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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]

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

Condition category

Condition code

Anaesthesiology

Anaesthetics

Respiratory

Asthma

Respiratory

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]

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]

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]

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]

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]

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?

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)

Recruitment hospital [1]

Princess Margaret Hospital - Subiaco

Recruitment hospital [2]

Perth Children's Hospital - Nedlands

Recruitment postcode(s) [1]

6008 - Subiaco

Recruitment postcode(s) [2]

6009 - Nedlands

Funding & Sponsors

Funding source category [1]

Charities/Societies/Foundations

Name [1]

Australia and New Zealand College of Anaesthetists

Address [1]

630 St Kilda Road,
Melbourne
VIC 3004

Country [1]

Australia

Funding source category [2]

Hospital

Name [2]

Princess Margaret Hospital

Address [2]

Roberts Road
Subiaco
WA 6008

Country [2]

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]

Hospital

Name [1]

Perth Children's Hospital

Address [1]

15 Hospital Avenue
Nedlands
WA 6009

Country [1]

Australia

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Children and Adolescent Health Service Human Research Ethics Committee

Ethics committee address [1]

r CAHS HREC, 15 Hospital Avenue, Nedlands, WA 6009

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

17/01/2017

Approval date [1]

28/03/2017

Ethics approval number [1]

RGS0000000015

Summary

Brief summary

Each year over 10 000 children attend Princess Margaret Hospital for Children (PMH) to have surgery under general anaesthesia, with many more children attending other hospitals at a state and national level. Respiratory complications are the most frequent problem under general anaesthesia, particularly in young children. Over one quarter of children visiting PMH for surgery have asthma or related breathing difficulties. These complications may have an impact on surgical outcomes, may lead to delays and cancelled surgeries as well as unplanned admissions to specialised wards.
 These respiratory complications can be minimised if children at risk are correctly identified preoperatively. Currently, anaesthetists rely on clinical histories to assess this risk. Symptoms such as asthma, wheezing, hay fever and a family history of allergies and asthma amongst others are all associated with a higher risk of respiratory complications under general anaesthesia.
 Over a series of studies, we have observed that children with active respiratory symptoms such as current asthma, wheeze or persistent dry nocturnal cough experience significantly more respiratory complications compared to children with other known risk factors (such as family history of asthma) or no risk factors. Our data suggests that these children have increased airway inflammation and lower lung function; in a previous study, we observed that 7 out of 10 children with active respiratory symptoms who had airway inflammation experienced respiratory complications during surgery.
 The use of new screening techniques that allow assessment of the risk for respiratory complications by measuring airway inflammation and changes in lung function would help anaesthetists to better assess this risk. This would then allow the anaesthetist to tailor a personalised anaesthesia management to minimise the risk for these complications.
 This pilot study aims to assess the feasibility of an innovative personalised approach, easily applicable to young children to significantly improve the prediction of respiratory complications prior to surgery.  Males and females aged 4 to 10 years of age will be recruited after voluntary informed consent and will complete two tests prior to their surgery. Tests include measuring airway inflammation using the exhaled nitric oxide test and measuring lung mechanics using the forced oscillation technique.
 Strong evidence of successful use of these screening techniques will pave the way to dramatically change surgical and anaesthetic risk management prior to surgery and lead to improved health outcomes for children, their families and the broader health-care system.

Trial website

None

Trial related presentations / publications

None yet

Public notes

Contacts

Principal investigator

Name

Prof Britta Regli-von Ungern-Sternberg

Address

Department of Anaesthesia and Pain Management, Perth Children's Hospital, Nedlands, WA 6009

Country

Australia

Phone

+61 8 93408109

Fax

britta.regli-vonungern@health.wa.gov.au

Contact person for public queries

Name

Britta Regli-von Ungern-Sternberg

Address

Department of Anaesthesia and Pain Management, Perth Children's Hospital, Nedlands, WA 6009

Country

Australia

Phone

+61893408109

Fax

britta.regli-vonungern@health.wa.gov.au

Contact person for scientific queries

Name

Britta Regli-von Ungern-Sternberg

Address

Department of Anaesthesia and Pain Management, Perth Children's Hospital, Nedlands, WA 6009

Country

Australia

Phone

+61893408109

Fax

Britta.Regli-VonUngern@health.wa.gov.au

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

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

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No documents have been uploaded by study researchers.

Documents added automatically

No additional documents have been identified.

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