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Trial registered on ANZCTR


Registration number
ACTRN12617001503314
Ethics application status
Approved
Date submitted
27/09/2017
Date registered
25/10/2017
Date last updated
26/11/2018
Date data sharing statement initially provided
26/11/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Making tonsillectomy surgery safer for children by examining obstructive sleep apnoea
Scientific title
Making Tonsillectomies Safer by examining methods of screening and diagnosis of obstructive sleep apnoea and comparing to airway collapsibility measurements for children undergoing tonsillectomy surgery under general anaesthesia.
Secondary ID [1] 292900 0
None
Universal Trial Number (UTN)
Trial acronym
OSATS2
Linked study record
OSATS study part 1 registration: ACTRN: ACTRN12615001037594

Health condition
Health condition(s) or problem(s) studied:
Respiratory complications under general anaesthetic in children undergoing tonsillectomy (+/-adenoids/grommets) procedures. 304748 0
Sleep Disordered Breathing 304750 0
Condition category
Condition code
Anaesthesiology 304076 304076 0 0
Anaesthetics
Surgery 304077 304077 0 0
Other surgery
Respiratory 304078 304078 0 0
Sleep apnoea

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
1:
Polysomnography (overnight sleep study) will be performed by an experienced sleep scientist or technician with each participant at 2 time points, first within 3 months prior to surgery and second at 6 to 18 weeks after surgery.

2:
A 3D facial picture will be taken with each participant at 2 time points, first within 3 months prior to surgery and second at 6 to 8 weeks after surgery. (at the same time as sleep studies.)

3:
ActiCal (ActiCals’s, Philips Respironics) activity monitoring devices to be worn at 2 time points. On night of both sleep studies plus 7 nights after each sleep study. They will be applied by the research team member and parents advised on care for device at home.

4:
WristOx (Nonin) wrist oxygen saturation device to be worn on night after procedure when in hospital and will be applied by a trained study team member.

I5:
Measurements of airway collapsibility pressure will be carried out at three different perioperative phases;
(1) Just after induction of anaesthesia and prior to insertion of the airway device
(2) At emergence just after the removal of the airway device
(3) In the recovery phase prior to being awake.
Each measurement will be between 15 and 30 seconds and repeated twice to give an accurate result. This involves the use of a nasal mask and requires the patient to be breathing spontaneously while anaesthesia is maintained. A pressure transducer will continuously measures pressure changes within the nasal mask. Airflow and phase of respiratory cycle will be monitored either by a pneumotachograph attached to the nasal mask, or by visually monitoring the patient’s chest wall movement.
After ensuring that the nasal mask is leak free by optimising the seal, at end-expiration it will be occluded and the pressure-time profile monitored for evidence of ‘flattening’ - indicating upper airway collapse. (Breathing will be blocked for between 15 to 30 seconds.) The pressure at which this occurs (termed Pclose) will be recorded. Once the flattening of the curve is observed, the nasal mask is removed and breathing returns to normal. Air flow will be monitored for all patients to ensure adherence to the protocol. All results of airway collapsability will be recorded in a study data collection log.

6:
Completion of sleep study questionnaires (Pediatric Sleep Questionnaire/PSQ: Sleep-Disordered Breathing Subscale and the Sleep Disturbances Scale for Children) at 3 timepoints; Both of the sleep studies and on day of procedure.

7:
A blood sample will be taken on the day of procedure when the child is anaesthetised to verify the red cell distribution width

