TOBY Xe

Neuroprotective effects of hypothermia combined with inhaled xenon following perinatal asphyxia.

Trial started: 2012  Trial ended: 2014 

Summary

Objectives

To assess whether the addition of xenon gas after initiation of moderate hypothermia for birth asphyxia provides further neuroprotective benefit.

Methods

A proof-of-concept, randomised, open-label, parallel-group trial conducted at four intensive-care neonatal units in the UK. Infants born at 36–43 weeks' gestation with signs of moderate to severe encephalopathy and abnormal amplitude-integrated EEG (aEEG) were randomised to receive either cooling to a rectal temperature of 33.5°C for 72 hours or cooling in combination with 30% inhaled xenon for 24 hours, started immediately after randomisation.

Outcome measures

Primary outcomes: Lactate to N-acetyl aspartate ratio in the thalamus and preserved fractional anisotropy in the posterior limb of the internal capsule, measured using magnetic resonance spectroscopy and MRI, respectively, within 15 days of birth.

Results

A total of 92 infants were enrolled, with 46 randomised to cooling alone and 46 to xenon plus cooling. Magnetic resonance assessments were undertaken in 37 infants in the cooling group and 41 in the xenon plus cooling group. There were no significant differences between the groups in lactate to N-acetyl aspartate ratio in the thalamus (geometric mean ratio 1.09, 95% confidence interval 0.90 to 1.32) or fractional anisotropy in the posterior limb of the internal capsule (mean difference ?0.01, 95% confidence interval ?0.03 to 0.02). Nine infants died in the cooling group and 11 in the xenon plus cooling group. Two adverse events were reported in the xenon group: subcutaneous fat necrosis and transient desaturation during MRI. No serious adverse events were recorded.

Conclusions

Administration of xenon within the delayed timeframe used in this trial was feasible and apparently safe, but was unlikely to enhance the neuroprotective effect of cooling after birth asphyxia.

Adapted from: Azzopardi D, Robertson NJ, Bainbridge A, et al. Moderate hypothermia within 6 h of birth plus inhaled xenon versus moderate hypothermia alone after birth asphyxia (TOBY-Xe): a proof-of-concept, open-label, randomised controlled trial. The Lancet Neurology. 2016;15(2):145–153. https://doi.org/10.1016/S1474-4422(15)00347-6. Licensed under the Creative Commons Attribution 4.0 International (CC BY 4.0) Licence (https://creativecommons.org/licenses/by/4.0/). Adapted for presentation on this website.