Xenon and Cooling Therapy in Babies at High Risk of Brain Injury Following Poor Condition at Birth (CoolXenon2)

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2013 by United Bristol Healthcare NHS Trust
Sponsor:
Collaborator:
University of Bristol
Information provided by (Responsible Party):
United Bristol Healthcare NHS Trust
ClinicalTrials.gov Identifier:
NCT01545271
First received: February 29, 2012
Last updated: January 31, 2013
Last verified: January 2013
  Purpose

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.


Condition Intervention Phase
Hypoxic Ischaemic Encephalopathy
Drug: xenon gas
Device: Full body cooling
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Xenon and Cooling Therapy in Babies at High Risk of Brain Injury Following Poor Condition at Birth: Randomised Pilot Study

Resource links provided by NLM:


Further study details as provided by United Bristol Healthcare NHS Trust:

Primary Outcome Measures:
  • Amplitude Integrated Electroencephalogram (aEEG) grading [ Designated as safety issue: No ]
    Number of hours after birth when aEEG voltage has reached a normal or discontinuous normal pattern

  • Brain MRI [ Time Frame: less than 2 weeks of age ] [ Designated as safety issue: No ]
    Magnetic Resonance Imaging findings at less than 2 weeks of age


Estimated Enrollment: 24
Study Start Date: May 2012
Estimated Study Completion Date: April 2014
Estimated Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Drug: xenon gas
Inhalation via endotracheal tube of 50% xenon for 18 hours
Active Comparator: Standard 72 h whole body cooling therapy
Whole body cooling therapy to rectal temperature of 33.5 degree Centigrade (standard therapy)
Device: Full body cooling
Cooling of baby to reduce rectal temperature to 33.5 degree Centigrade(standard treatment)

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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:

  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

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):

  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 for cooling in the CoolXenon2 study

  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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01545271

Contacts
Contact: Marianne Thoresen, Professor +44117 342 5226 carol.s.bond@bristol.ac.uk
Contact: Carol Bond +44117 342 5226 carol.s.bond@bristol.ac.uk

Locations
United Kingdom
St Michael's Hospital Recruiting
Bristol, Avon, United Kingdom, BS2 8EG
Sponsors and Collaborators
United Bristol Healthcare NHS Trust
University of Bristol
Investigators
Principal Investigator: Marianne Thoresen, Professor University of Bristol
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: United Bristol Healthcare NHS Trust
ClinicalTrials.gov Identifier: NCT01545271     History of Changes
Other Study ID Numbers: CH/2011/3799, 2011-005397-34, 12/SW/0010
Study First Received: February 29, 2012
Last Updated: January 31, 2013
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
United Kingdom: National Health Service
United Kingdom: Research Ethics Committee

Keywords provided by United Bristol Healthcare NHS Trust:
Xenon
Hypothermia
Hypoxic Ischemic Encephalopathy
Newborn
Term
Neuroprotection
Cooling
HIE

Additional relevant MeSH terms:
Brain Ischemia
Ischemia
Brain Diseases
Brain Injuries
Hypoxia-Ischemia, Brain
Wounds and Injuries
Cerebrovascular Disorders
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Pathologic Processes
Craniocerebral Trauma
Trauma, Nervous System
Hypoxia, Brain
Xenon
Anesthetics, Inhalation
Anesthetics, General
Anesthetics
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 01, 2014