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Trial registered on ANZCTR


Registration number
ACTRN12612000626864
Ethics application status
Approved
Date submitted
6/06/2012
Date registered
12/06/2012
Date last updated
6/07/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
Does inhaled salbutamol decrease the incidence of perioperative respiratory adverse events in children at high risk for respiratory complications?
Scientific title
Does inhaled salbutamol decrease the incidence of perioperative respiratory adverse events in children at high risk for respiratory complications?
Secondary ID [1] 280637 0
none
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
The impact of salbutamol vs placebo on the incidence of respiratory complications in children at a particular high risk for respiratory complications 286649 0
Condition category
Condition code
Anaesthesiology 286938 286938 0 0
Anaesthetics
Respiratory 286939 286939 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
All participants will be recruited at the pre-anaesthetic visit and randomised to receive either an inhaled placebo or inhaled salbutamol (200 mg; Ventolin, GSK) via a Metered Dose Inhaler (pMDI) and spacer approx 30 min prior to surgery. The attending anaesthetists, the surgeon, recovery staff, as well as the research staff undertaking lung function assessments will be blinded to the group allocation.
Intervention code [1] 285033 0
Treatment: Drugs
Comparator / control treatment
All participants will be recruited at the pre-anaesthetic visit and randomised to receive either an inhaled placebo (identical to salbutamol puffer but without salbutmol) or inhaled salbutamol (200 mg; Ventolin, GSK) via a Metered Dose Inhaler (pMDI) and spacer approx 30 min prior to surgery. The propellant used in both puffers is hydrofluoroalkane. The attending anaesthetists, the surgeon, recovery staff, as well as the research staff undertaking lung function assessments will be blinded to the group allocation.
Control group
Placebo

Outcomes
Primary outcome [1] 287285 0
The incidence of perioperative respiratory complications until the patient is discharge from the postanaesthetic care unit will be assessed via clinical assessments
Timepoint [1] 287285 0
Perioperative period until patient is discharged from the postanaesthetic care unit.
Secondary outcome [1] 297829 0
Lung function changes before and after the administration of salbutamol or placebo

Lung Function will be measured prior to surgery using the forced oscillation technique, as described below prior to and 15 minutes following administration of salbutamol or placebo. Mean Zrs from 3-5 acceptable measurements will be obtained as per international guidelines and respiratory resistance, reactance, frequency dependence and area under the reactance curve reported. Baseline values will be expressed as standardised deviation (z) scores using locally derived reference values and bronchodilator response reported as the relative (%) change from baseline. Lung volumes will be assessed at the same time.
Forced oscillation:
The mechanical impedance of the respiratory system (Zrs) will be measured with the modification of the Forced Oscillation Technique (FOT). Briefly, a small-amplitude signal between 4-64 Hz will be delivered to the subject through a mouthpiece and/or LMA (as appropriate) via a low-deadspace wave tube. The averaged Zrs data between 4 and 40 Hz will be evaluated to obtain total respiratory resistance (Rrs) and reactance (Xrs) in line with international guidelines. In addition to the average values the within-breath variations of these parameters as functions of tidal volume and flow will also be determined.
Lung volumes:
Functional residual capacity (FRC) and ventilation distribution (lung clearance index and moment ratios) will be measured using an ultrasonic flow meter (Exhalyzer D with ICU insert, Eco Medics, Duernten, Switzerland) using the multiple breath nitrogen wash-out (MBW). Children will breathe via a mouthpiece (or LMA as appropriate) -with a nose clip in place. Once a stable breathing pattern has been established, 100% O2 is introduced and continued until the exhaled nitrogen concentration is stable and decreased to <1.5%. Washout data are analysed off-line for FRC and global indices of ventilation distribution and will include the lung clearance index, alveolar-based mean dilution numbers and the mixing ratio. An increase in markers of ventilation distribution reflects more inhomogeneous ventilation.
Timepoint [1] 297829 0
prior to and 15 min following the administration of salbutamol or placebo

Eligibility
Key inclusion criteria
Children, aged 6-16 years, male or female, undergoing elective surgery with a laryngeal mask airway. All children have to have 2 or more risk factors for respiratory complications:
1) Upper respiratory tract infection < 2 weeks prior to surgery
2) eczema at present or in the past
3) wheezing in the last 12 months
4) previous asthma (if wheezing in the past year is negative)
5) dry night cough
6) respiratory symptoms with exercise
7) family history of asthma (mother, father and/or siblings)
8) family history of eczema (mother, father and/or siblings)
9) family history of hayfever(mother, father and/or siblings)
10) passive smoke exposure (mother, father, caregiver)
Minimum age
6 Years
Maximum age
16 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Known cardiac disease, airway or thoracic malformations, syndrome, neurological disorder, need for premedication, contraindication for LMA use as assessed by an anaesthetist independent of the study team. Any surgery involving the upper airway, chest or abdomen.

