Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12617000271303
Ethics application status
Approved
Date submitted
15/02/2017
Date registered
22/02/2017
Date last updated
14/07/2022
Date data sharing statement initially provided
26/02/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Feasibility and efficacy of using lung measurements to predict complications during surgery for young children with and without asthma.
Scientific title
Feasibility and efficacy of using lung inflammation and mechanics measurements to predict respiratory complications during general anaesthesia for young children with and without asthma.
Secondary ID [1] 291190 0
Nil Known
Universal Trial Number (UTN)
Not applicable
Trial acronym
SAGA - Safety Asthmatics under General Anaesthesia
Linked study record
Not applicable

Health condition
Health condition(s) or problem(s) studied:
Asthmatics having general anaesthesia 302085 0
Condition category
Condition code
Anaesthesiology 301715 301715 0 0
Anaesthetics
Respiratory 301716 301716 0 0
Asthma
Respiratory 301740 301740 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
Following voluntary written informed consent by a parent or legal guardian and child assent, measurements of exhaled nitric oxide and forced oscillation lung function testing will be carried out on the ward prior to the child being taken to theatre.

Techniques:
Exhaled nitric oxide (eNO):
Exhaled NO will be measured using a Niox Vero (Aerocrine, Sweden). Briefly, the child will place the measurement end of the device to his/her lip and perform a normal but continuous exhalation. The device will then measure the level of eNO and display the corresponding value on the screen attached. Either three acceptable measurements within 10% of each other or two measurements within 5% of each other will be made according to international guidelines of the European Respiratory Society (ERS) and the American Thoracic Society (ATS). These measurements are used regularly by our research group.

Forced Oscillation Technique
The Forced Oscillation Technique (FOT) will be used to provide information regarding the resistance of the airways and the reactance (stiffness) of the lung tissues. This quick and easy test during normal tidal breathing does not require any active effort by the child and is completed in less than 5 minutes. FOT is a clinically validated technique routinely used by our group. Briefly, the FOT system superimposes a small amplitude sound wave within a given range of frequencies over the tidal breathing of the child (Tremoflo (registered trademark), THORASYS Thoracic Medical Systems Inc., Canada). The participants will wear a nose clip and perform tidal breathing via a mouthpiece with cheek supported. Three to five measurements within 10% of each other are required according to the international guidelines from the European Respiratory Society and American Thoracic Society.


Both measurements will be completed with participants on the day of surgery, on the ward prior to going to theatre. Appropriately trained and delegated researchers will perform the measurements. Measurements should take less than 30 minutes with each participant.
Intervention code [1] 297192 0
Early Detection / Screening
Comparator / control treatment
The study will have a test group and a control group of participants. The test group will have respiratory risk factors. The control group will be a group of children who do not have asthma or any current respiratory symptoms (wheeze, wheeze during exercise, persistent cough).
The control group will perform the same tests (eNO and FOT)
Control group
Active

Outcomes
Primary outcome [1] 301112 0
The feasibility of using a simple and objective screening approach to identify children at an increased risk of perioperative respiratory adverse events (PRAE) prior to surgery by quantification of airway inflammation and assessment of respiratory mechanics. Feasability will be assessed by the rate of patients who can successfully complete the measurements on the day of surgery.
Timepoint [1] 301112 0
Measurements completed prior to anaesthesia induction on the ward. Perioperative respiratory adverse events (PRAE) will be assessed throughout anaesthesia by anaesthetists (induction, maintenance, emergence, recovery phases) and in recovery ward after surgery by nurses.
Secondary outcome [1] 331757 0
The effect size of the incidence of perioperative respiratory adverse events (PRAE) between children with active respiratory symptoms such as asthma, wheeze and persistent dry nocturnal cough and children with no risk factors (controls). PRAE are assessed by anaesthetist during procedure and by post anaesthesia care unit (PACU) nurse in the recovery unit after the procedure. Events are documented in real time.
Timepoint [1] 331757 0
perioperative respiratory adverse events (PRAE) will be assessed throughout anaesthesia (induction, maintenance, emergence, recovery phases) and in recovery ward after surgery.

Eligibility
Key inclusion criteria
Children, aged 4 to 10 years of age, male and female, undergoing elective surgery under general anaesthesia at our site.
Test group:
1 or more respiratory risk factors:
*Wheeze (more than or equal to 3 times) over past year
*Recurrent respiratory symptoms during exercise in the past year
*Persistent dry cough in last 12 months

Control group:
*No doctor diagnosed active respiratory symptoms as listed in test group
*Can have family history of:
*Hay fever
*Asthma
*Eczema
Minimum age
4 Years
Maximum age
10 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria:
*Cystic Fibrosis, bronchiectasis (doctor diagnosed conditions)
*Cardiac or Thoracic surgery
*Doctor diagnosed cardiac diseases
*Known major Syndromes
*Use of ketamine or midazolam premedication
*Contraindication to the use of sevoflurane
*Less than 32 weeks gestational age
*Recent cold

Study design
Purpose
Screening
Duration
Cross-sectional
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
Statistical analysis
Receiver Operating Characteristic curve (ROC) analysis will be used to assess the predictive capacity of eNO. These data will demonstrate the feasibility of this technique and can then be used for refined sample size calculations for larger studies that will follow.
The FOT data obtained will be assessed against existing reference ranges for the Australian paediatric population while correcting for major confounders such as age and height.
Binary logistic regression will be used to assess the significance of the effect size in occurrence of PRAE between children with active respiratory symptoms and those without any risk factors for PRAE. The data will also provide us with more precise guidance as to the variance expected for each group in terms of occurrence of PRAE.

