Outcome After 24 Months of Participants in the TOBY Xenon Study

Study Overview
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Brief Summary
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The objective of this study is to document the outcome at 2-3 years of age of participants of the TOBY Xe trial, to provide preliminary information about the later clinical effects of treatment with Xenon gas combined with moderate hypothermia following perinatal asphyxia. The TOBY Xe trial was a randomised controlled trial of inhaled xenon gas combined with hypothermia for the treatment of perinatal asphyxia. The trial primary outcome was changes on magnetic resonance parameters examined prior to discharge from hospital. Continuing clinical follow-up of trial participants is important following any therapeutic trial and is essential in early phase trials where information on the clinical effects of the intervention are lacking. Therefore, we have set up this study to determine the major clinical and neurological outcomes of participants of the TOBY Xe trial and to determine whether the magnetic resonance parameters in that trial are qualified to predict outcome following neural rescue therapy. This information is necessary for planning further studies of this intervention.

Official Title
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Neurological Outcome After 24 Months of Age Following Treatment With Xenon Combined With Moderate Hypothermia After Perinatal Asphyxia

Conditions
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Perinatal Asphyxia, Encephalopathy

Intervention / Treatment
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* Drug: Xenon


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Surviving participants in the TOBY Xenon study Exclusion Criteria: Lack of consent to participate

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 3 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Standard care with moderate hypothermia<br>Surviving children allocated to standard care with moderate hypothermia in the TOBY-Xe trial | |
| 30% Xenon for 24 hours combined with moderate hypothermia<br>Surviving children allocated to inhaled xenon combined with moderate hypothermia in the TOBY-Xe trial | Drug: Xenon<br>* Inhaled xenon gas given via purposely designed ventilator<br>* Other names: Lenoxe;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Scores on Bayley scales of infant and toddler development | Composite scores of the Cognitive, Language and Motor scales scaled to a metric, with a mean of 100, standard deviation of 15, and range of 40 to 160 | at 2-3 years of age | 
| Relation between magnetic resonance markers and neurodevelopmental outcome | Peak area Lactate/N Acetyl Aspartate ratio on magnetic resonance spectroscopy and fractional anisotropy on diffusion tensor magnetic resonance imaging | at 2-3 years of age | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Grade of disability | The grade of disability, categorised as mild disability (a Cognitive score of 70 to 84, level 1 gross motor function [is able to walk independently but may have some gait abnormalities], or abnormality in one or both eyes with normal or nearly normal vision), moderate disability (a Cognitive scale score of 56 to 69, level 2 or 3 gross motor function [has minimal ability to perform gross motor skills or requires assistance with walking], or moderately reduced vision), or severe disability (a Cognitive scale score of 55 (the minimum score on the Bayley Cognitive scale), level 4 or 5 gross motor function [needs adaptive seating or has severely limited mobility], or no useful vision). | At 2-3 years of age |