Clinical trial NCT07024771: Severity of Hypoxic Ischemic Encephalopathy and Neurological Pupil Index in Neonates
Official title: A Study On Association Between Neurological Pupil Index and Clinical Severity of Hypoxic Ischemic Encephalopathy In Neonates Admitted To Neonatal Neurocritical Care Unit
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Hypoxic Ischemic Encephalopathy (HIE)
Keywords: Neurological pupil index
Hypoxic ischemic encephalopathy
automated pupillometry
neonatal neurocritical care
severity of HIE
therapeutic hypothermia
cooling therapy
NPi
seizures
EEG
Lead sponsor: University of Calgary
Sponsor class: OTHER
First posted: 2025-06-17
Enrollment: 25
Sex: ALL
Maximum age (years): 6
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Neonates ≥35 weeks of GA, with Hypoxic ischemic encephalopathy admitted to neonatal neuro-intensive care unit at Alberta children's hospital, Calgary

Brief summary: The goal of this observational study is to learn if the reactivity of a newborn's eye to light (measured as an index, using a new device -pupillometer) reflect the health of their brain recovering from disruption of blood/oxygen supply during birth (Hypoxic Ischemic Encephalopathy-HIE). The main questions it aims to answer are:

* With a decreasing reactivity index, does the chance of an abnormal electrical function of brain (noted by electroencephalography (EEG)) increase?
* With a decreasing reactivity index, do the odds of an indicator of severe impact on brain health (abnormal brain imaging, seizures, feeding difficulty) increase? Participants will undergo eye examination using the pupillometer instead of the regular penlight, as part of their routine neurological examination. This will not change the way in which the newborn is being treated and managed medically.

Detailed description: BACKGROUND:

A newborn baby diagnosed with Hypoxic ischemic encephalopathy (HIE) needs frequent assessment of brain function which includes assessment of pupils in the eyes. However the traditional penlight does not provide a standard measurement and is not very accurate , as it varies based on interpretation of the observer. A new hand-held, non-contact device known as the automated "pupillometer", not only provides a safe, reliable, accurate measurement of the pupil size, but also provides additional information like Neurological Pupil Index (NPi). This value is used to assess the brain function in adults and older children, but the significance of the same has not been studied in a newborn population.

METHODOLOGY:

An Informed consent will be obtained prior to enrolment of the infant in the study. Neurological examination and pupillary assessment will be done at 5 different timepoints: - first at admission(baseline), followed by 24 hours, 48 hours and 72 hours of life, and once prior to discharge. Measurements will be done in both eyes and lesser score of the two will be considered for analysis. Outcome measures including EEG (which is continuous) and MRI (done on day 5 per unit protocol) will be documented and collated for analysis. This is an observational study and the measurement of NPi will not alter the treatment protocol.

The device has been approved by Health Canada for use across all patient population. This device poses no new risks and is safe to use, as it is a non-contact device and is relatively easy to use. Aseptic precautions will be followed when the device is used.

ANALYSIS:

SAMPLE SIZE CONSIDERATIONS:

This is a novel study, with no pre-existing literature. Hence, an initial small scale pilot study will be undertaken with a convenient sample size of all moderate to severe HIE within a year, with anticipation of 70% recruitment. An estimated sample size of 20-25 will help estimate the effect size, variability of NPi, explore relationship between NPi \& indicators of severity of HIE and further refine study design \& sample size calculation

STATISTICAL ANALYSIS:

Primary outcome:

The primary outcome (abnormal EEG pattern) will be a categorical variable (Yes/No type) The relationship between NPi and the primary outcome will be analysed using logistic regression model and expressed as Odds ratio with 95% confidence intervals.

Secondary outcome:

The secondary outcome (a composite measure of factors which indicate risk for severe HIE (including occurrence of seizure during admission, abnormal MRI finding or persistent feeding difficulty) will be assessed using logistic regression A Receiver-Operator Characteristic curve analysis will evaluate the diagnostic accuracy of NPi in predicting clinical severity of HIE indicating sensitivity \& specificity. Any novel threshold values which can predict the cut-off for abnormal EEG pattern, or risk of severe HIE using other indicators will be identified with AUC \>0.7

Eligibility criteria: Inclusion Criteria:

* Neonates ≥35 weeks of GA, with Hypoxic ischemic encephalopathy admitted to neonatal neuro-intensive care unit at Alberta children's hospital, Calgary will be included in the study

Exclusion Criteria:

* Infants with chromosomal abnormalities/ syndromic associations
* Infants with ocular / orbital injuries or structural anomalies of the eye obscuring the pupillometry measurement
* Infants with inadequate pupillometry data / EEG data

Primary outcomes:
measure: Abnormal EEG pattern
timeFrame: From starting therapeutic hypothermia at admission (baseline) till completion of therapeutic hypothermia (72 hours from starting cooling therapy). EEG will be monitored CONTINUOUSLY during this period of 72 hours
Secondary outcomes:
measure: Abnormal MRI findings
timeFrame: MRI brain will be done and scored between day 4 and day 5 from admission
measure: Presence of seizure
timeFrame: baseline (day of admission) till day 5 after admission
measure: persistent Feeding difficulty
timeFrame: will be assessed at the time of discharge from NICU to home or transfer to ward (anytime between week 1 to week 4)
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: University of Calgary
state: Alberta
Study officials:
affiliation: Cummings school of medicine, University of Calgary
name: Khorshid Mohammad, MD, MSc, FRCP, FRCPC
role: PRINCIPAL_INVESTIGATOR
References:
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