Sample size calculation
In our forerunner studies we assessed the capacity of eNO to predict occurrence of perioperative respiratory adverse events. A ROC analysis showed an estimated area under the curve (AUC) of 0.62 (95% confidence interval: 0.52-0.71). A similar AUC was seen for risk factors alone (AUC: 0.630, 95% confidence interval: 0.58-0.70). If eNO was combined with the presence of any risk factors for PRAE the AUC increased to 0.73 (95% confidence interval: 0.63-0.83), although this was not statistically different. The rate of PRAE observed in that study was 16.9% and 43.5% in children without risk factors and those with active respiratory symptoms, respectively.
In this proposed pilot study, we are targeting active respiratory symptoms for PRAE which are known to be strongly associated with airway inflammation. We thus expect exhaled nitric oxide to have a higher predictive capacity than in our previous study. We have arbitrarily set an AUC of greater than 0.8 as increasing the prediction of PRAE to a clinically meaningful level above risk factors alone and therefore warranting the development of interventional randomised clinical trials from which changes to clinical practice could be based.
Based on a power calculation for confidence intervals for the area under the ROC curve, a sample size of 50 subjects free of any risk factors in the control group with an expected rate of PRAE of 16.9% and 50 subjects with at least one active respiratory symptom in the test group with an expected rate of PRAE of 43.5%, will produce a two-sided 95% confidence interval of (0.71-0.89) when the sample AUC is at least 0.800.
Based on our experience in a surgical environment, we need to account for a 15% dropout rate due to poor quality data or withdrawal from study. Therefore, a total sample size of 120 children will be required.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
17/04/2017
Actual
25/05/2017
Date of last participant enrolment
Anticipated
30/06/2022
Actual
16/11/2021
Date of last data collection
Anticipated
30/07/2022
Actual
16/12/2021
Sample size
Target
120
Accrual to date
Final
120
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 7496 0
Princess Margaret Hospital - Subiaco
Recruitment hospital [2] 13257 0
Perth Children's Hospital - Nedlands
Recruitment postcode(s) [1] 15321 0
6008 - Subiaco
Recruitment postcode(s) [2] 25817 0
6009 - Nedlands

Funding & Sponsors
Funding source category [1] 295633 0
Charities/Societies/Foundations
Name [1] 295633 0
Australia and New Zealand College of Anaesthetists
Country [1] 295633 0
Australia
Funding source category [2] 295636 0
Hospital
Name [2] 295636 0
Princess Margaret Hospital
Country [2] 295636 0
Australia
Primary sponsor type
Individual
Name
Prof Britta Regli-von Ungern-Sternberg
Address
Department of Anaesthesia and Pain Management
Perth Children's Hospital
15 Hospital Avenue
Nedlands
WA 6009
Country
Australia
Secondary sponsor category [1] 294476 0
Hospital
Name [1] 294476 0
Perth Children's Hospital
Address [1] 294476 0
15 Hospital Avenue
Nedlands
WA 6009
Country [1] 294476 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 296950 0
Children and Adolescent Health Service Human Research Ethics Committee
Ethics committee address [1] 296950 0
Ethics committee country [1] 296950 0
Australia
Date submitted for ethics approval [1] 296950 0
17/01/2017
Approval date [1] 296950 0
28/03/2017
Ethics approval number [1] 296950 0
RGS0000000015

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 72522 0
Prof Britta Regli-von Ungern-Sternberg
Address 72522 0
Department of Anaesthesia and Pain Management, Perth Children's Hospital, Nedlands, WA 6009
Country 72522 0
Australia
Phone 72522 0
+61 8 93408109
Fax 72522 0
Email 72522 0
[email protected]
Contact person for public queries
Name 72523 0
Britta Regli-von Ungern-Sternberg
Address 72523 0
Department of Anaesthesia and Pain Management, Perth Children's Hospital, Nedlands, WA 6009
Country 72523 0
Australia
Phone 72523 0
+61893408109
Fax 72523 0
Email 72523 0
[email protected]
Contact person for scientific queries
Name 72524 0
Britta Regli-von Ungern-Sternberg
Address 72524 0
Department of Anaesthesia and Pain Management, Perth Children's Hospital, Nedlands, WA 6009
Country 72524 0
Australia
Phone 72524 0
+61893408109
Fax 72524 0
Email 72524 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Study is ongoing, no decision taken by investigators yet


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.