Intervention Type DRUG

Inhalation via endotracheal tube of 50% xenon for 18 hours, including during transport for outborn babies, starting within 5 hours after birth.

Whole body cooling

Intervention Type DEVICE

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.

Standard 72 h whole body cooling therapy

Whole body cooling therapy to rectal temperature of 33.5 degree Centigrade (standard therapy)

Group Type ACTIVE_COMPARATOR

Whole body cooling

Intervention Type DEVICE

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.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

xenon gas

Inhalation via endotracheal tube of 50% xenon for 18 hours, including during transport for outborn babies, starting within 5 hours after birth.

Intervention Type DRUG

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.

Intervention Type DEVICE

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

LENOXe

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

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


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 ≤ 6cm H2O
8. Arterial pCO2 within acceptable range (\<7kPa)
9. 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

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.
Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

University of Bristol

OTHER

Sponsor Role collaborator

University Hospitals Bristol and Weston NHS Foundation Trust

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Marianne Thoresen, Professor

Role: PRINCIPAL_INVESTIGATOR

University of Bristol

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

St Michael's Hospital

Bristol, Avon, United Kingdom

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United Kingdom

References

Explore related publications, articles, or registry entries linked to this study.

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.

Reference Type BACKGROUND
PMID: 19608817 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18309163 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19142190 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20658563 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22160201 (View on PubMed)

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.

Reference Type DERIVED
PMID: 25794112 (View on PubMed)

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.

Reference Type DERIVED
PMID: 24524452 (View on PubMed)

Provided Documents

Download supplemental materials such as informed consent forms, study protocols, or participant manuals.

Document Type: Study Protocol

View Document

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

2011-005397-34

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

12/SW/0010

Identifier Type: OTHER

Identifier Source: secondary_id

CH/2011/3799

Identifier Type: -

Identifier Source: org_study_id