8:
Validation of Nonin wristox as a diagnostic tool. Monitoring with wristox to pre - and post-surgery sleep studies to allow comparison with the polysomnography data.
Intervention code [1] 299180 0
Diagnosis / Prognosis
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 303512 0
This study will define the capacity of the Pclose (airway collapsibility measurements) to identify the presence and severity of OSA in this population as determined by preoperative polysomnography.
Timepoint [1] 303512 0
Day of procedure when airway collapsibility measurements will be completed and compared to the 2 sleep studies being completed in the 3 months prior to the day of procedure and 6 to 18 weeks after the procedure.
Secondary outcome [1] 339141 0
To assess the relationship between the Pclose (airway collapsibility measurements) and the pre-operative questionnaire results.
Questionnaires used are: Pediatric Sleep Questionnaire/PSQ: Sleep-Disordered Breathing Subscale, and Sleep Disturbances Scale for Children
Timepoint [1] 339141 0
Day of procedure when airway collapsibility measurements) will be completed and compared to the 2 sleep studies being completed in the 3 months prior to the day of procedure and 6 to 8 weeks after the procedure.
Secondary outcome [2] 339142 0
To assess the relationship between the Pclose (airway collapsibility measurements) and the pre-operative respiratory risk factors as assessed by the research team members.
Timepoint [2] 339142 0
Day of procedure when airway collapsibility measurements) will be completed and compared to the data collected pre-operatively at surgical clinic visit plus on day of procedure.
The respiratory risk factors include asking the following questions:
Cold or flu in last 2 weeks
3 or more wheezing events in the past year
Wheezing at exercise in the past year
Previous history of asthma
Nocturnal cough in the past year
Presence of hay fever or eczema
Family history (2 or more parents/siblings/grandparents) with asthma, eczema or hayfever
Exposure to passive smoke.
Secondary outcome [3] 339143 0
To assess the relationship between the Pclose (airway collapsibility measurements) and the perioperative respiratory adverse events
Timepoint [3] 339143 0
Day of procedure when airway collapsibility measurements) will be completed and compared to the data collected during and after anaesthesia for 24 hours after the tonsillectomy procedure.
All perioperative respiratory adverse events (i.e. laryngospasm, bronchospasm, oxygen desaturation [<95%], severe persistent coughing, airway obstruction), will be recorded by an independent observer who is blinded to the results of the measurements (i.e. treating anaesthetist or PACU nurse).
Secondary outcome [4] 339144 0
To assess the relationship between the Pclose (airway collapsibility measurements) and the red cell distribution width
Timepoint [4] 339144 0
Day of procedure when airway collapsibility measurements) will be completed and compared to the blood sample taken on the day of procedure.
Secondary outcome [5] 339147 0
To assess the relationship between the Pclose (airway collapsibility measurements) and the craniofacial measurements from the 3D photographic images
Timepoint [5] 339147 0
Day of procedure when airway collapsibility measurements) will be completed and compared to the 3D pictures taken at the time of the 2 sleep studies being completed in the 3 months prior to the day of procedure and 6 to 8 weeks after the procedure.
Secondary outcome [6] 339148 0
To assess the relationship between the Pclose (airway collapsibility measurements-sensitivity and specificity) and the activity monitor derived measures of sleep.
Timepoint [6] 339148 0
Day of procedure when airway collapsibility measurements) will be completed and compared to the 7 days of activity monitoring completed at the time of the 2 sleep studies being completed in the 3 months prior to the day of procedure and 6 to 8 weeks after the procedure.

Eligibility
Key inclusion criteria
Male or female
Aged 1 to 8 years of age
Undergoing elective surgery under general anaesthetic for tonsillectomy (+/- adenoids, myringotomy, insertion of grommets and/or cautery of inferior turbinates)
Minimum age
1 Years
Maximum age
8 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Need for premedication with midazolam.
Contraindication for the use of sevoflurane
Inability to give informed consent
Children with known cardiopulmonary disease
Significant medical disease or condition that is likely to interfere with the protocol or might be confounded by the protocol.
• Born less than 32 weeks of gestational age

Study design
Purpose
Screening
Duration
Longitudinal
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
This study is an exploratory study comparing the numerical value of Pclose measurements with OSA severity as assessed by PSG. As this particular comparison has never been previously explored the sample size proposed was based on the experience and opinion of our investigators. Moreover, within our sample size, we need to account for unusable data due to clinical/technical reasons and/or voluntary withdrawal. Thus, we believe n=60 will provide us with sufficient information on the comparison of these two variables for an appropriate and more refined sample size calculation for future research on this topic.

Perioperative respiratory complications occur in 30 to 50% of children undergoing tonsillectomy (+/- adenoidectomy) with a number of patients experiencing multiple events. Poisson or negative binomial regression methods will be used to analyse the relationship between the critical pressure at which the airway tends to collapse (Pclose) and the rate of occurrence of PRAE.
Linear regression will be used to analyse the association of pre-operative Pclose measurements with the severity of OSA. We will also examine the STBUR (Snoring, Trouble Breathing, Un-refreshed) and SDSC (Sleep Disturbance Scale for Children) as predictors of OSA severity, and compare the r-squared (proportion of variation explained by the model) and effect sizes between these models to gain an understanding of how Pclose compares to these clinical tools in terms of OSA severity predictive power.
We will also assess the intra-person variability of Pclose measurements at each time point. This will allow us to understand the degree of reliability that Pclose measurements can provide in terms of predicting the severity of OSA. A comparison of the standard deviation to the mean value of the measurements will be carried out for this purpose using the coefficient of variation (relative standard deviation).
Additionally, the sensitivity and specificity of this proposed technique will be extracted from receiver operator characteristic (ROC) curves plotted (Pclose vs occurrence of PRAE/severity of OSA obtained from PSG). The Sensitivity and specificity will be calculated for the capacity of Pclose to predict the presence (i.e. sensitivity – ability of Pclose to correctly identify those with OSA) or absence (i.e. specificity = ability of Pclose to correctly identify those without OSA) of sleep apnoea.

