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

NCT01545271 | Completed Phase 1 DMC

• 3 other identifiers: CH/2011/37992011-005397-3412/SW/0010
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief 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. The hypothesis is that the xenon + cooling combination will produce better neuroprotection than the standard treatment of cooling alone.

Conditions

Hypoxic Ischaemic Encephalopathy

Keywords

Xenon; Hypothermia; Hypoxic Ischemic Encephalopathy; Newborn; Term; Neuroprotection; Cooling; HIE

Outcome Measures

Primary Outcomes (1)

• 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.

  at 18 months of age

Secondary Outcomes (2)

• Brain MRI

  less than 2 weeks of age

• Amplitude Integrated Electroencephalogram (aEEG) grading

  Before hospital discharge; usually within one week of birth

Other Outcomes (1)

• Number of normal infants

  18-24 months

Study Arms (2)

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

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)

Device: Whole body cooling

Interventions

xenon gas DRUG

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

Also known as: LENOXe

72h cooling + 18h xenon inhalation

Whole body cooling 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.

72h cooling + 18h xenon inhalation; Standard 72 h whole body cooling therapy

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University Hospitals Bristol and Weston NHS Foundation Trust: lead
• University of Bristol: collaborator

Study Sites (1)

St Michael's Hospital

Bristol, Avon, BS2 8EG, United Kingdom

Location

Related Publications (7)

• 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.

  PMID: 19608817 BACKGROUND

• 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.

  PMID: 18309163 BACKGROUND

• 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.

  PMID: 19142190 BACKGROUND

• 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.

  PMID: 20658563 BACKGROUND

• 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.

  PMID: 22160201 BACKGROUND

• 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.

  PMID: 25794112 DERIVED

• 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.

  PMID: 24524452 DERIVED

MeSH Terms

Conditions

Hypoxia-Ischemia, Brain; Hypothermia

Interventions

Lasers, Gas

Condition Hierarchy (Ancestors)

Brain Ischemia; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Hypoxia, Brain; Vascular Diseases; Cardiovascular Diseases; Hypoxia; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Body Temperature Changes

Intervention Hierarchy (Ancestors)

Lasers; Optical Devices; Equipment and Supplies; Radiation Equipment and Supplies

Study Officials

• Marianne Thoresen, Professor

  University of Bristol

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 29, 2012
• First Posted: March 6, 2012
• Study Start: May 1, 2012
• Primary Completion: October 1, 2013
• Study Completion: March 1, 2015
• Last Updated: December 15, 2022

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)