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Trial registered on ANZCTR


Registration number
ACTRN12623000863639
Ethics application status
Approved
Date submitted
12/07/2023
Date registered
11/08/2023
Date last updated
11/08/2023
Date data sharing statement initially provided
11/08/2023
Type of registration
Retrospectively registered

Titles & IDs
Public title
Assessing the utility of 3D facial photography and sleep oximetry for Obstructive Sleep Apnoea severity in infants with Pierre Robin Sequence: A Pilot study
Scientific title
Diagnostic accuracy of 3D facial photography and sleep oximetry in assessing the severity of Obstructive Sleep Apnoea in infants with Pierre Robin Sequence: A Pilot study
Secondary ID [1] 310057 0
Perth children's Hospital foundation - grant number 110083
Universal Trial Number (UTN)
Trial acronym
ChIN-uP: (C) Capture facial photo and (IN) in NICU sleep study (uP) for PRS infants
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Pierre Robin sequence
 330595 0
Obstructive Sleep apnea 330596 0
Condition category
Condition code
Respiratory 327428 327428 0 0
Sleep apnoea
Reproductive Health and Childbirth 327600 327600 0 0
Complications of newborn

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
All infants diagnosed with Pierre Robin Sequence (PRS) admitted to Perth Children’s Hospital (PCH) NICU or referred to PCH outpatient clinic will be recruited after obtaining informed parental consent for 3D facial photography, sleep pulse oximetry and the Ages and Stages Questionnaire-Version 3 (ASQ-3). Polysomnography (PSG) will be simultaneously conducted as the standard care pathway for these infants for clinical management in NICU.

The study involves taking two and three (2D and 3D) photographs of your child’s face and conducting simultaneous sleep oximetry along with a standard sleep study/Polysomnography (PSG).

Facial photography is like taking a photograph with your digital camera at home. All photographs will be taken after appropriate parental consent by the researcher or the clinical photographer at PCH. Two different camera systems may be used. The 2D cameras and/or the Vectra Handheld camera are used in the infant age group and 3dMD fixed system camera for older children. These are portable cameras, much like any digital SLR. Three successive facial images will be taken – right side, front on and left side. A computer automatically stitches these images into a 3D image. Older children may be asked to sit on a stool or their parent’s lap facing two sets of cameras housed in shoebox-size containers mounted to a portable stand. The actual image capture time is less than 2 milliseconds (3DMD camera) and approximately one minute for the Vectra camera. However, each scan may take up to 2- 5 minutes considering that several poses may be required. Time also needs to be allocated to check each scan. The whole process, including height and weight measurement and filling in the questionnaire takes no longer than 10 minutes.

Sleep oximetry will be performed with standard devices used by respiratory and sleep departments at PCH. These include new generation devices Massimo or Nellcor™ bedside SpO2 patient monitoring systems which incorporate the latest digital signal processing technology to enable accurate and reliable readings even during low perfusion or other forms of signal interference and filtering of artefacts due to movements. Sleep oximetry will be conducted simultaneously with Polysomnography (PSG) by attaching the cutaneous sensor to the spare limb of the study participant. The sleep oximetry data will be downloaded and analysed using the standard software used by the respiratory and sleep departments. The report will be reviewed and analysed by the researcher under supervision of the sleep specialist. The time of sleep oximetry will be same as Polysomnography (PSG) and no additional time will be required. It will be performed every time the child needs a Polysomnography (PSG) for clinical reasons as prescribed by the treating clinician.

ASQ-3™ (Ages and Stages Questionnaire) is a screening tool that meets the Australian standards for sensitivity and specificity and is endorsed for use by Community Health services in Western Australia. The ASQ-3™ can be used from 1 month until 66 months. It is a parent-completed questionnaire and consists of a series of questions screening for communication, gross motor, fine motor, problem solving, and personal adaptive skills. It provides a cut-off score in 5 domains of development. a) Red zone (i.e., ASQ score worse than 2SD below the mean) indicates the need for further evaluation and b) a monitoring zone (i.e., ASQ score worse than 1SD below the mean) identifies children who should be monitored and rescreened. The ASQ questionnaires will be sent to parents by post or email after informed consent and will be scored by the researcher on return. These can be completed by the parents/caregivers independently or with the assistance of professionals or administered by a trained professional. The data will be collected as per current standard practice of developmental follow-up at 4, 8, 12 and 24 months.
Intervention code [1] 326465 0
Diagnosis / Prognosis
Comparator / control treatment
Polysomnography (PSG)
It is a procedure that utilizes electroencephalogram, electro-oculogram, electromyogram, electrocardiogram, and pulse oximetry, as well as airflow and respiratory effort, to evaluate underlying causes of sleep disordered breathing. All PSG data will be scored by skilled sleep scientists and reported as per American Academy of Sleep Medicine standards (AASM) under the supervision of paediatric sleep specialists. It will be performed every time the child needs a Polysomnography (PSG) for clinical reasons as prescribed by the treating clinician.
Control group
Active

