Trial Outcomes & Findings for Neuroprotective Effects of Hypothermia Combined With Inhaled Xenon Following Perinatal Asphyxia (NCT NCT00934700)

Results Overview

Cerebral Lac/NAA ratio measured by magnetic resonance spectroscopy in patents

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

92 participants

Primary outcome timeframe

10 days

Results posted on

2022-04-21

Participant Flow

Participant milestones

Participant milestones
Measure	Hypothermia and Standard Intensive Care 72 hours of whole body cooling to 33.5 rectal and standard intensive care	Combination of Hypothermia and Xenon Combination of 72 hours of whole body cooling to 33.5 rectal and 30% Xenon gas inhaled for 24 hours
Overall Study STARTED	46	46
Overall Study COMPLETED	34	33
Overall Study NOT COMPLETED	12	13

Reasons for withdrawal

Reasons for withdrawal
Measure	Hypothermia and Standard Intensive Care 72 hours of whole body cooling to 33.5 rectal and standard intensive care	Combination of Hypothermia and Xenon Combination of 72 hours of whole body cooling to 33.5 rectal and 30% Xenon gas inhaled for 24 hours
Overall Study missing scan	9	5
Overall Study Death	3	8

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Combination of Hypothermia and Xenon n=46 Participants Combination of whole body cooling to 33.5 rectal and 30% Xenon gas inhaled for 24 hours	Hypothermia and Standard Intensive Care n=46 Participants 72 hours of whole body cooling to 33.5 rectal and standard intensive care	Total n=92 Participants Total of all reporting groups
Age, Continuous	39.8 weeks, gestation STANDARD_DEVIATION 1.7 • n=46 Participants	39.8 weeks, gestation STANDARD_DEVIATION 1.3 • n=46 Participants	39.8 weeks, gestation STANDARD_DEVIATION 1.5 • n=92 Participants
Sex: Female, Male Female	20 Participants n=46 Participants	25 Participants n=46 Participants	45 Participants n=92 Participants
Sex: Female, Male Male	26 Participants n=46 Participants	21 Participants n=46 Participants	47 Participants n=92 Participants
Race and Ethnicity Not Collected	—	—	0 Participants Race and Ethnicity were not collected from any participant.
Region of Enrollment United Kingdom	46 participants n=46 Participants	46 participants n=46 Participants	92 participants n=92 Participants

PRIMARY outcome

Timeframe: 10 days

Cerebral Lac/NAA ratio measured by magnetic resonance spectroscopy in patents

Outcome measures

Outcome measures
Measure	Combination of Hypothermia and Xenon n=33 Participants Combination of whole body cooling to 33.5 rectal and hypothermia and 30% Xenon gas inhaled for 24 hours	Hypothermia and Standard Intensive Care n=34 Participants 72 hours of whole body cooling to 33.5 rectal and standard intensive care
Lactate (Lac) / N Acetyl Aspartate (NAA) Ratio on Magnetic Resonance Spectroscopy	0.25 ratio Geometric Coefficient of Variation 1.30	0.28 ratio Geometric Coefficient of Variation 1.45

PRIMARY outcome

Timeframe: 10 days

Fractional anisotropy (FA) is a measure of tissue integrity in white matter tracts measured by diffusion tensor MRI, and it has been used in work in animals to assess potential neuroprotectants and can be used to predict subsequent neurological outcomes after birth asphyxia, including in infants treated with moderate hypothermia. It is a scalar value between 0-1 that describe anisotropy of a diffusion process. A value of zero means that diffusion is unrestricted (or equally restricted) in all directions. A value of one means that diffusion occurs only along one axis and is fully restricted along all other directions" or similar. Fractional anisotropy data were extracted froma mask of the posterior limb of the internal capsule via tract-based spatial statistics. \*Coefficient of variation=√(exp(var)-1), where var is the variance on the log scale

Outcome measures

Outcome measures
Measure	Combination of Hypothermia and Xenon n=30 Participants Combination of whole body cooling to 33.5 rectal and hypothermia and 30% Xenon gas inhaled for 24 hours	Hypothermia and Standard Intensive Care n=33 Participants 72 hours of whole body cooling to 33.5 rectal and standard intensive care
Cerebral Fractional Anisotropy Measured by Diffusion Weighted Magnetic Resonance Imaging	0.40 units on a scale Standard Deviation 0.05	0.40 units on a scale Standard Deviation 0.05

SECONDARY outcome

Timeframe: At discharge from hospital

Population: Infants survivors at time of hospital discharge

Amiel Tison neurological assessment at discharge from hospital. Amiel Tison evaluation was developed to detect transient and permanent abnormalities in an infant's neuromotor development. Its main focus is to examine active and passive muscle tone.

Outcome measures

Outcome measures
Measure	Combination of Hypothermia and Xenon n=35 Participants Combination of whole body cooling to 33.5 rectal and hypothermia and 30% Xenon gas inhaled for 24 hours	Hypothermia and Standard Intensive Care n=37 Participants 72 hours of whole body cooling to 33.5 rectal and standard intensive care
Amiel Tison Evaluation at Hospital Discharge Normal or mildly abnormal	30 Participants	29 Participants
Amiel Tison Evaluation at Hospital Discharge Moderately abnormal	3 Participants	7 Participants
Amiel Tison Evaluation at Hospital Discharge Very abnormal	2 Participants	1 Participants

Adverse Events

Combination of Hypothermia and Xenon

Serious events: 0 serious events

Other events: 2 other events

Deaths: 11 deaths

Hypothermia and Standard Intensive Care

Serious events: 0 serious events

Other events: 0 other events

Deaths: 9 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Combination of Hypothermia and Xenon n=46 participants at risk Combination of whole body cooling to 33.5 rectal and 30% Xenon gas inhaled for 24 hours	Hypothermia and Standard Intensive Care n=46 participants at risk 72 hours of whole body cooling to 33.5 rectal and standard intensive care
Skin and subcutaneous tissue disorders Subcutaneous fat necrosis	2.2% 1/46 • Number of events 1 • 10days	0.00% 0/46 • 10days
General disorders Transient desaturation during MRI scan	2.2% 1/46 • Number of events 1 • 10days	0.00% 0/46 • 10days

Additional Information

Research Integrity Officer

Imperial College London

Phone: +44 020 7594 1872

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place