Neonatal hypoxia-ischaemia (HI). There is no exact MedDRA term for this. The closest MedDRA terms matching this are neonatal asphyxia and neonatal hypoxia. MedDRA version: 14.1 Level: PT Classification code 10050081 Term: Neonatal hypoxia System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders MedDRA version: 14.1 Level: HLT Clas
Conditions
Interventions
Trade Name: LENOXe
Product Name: LENOXe
Pharmaceutical Form: Inhalation gas
INN or Proposed INN: Xenon
Concentration unit: % (V/V) perce
Sponsors
University Hospital Bristol NHS Foundation Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion Criteria Patients meeting the following criteria will be considered eligible for the study: Infants will be eligible for inclusion in this study if the St Michael???s hospital standard inclusion criteria for cooling are met and additional inclusion criteria for xenon administration are met. St Michael???s hospital standard inclusion criteria for cooling Standard Hypothermia Treatment Criteria for 72 hrs of cooling ??? all of criteria A, B, and C. A Infants > 36.0 weeks gestation (clinical assessment) with at least ONE of the following: 1 Apgar score of 10µV and lower margin 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 the accepted range (4.0-6.5 kPa) 9) Postnatal age <5 hours 10) Absence of major congenital abnormalities, imperforate anus and in particular any bowel obstruction, congenital abnormalities
Exclusion criteria
Exclusion criteria: Exclusion Criteria Exclusion criteria for cooling 1. Infants expected to be greater than 5 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. Additional exclusion criteria for xenon Failure to meet any of the additional inclusion criteria for xenon listed in section 5.1. Patients meeting the following criteria are NOT eligible for the study: Presence of any 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. (Neonates with congenital syndromes affecting the brain should be excluded when diagnosed).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary Objective: This is a randomised two group pilot study comparing; i) xenon inhalation for 18 hours in combination with whole body cooling to 33.5 °C for 3 days, to ii) the established treatment of cooling the body down to 33.5 °C for 3 days. This will be applied in term newborn babies who are at moderate or high risk of brain injury following poor condition around the time of birth. Our hypothesis is that during the first 2 weeks after birth using a combination of validated (in our own and others cohorts) early predictors of outcome we may observe an enhanced neuroprotective effect of the xenon-cooling combination over cooling alone and this will allow us to perform power calculations for a larger definitive neurological outcomes study of otherwise similar design. Outcome predictors are based on a combination of: 1) Time in hours after birth when background activity as recorded by amplitude integrated EEG (aEEG: from single channel EEG) [1] and onset of sleep ; Timepoint(s) of evaluation of this end point: The early predictors of outcome will be completed by 2 weeks of age. The neurodevelopmental follow up will be completed by 2 years of age. ; Secondary Objective: Secondary Objectives: We will monitor a number of variables before/during and after the period of xenon delivery. This group of physiological and biochemical parameters includes those recorded during our recently completed xenon+cooling feasibility/safety study in neonates and a few more are added . They are: Gas exchange: Transcutaneous oxygen saturation, end-tidal carbon dioxide concentration, blood gas data (from arterial sample), mechanical ventilation requirements (rate, peak inspiratory pressure, PEEP settings). Haemodynamic: S | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): A series of variables that are among the most relevant for evaluation of safety (see endpoints below) were examined closely in the previous 14 baby feasibility/safety study. We will continue to routinely monitor and record the same set of physiological variables in the proposed study, for a subset of data for a longer time period until after rewarming. ??? Endpoint 1 ??? defined as Mechanical ventilation and gas exchange parameters ??? The following variables will be measured before (from start cooling), during and after xenon administration (for 12h or until 12h after end of cooling hours pending which variable):Transcutaneous Oxygen saturation, end-tidal carbon dioxide concentration, blood gas data, mechanical ventilation requirements (rate, peak inspiratory pressure, inspiratory time, PEEP settings),FiO2. Average percentage xenon in inspired gas mixture (when applicable). Tracheal tube cuff pressure. ??? Endpoint 2 ??? defined as Haemodynamic parameters ??? The following variables will be measured before, during and after xenon administration: Systolic, mean and diastolic arterial pressures, Heart rate. ??? Endpoint 3 ??? defined as Inotropic drug requirements ??? These (drug, dose and duration) will be recorded before, during and after xenon administration until 12h after end of cooling. ??? Endpoint 4 ??? defined as Marker of myocardial impairment/insult The following will be recorded before and after xenon administration: Plasma levels Troponin T (marker of myocardial cell death) recorded before and after xenon administration until 12h after end of cooling: ??? Endpoint 5 ??? defined as timecourse and peak value of Markers of hepatic impairment ??? These will be recorded before and after xenon administration until 12h after end of cooling: [Alanine aminotransferase , Alka | — |
Countries
United Kingdom
Contacts
Public ContactProfessor Marianne Thoresen
University Hospitals Bristol
Outcome results
None listed