Given the exploratory nature of the study we wish to undertake an interim analysis at n=20 to enable appropriate modification in sample size, study design, and even an early declaration of success. We believe that such an approach is prudent as it will help us analyse and predict the outcomes of this pilot study by incorporating what is learned during the course of the study.
Additionally we have added the Nonin Wristox validation technique to the statistical methods

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 9081 0
Princess Margaret Hospital - Subiaco
Recruitment hospital [2] 9082 0
Perth Children's Hospital - Nedlands
Recruitment postcode(s) [1] 17574 0
6008 - Subiaco
Recruitment postcode(s) [2] 17575 0
6009 - Nedlands

Funding & Sponsors
Funding source category [1] 297531 0
Charities/Societies/Foundations
Name [1] 297531 0
Princess Margaret Hospital Foundation
Address [1] 297531 0
68 Hay St,
Subiaco
WA 6008
Country [1] 297531 0
Australia
Funding source category [2] 297570 0
Other Collaborative groups
Name [2] 297570 0
Australia and New Zealand College of Anaesthetists
Address [2] 297570 0
ANZCA House,
630 St Kilda Road,
Melbourne,
Victoria 3004,
Country [2] 297570 0
Australia
Primary sponsor type
Hospital
Name
Princess Margaret Hospital
Address
Roberts Road
Subiaco
WA 6008
Country
Australia
Secondary sponsor category [1] 296537 0
Individual
Name [1] 296537 0
Prof Britta von Ungern-Sternberg
Address [1] 296537 0
Princess Margaret Hospital
Roberts Road
Subiaco
WA 6008
Country [1] 296537 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 298627 0
Children and Adolescent Health Service Human Research Ethics Committee
Ethics committee address [1] 298627 0
Princess Margaret Hospital
Roberts Road
Subiaco
WA 6008
Ethics committee country [1] 298627 0
Australia
Date submitted for ethics approval [1] 298627 0
14/02/2017
Approval date [1] 298627 0
18/08/2017
Ethics approval number [1] 298627 0
RGS000000014

Summary
Brief summary
Obstructive sleep apnoea (OSA) is a condition involving repeated episodes of partial or complete blockage of the airway during sleep. Children diagnosed with OSA usually undergo surgical removal of the tonsils and adenoids.
However, there is a high rate of complications with approximately 50% of the children suffering from minor or major breathing problems during and/or after surgery requiring specialised care. Additionally, the younger the children are, the higher the risk of breathing problems. The impact on the healthcare system is significant; the number of unplanned admissions necessitating specialised treatment with prolonged hospital stays increases causing delays on theatre lists. This leads to potential cancellations of other children due to the lack of theatre time and consequently increases the waitlist time. The ‘gold standard’ test for diagnosis and classification of OSA is the complex and expensive technique called polysomnography (PSG) (overnight sleep study). The associated high cost and lengthy waiting list means that it is rarely used in clinical practice in this population. Currently, surgeons and anaesthetists assess the children’s risk of respiratory complications through clinical history and questionnaires. However, relying on parental observations alone can make assessment of the presence and severity of OSA challenging. As a result, this screening technique is not sufficient. Children at an increased risk of respiratory problems can be missed through this process & their airway management strategies may not be conservative enough to minimise the risk of respiratory complications during and after their procedure. Since OSA involves a highly collapsible upper airway during sleep and also anaesthesia, we have adopted a method to measure the likelihood of collapse of the upper airway (throat) under anaesthesia to predict OSA severity. This safe, simple and quick technique, that can be implemented in routine practice will provide anaesthetists with a new screening method and allow evidence-based risk stratification of this high risk population and will allow anaesthetists to tailor their management for the individual patient to avoid breathing problems. Alternatively, children with no/mild obstructive sleep apnoea requiring less close observation following surgery will be able to be discharged earlier reducing the overall emotional impact on families by allowing patients to recover in the comfort and familiarity of their own home. This may also reduce overall unnecessary admissions to ICU alleviating some of the economic impact of this problem on the hospitals. This study will also look at other emerging techniques that may estimate OSA severity to examine if they correlate with PSG data and are predictive for respiratory problems. Ultimately, we aim to develop a clinical guideline from some or all of these parameters that will allow improved stratification of preoperative OSA patients without the reliance on PSG.
Trial website
Not applicable
Trial related presentations / publications
None yet
Public notes

Contacts
Principal investigator
Name 77698 0
Prof Britta von Ungern-Sternberg
Address 77698 0
Department of Anaesthesia and Pain Management
Perth Children's Hospital
15 Hospital Avenue
Nedlands
WA 6009
Country 77698 0
Australia
Phone 77698 0
+61 864564805
Fax 77698 0
+61893408755
Email 77698 0
Britta.Regli-VonUngern@health.wa.gov.au
Contact person for public queries
Name 77699 0
Prof Britta von Ungern-Sternberg
Address 77699 0
Department of Anaesthesia and Pain Management
Perth Children's Hospital
15 Hospital Avenue
Nedlands
WA 6009
Country 77699 0
Australia
Phone 77699 0
+61 864564805
Fax 77699 0
+61893408755
Email 77699 0
Britta.Regli-VonUngern@health.wa.gov.au
Contact person for scientific queries
Name 77700 0
Prof Britta von Ungern-Sternberg
Address 77700 0
Department of Anaesthesia and Pain Management
Perth Children's Hospital
15 Hospital Avenue
Nedlands
WA 6009
Country 77700 0
Australia
Phone 77700 0
+61 864564805
Fax 77700 0
+61893408755
Email 77700 0
Britta.Regli-VonUngern@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
Privacy reasons
What supporting documents are/will be available?
Study protocol
Attachments/websites
Type [1] 359 0
Study protocol
URL/details/comments [1] 359 0
will be available
Attachment [1] 359 0
Summary results
Not applicable