Outcomes
Primary outcome [1] 335293 0
Severity of retrognathia as assessed on anthropometric measurements on 3D facial photography.
Timepoint [1] 335293 0
Every time a Polysomnography (PSG) is conducted for clinical reasons.
Expected time points: at 2-4 weeks, 6-8 weeks, 4-6 months, 8-12 months and 18-24 months of postnatal age.
Primary outcome [2] 335431 0
Severity of sleep apnea on sleep oximetry as measured with desaturation indices.
Timepoint [2] 335431 0
Every time a Polysomnography (PSG) is conducted for clinical reasons.
Expected time points: at 2-4 weeks, 6-8 weeks, 4-6 months, 8-12 months and 18-24 months of postnatal age.
Secondary outcome [1] 423789 0
Neurodevelopment stage determined by the Ages and Stages Questionnaire-Version 3 (ASQ-3)
Timepoint [1] 423789 0
at 4 months, 8months, 12 months, 24 months
Secondary outcome [2] 424503 0
Type of airway intervention required to treat upper airway obstruction (as recorded in medical records)
Timepoint [2] 424503 0
In first two years of life

Eligibility
Key inclusion criteria
All infants born with a clinical diagnosis of PRS and admitted to the NICU of PCH or referred to the PCH outpatient department in the first 2 years of life will be eligible for inclusion.
Minimum age
0 Days
Maximum age
2 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Anyone wishing to participate will not be excluded from the study, but data from participants who have had radical facial trauma or who have undergone major face-altering surgery will not be included in the analysis.

Study design
Purpose of the study
Diagnosis
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
No applicable
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Not applicable
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



The people analysing the results/data
Intervention assignment
Other
Other design features
Since it is a diagnostic accuracy study, randomisation is not applicable. Blinding will be ensured as described below:
The 3D photography measurements will be analysed by a genetic scientist using Cliniface software and the deidentified measurement will be provided to the investigator. The scientist will be blinded to the results of oximetry, PSG results or other clinical details.

Sleep oximetry data will be downloaded using the standard software by a sleep scientist and only deidentified results will be provided to the investigator. The scientist will be blinded to the results of 3D facial photography, PSG results or other patient clinical details.

PSG will be reported by the respiratory physicians and reports will be available to treating clinicians to enable a management plan, as per current unit guidelines. Clinicians who will report PSG will be blinded to the results of pulse oximetry and 3D photography. The results of the 3D photography and oximetry will not be disclosed to the treating team.

Both oximetry and PSG will be reported as per pre-defined criteria which mitigates the risk of inter and intra-observer variation. 3D facial measurements will be reported by a pre-defined facial anthropometric computer-based software (Cliniface) thereby mitigating human bias.

Flow and timing are also important in diagnostic accuracy studies. Hence, we will ensure that sleep oximetry and PSG are conducted simultaneously. The 3D photography will be conducted within ± 2 weeks of the PSG/oximetry.
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Standard exploratory data analyses will be run. For example, frequencies and percentages will be used to describe categorical variables. Mean and standard deviation will be used to describe normally distributed continuous variables. The median and interquartile ranges will be used for non-normally distributed continuous variables.
We are mainly interested in the counts of severe versus non-severe cases. From this, accuracies (sensitivity and specificity) are the main statistics of interest, calculated from the false positives and false negatives. As all tests were performed on each patient, a method that accounts for the correlated binary outcome such as McNemar’s test will be used to account for the paired data. Restricted maximum likelihood approaches could be used to compare these values between the tests. The first analysis compares sleep pulse oximetry with PSG; the second compares 3D facial photography with PSG.
If the two diagnostic assessments are considered comparable to PSG, we will combine results from the two tests (sleep pulse oximetry and 3D facial photography)—either by pooling the results or adding them together depending on the character of the data. This is done to determine whether the two tests combined are comparable to PSG in assessing the severity of UAO/OSA, providing clinicians with an alternative metric to the PSG.
To address the second objective, exploratory analyses will first be run on the clinical outcome (type of intervention required) and neurodevelopmental outcomes (ASQ results). Subsequently, we will use t-tests, ANOVA, or regression (ordinal or simple depending on the outcomes) to explore the relationship between these outcomes and the three diagnostic tests. Likelihood ratios, a receiver operating characteristic (ROC) curve and the area under the ROC curve (AUC) will be calculated for all three diagnostic tests from our study results.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
6/06/2023
Date of last participant enrolment
Anticipated
31/12/2028
Actual
Date of last data collection
Anticipated
31/12/2033
Actual
Sample size
Target
30
Accrual to date
2
Final
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 25077 0
Perth Children's Hospital - Nedlands
Recruitment postcode(s) [1] 40742 0
6009 - Nedlands

