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

NCT02071394 | Completed Phase 2 DMC

• 5 other identifiers: CH/2013/44142013-004478-8013/SW/0300CI/2013/005012893/0235/001-0001
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 2

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; Neonate; Term; Neuroprotection; Cooling; HIE

Outcome Measures

Primary Outcomes (1)

• Death and moderate or severe disability - Bayley III neurodevelopmental outcome score

  Cognition, language and motor scores, hearing and vision

  18 months of age

Secondary Outcomes (2)

• Brain MRI

  Before hospital discharge, within 2 weeks of birth

• Amplitude Integrated Electroencephalogram (aEEG) grading

  Before hospital discharge, usually within 1 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; Other: 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)

Other: 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 OTHER

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.

Also known as: Therapeutic hypothermia

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 (2)

St Michael's Hospital

Bristol, BS2 8EG, United Kingdom

Location

Imperial College / Hammersmith Hospital

London, W12 0HS, 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, Tooley J, Liu X, Scull-Brown E, Elstad M, Chakkarapani E, Sabir H, Thoresen M. Xenon ventilation during therapeutic hypothermia in neonatal encephalopathy: a feasibility study. Pediatrics. 2014 May;133(5):809-18. doi: 10.1542/peds.2013-0787.

  PMID: 24777219 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 BACKGROUND

MeSH Terms

Conditions

Hypoxia-Ischemia, Brain; Hypothermia

Interventions

Lasers, Gas; Hypothermia, Induced

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; Cryotherapy; Therapeutics

Study Officials

• Marianne Thoresen, Professor

  University of Bristol

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 21, 2014
• First Posted: February 25, 2014
• Study Start: March 1, 2014
• Primary Completion: October 7, 2019
• Study Completion: April 15, 2020
• Last Updated: January 5, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will not share

Locations

GB (2)