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| Name | Class |
|---|---|
| University College London Hospitals | OTHER |
| Guy's and St Thomas' NHS Foundation Trust | OTHER |
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This is a randomised controlled trial in newborn infants with perinatal asphyxial encephalopathy assessing whether a combination of hypothermia and inhaled xenon preserve cerebral metabolism and structure.
The study hypothesis is that: Following perinatal asphyxia treatment with a combination of hypothermia and inhaled xenon preserves cerebral metabolism and structure. Following informed parental consent, infants that continue to require endotracheal tube ventilation following resuscitation will be randomised to treatment with hypothermia only or hypothermia and xenon. All infants in both groups will be treated with hypothermia for 72 hours started within 6 hours of delivery and infants allocated to hypothermia and xenon will also receive 30% xenon (balanced with oxygen and air) for 24 hours through a purpose designed delivery system. Structured neurological examination will be done daily during the 1st week after birth and at discharge. MRS and MRI will be performed once between 4-10 days of age. MRS/MRI data analysis will be by investigators blinded to the allocated intervention.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Combination of hypothermia and xenon | Experimental | Combination of hypothermia and inhaled xenon |
|
| Hypothermia and standard intensive care | No Intervention | Hypothermia and standard intensive care |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Xenon gas | Other | 30% Xenon gas inhaled for 24 hours |
|
| Measure | Description | Time Frame |
|---|---|---|
| Lactate (Lac) / N Acetyl Aspartate (NAA) Ratio on Magnetic Resonance Spectroscopy | Cerebral Lac/NAA ratio measured by magnetic resonance spectroscopy in patents | 10 days |
| Cerebral Fractional Anisotropy Measured by Diffusion Weighted Magnetic Resonance Imaging | 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 | 10 days |
| Measure | Description | Time Frame |
|---|---|---|
| Amiel Tison Evaluation at 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. | At discharge from hospital |
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Inclusion Criteria:
Infants will be eligible for enrolment into the trial if each of the following criteria is fulfilled:
Infants 36 to 43 weeks gestation with at least one of the following:
Moderate to severe encephalopathy consisting of altered state of consciousness (reduced or absent response to stimulation) and hypotonia, and abnormal primitive reflexes (weak or absent suck or Moro response). Clinical severity of HIE will be assessed by Thompson encephalopathy score, and modified Sarnat score.
At least 30 minutes duration of amplitude integrated EEG (aEEG) recording that shows moderately abnormal or suppressed background aEEG activity or seizures
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Denis Azzopardi, MD | Imperial College London | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Imperial College Academic Healthcare Trust | London | W12 0HS | United Kingdom |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 26708675 | Result | Azzopardi D, Robertson NJ, Bainbridge A, Cady E, Charles-Edwards G, Deierl A, Fagiolo G, Franks NP, Griffiths J, Hajnal J, Juszczak E, Kapetanakis B, Linsell L, Maze M, Omar O, Strohm B, Tusor N, Edwards AD. 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. Lancet Neurol. 2016 Feb;15(2):145-153. doi: 10.1016/S1474-4422(15)00347-6. Epub 2015 Dec 19. | |
| 24524452 |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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 |
| FG001 | Hypothermia and Standard Intensive Care | 72 hours of whole body cooling to 33.5 rectal and standard intensive care |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Combination of Hypothermia and Xenon | Combination of whole body cooling to 33.5 rectal and 30% Xenon gas inhaled for 24 hours |
| BG001 | Hypothermia and Standard Intensive Care | 72 hours of whole body cooling to 33.5 rectal and standard intensive care |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Gestation at delivery in weeks |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Lactate (Lac) / N Acetyl Aspartate (NAA) Ratio on Magnetic Resonance Spectroscopy | Cerebral Lac/NAA ratio measured by magnetic resonance spectroscopy in patents | Posted | Geometric Mean | Geometric Coefficient of Variation | ratio | 10 days |
|
10days
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Combination of Hypothermia and Xenon | Combination of whole body cooling to 33.5 rectal and 30% Xenon gas inhaled for 24 hours |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Subcutaneous fat necrosis | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Research Integrity Officer | Imperial College London | +44 020 7594 1872 | jrco@imperial.ac.uk |
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| ID | Term |
|---|---|
| D020925 | Hypoxia-Ischemia, Brain |
| D001927 | Brain Diseases |
| ID | Term |
|---|---|
| D002545 | Brain Ischemia |
| D002561 | Cerebrovascular Disorders |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
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| ID | Term |
|---|---|
| D054020 | Lasers, Gas |
| ID | Term |
|---|---|
| D007834 | Lasers |
| D055096 | Optical Devices |
| D004864 | Equipment and Supplies |
| D055618 | Radiation Equipment and Supplies |
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| Derived |
| Shankaran S. Outcomes of hypoxic-ischemic encephalopathy in neonates treated with hypothermia. Clin Perinatol. 2014 Mar;41(1):149-59. doi: 10.1016/j.clp.2013.10.008. |
| BG002 | Total | Total of all reporting groups |
| Mean |
| Standard Deviation |
| weeks, gestation |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Units | Counts |
|---|---|
| Participants |
|
|
| Primary | Cerebral Fractional Anisotropy Measured by Diffusion Weighted Magnetic Resonance Imaging | 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 | Posted | Mean | Standard Deviation | units on a scale | 10 days |
|
|
|
| Secondary | Amiel Tison Evaluation at 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. | Infants survivors at time of hospital discharge | Posted | Count of Participants | Participants | At discharge from hospital |
|
|
|
| 11 |
| 46 |
| 0 |
| 46 |
| 2 |
| 46 |
| EG001 | Hypothermia and Standard Intensive Care | 72 hours of whole body cooling to 33.5 rectal and standard intensive care | 9 | 46 | 0 | 46 | 0 | 46 |
| Transient desaturation during MRI scan | General disorders | Systematic Assessment |
|
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| D002534 | Hypoxia, Brain |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D000860 | Hypoxia |
| D012818 | Signs and Symptoms, Respiratory |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| Very abnormal |
|