Funding & Sponsors
Funding source category [1] 314224 0
Charities/Societies/Foundations
Name [1] 314224 0
Perth Children's Hospital Foundation
Country [1] 314224 0
Australia
Primary sponsor type
Government body
Name
Perth Children's Hosptial
Address
15 Hospital Avenue, Nedlands, WA Australia 6009
Country
Australia
Secondary sponsor category [1] 316157 0
None
Name [1] 316157 0
Address [1] 316157 0
Country [1] 316157 0
Other collaborator category [1] 282745 0
Other Collaborative groups
Name [1] 282745 0
Cliniface Team
Address [1] 282745 0
https://cliniface.org/
C/O Professor Gareth Baynam,
Director of Rare care centre
Perth Children's Hospital
15 Hospital Avenue, Nedlands, WA Australia 6009
Country [1] 282745 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 313347 0
Child and Adolescent Health Service Human Research Ethics Committee
Ethics committee address [1] 313347 0
15 hospital Avenue, Nedlands, WA, 6009
Ethics committee country [1] 313347 0
Australia
Date submitted for ethics approval [1] 313347 0
05/08/2022
Approval date [1] 313347 0
20/04/2023
Ethics approval number [1] 313347 0
RGS0000005533

Summary
Brief summary
Pierre Robin Sequence (PRS) is a rare (1:8500 live births) congenital condition characterized by micrognathia (small jaw)/retrognathia (receding chin), glossoptosis (posterior and upward displacement of the tongue) and upper airway obstruction. Many infants with PRS have a cleft of the soft palate. The main clinical issue for infants with PRS is upper airway obstruction (UAO) leading to obstructive sleep apnoea (OSA, intermittent brief cessations of breathing while asleep), feeding difficulties and failure to thrive (i.e. very slow weight gain). Polysomnography (PSG), also known as the sleep study is the currently approved tool to objectively assess the severity of OSA but is often difficult to obtain in a timely manner. This could lead to suboptimal care, prolonged hospital stays, parental anxiety, and staff dissatisfaction. Two other bedside tools, sleep pulse oximetry and 3D facial photography, are easier and quicker to perform and have the potential to diagnose OSA in these infants. However, there is currently limited evidence on their diagnostic accuracy in comparison to the gold-standard PSG in infants with PRS. Hence, we aim to conduct a prospective diagnostic accuracy study evaluating whether sleep pulse oximetry and 3D facial photography are non-inferior to PSG in detecting upper airway obstruction in infants with PRS. Additionally, we will explore the association between the severity of upper airway obstruction assessed using PSG, sleep pulse oximetry, and 3D facial photography with the neurodevelopmental outcomes of infants with PRS until two years of age.
Given rarity of the disease, we aim to recruit for 4 years to reach a sample size of 30 with follow-up of each participant up to 2 years of corrected age. Data from study participants will be collected from birth to 24 months of life. The project is recruiting participants with rare conditions and syndromes.
Trial website
Trial related presentations / publications
Public notes
Partnering with consumers: We have reached out to PRS Australia consumer based-group Pierre Robin Australia and obtained preliminary parental input. We aim to continue to partner with the PRS Australia group over the course of this research project.

Contacts
Principal investigator
Name 127826 0
Dr Dimple Goel
Address 127826 0
Neonatal intensive care unit, ward 3B
Perth children's Hospital
15 Hospital Avenue, Nedlands WA 6009
Country 127826 0
Australia
Phone 127826 0
+61 864564174
Fax 127826 0
Email 127826 0
dimple.goel@health.wa.gov.au
Contact person for public queries
Name 127827 0
Dr Dimple Goel
Address 127827 0
Neonatal intensive care unit, ward 3B
Perth Children's Hospital
15 Hospital Avenue, Nedlands WA 6009
Country 127827 0
Australia
Phone 127827 0
+61 864564174
Fax 127827 0
Email 127827 0
dimple.goel@health.wa.gov.au
Contact person for scientific queries
Name 127828 0
Dr Dimple Goel
Address 127828 0
Neonatal intensive care unit, ward 3B
Perth Children's Hospital
15 Hospital Avenue, Nedlands WA 6009
Country 127828 0
Australia
Phone 127828 0
+61 864564174
Fax 127828 0
Email 127828 0
dimple.goel@health.wa.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Due to rarity of disease, it is difficult to maintain patient confidentiality in small number of patients recruited even with de-identified data. Ethical approval has been obtained to publish/share de-identified analysis of results.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.