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
All patients will be recruited at the pre-anaesthetic visit. Only patients who meet the inclusion criteria for the study will be enrolled and only after informed consent is given voluntarily by the guardian and by the patient if appropriate. The patients will be randomised by computer generated block randomisation. The next available participant number will be assigned to the patient.
The drug randomisation will be performed by pharmacy at Princess Margaret Hospital. The patient will receive the study drug corresponding with his/her Participant Number. The study drug is in boxes with patient numbers detailed on the outside. The participant number will be used to identify the patient for the duration of the study.
All staff involved with the care of the patient and the data recording and entering will be blinded to the group allocation.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
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

Funding & Sponsors
Funding source category [1] 285402 0
Self funded/Unfunded
Name [1] 285402 0
Address [1] 285402 0
Country [1] 285402 0
Australia
Primary sponsor type
Hospital
Name
Princess Margaret Hospital for Children
Address
Roberts Road
Subiaco, WA 6008
Country
Australia
Secondary sponsor category [1] 284254 0
University
Name [1] 284254 0
The University of Western Australia
Address [1] 284254 0
35 Stirling Highway
Crawley WA 6009
Country [1] 284254 0
Australia
Secondary sponsor category [2] 287119 0
Government body
Name [2] 287119 0
NHMRC
Address [2] 287119 0
National Health and Medical Research Council
GPO Box 1421
Canberra ACT 2601
Country [2] 287119 0
Australia
Secondary sponsor category [3] 287120 0
Government body
Name [3] 287120 0
SHRAC
Address [3] 287120 0
State Health Research Advisory Council (SHRAC)
C/o Research Development Unit
Department of Health
PO Box 8172
Perth Business Centre, WA 6849
Country [3] 287120 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 287414 0
Princess Margaret Hospital for Children Ethics Committee
Ethics committee address [1] 287414 0
Robert Road
Subiaco, WA 6008
Ethics committee country [1] 287414 0
Australia
Date submitted for ethics approval [1] 287414 0
30/04/2012
Approval date [1] 287414 0
21/06/2012
Ethics approval number [1] 287414 0
2009/EP

Summary
Brief summary
Despite the development of anaesthesia management guidelines, perioperative respiratory
adverse events (PRAE) remain a major cause of morbidity and mortality during paediatric
anaesthesia, causing more than three quarters of critical incidents and nearly one third of
all perioperative cardiac arrests.
In a previous large cohort study in over 9000 children, we identified several risk factors
(current or recent upper respiratory tract infection, wheezing >3 times in the last 12
months, eczema, nocturnal dry cough, a family history of asthma, eczema, rhinitis or
passive smoking) which can help in every day clinical practice to identify the children at a
particularly high risk for PRAE. Additionally, we demonstrated in an audit of children with a
recent URTI, that inhaled salbutamol reduced the incidence of perioperative
bronchospasm (5% vs. 11%, p=0.027) and persistent coughing (5.5% vs. 11.5%,
p=0.0314) in the perioperative period. The role of pre-treatment with reliever medications
for other PRAE risk factors (such as asthma, present/past eczema) is unknown. We
therefore propose a double blinded randomised controlled trial of the use of inhaled
salbutamol in children with two or more known risk factors for PRAE on the incidence of
PRAE.
We will randomise 470 children (6-16 years) to receive either inhaled salbutamol or an
inhaled placebo prior to the administration of anaesthesia. We will also assess lung
function before and 15 minutes after the administration of salbutamol or placebo.
Furthermore, we will monitor and record all respiratory complications (laryngospasm,
bronchospasm, severe and persistent coughing, airway obstruction, oxygen desaturation
(<95%) and postoperative stridor).
We hypothesise that children receiving salbutamol will experience significantly less PRAE
when compared with children who did not receive salbutamol preoperatively.
This study may help to reduce the health costs associated with respiratory complications
(e.g. unplanned hospital admissions, prolonged hospital stay, additional treatment) and
may help us to avoid unexpected admissions to the intensive care unit. Additionally, our
findings may lead to a reduction in waiting list times and aid us in deciding the best time for
the child’s surgery. Finally, this study may increase the availability of preventative
strategies that may reduce the numbers of children who have their surgery cancelled due
to respiratory issues. Cancellation of surgery has an adverse economic impact for
hospitals, causes enormous emotional and financial burdens on the child and his/her
family who have made many arrangements to attend hospital. Reducing the number of
cancellations will ease the distress experienced by children and their parents when
surgery does not go ahead as planned, which will have add on effects for child/parent
satisfaction regarding their hospital experience.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 34282 0
Prof Britta Regli-von Ungern-Sternberg
Address 34282 0
Department of Anaesthesia and Pain Management
Princess Margaret Hospital for Children
Roberts Road
Subiaco
WA 6008
Country 34282 0
Australia
Phone 34282 0
+61893408109
Fax 34282 0
Email 34282 0
britta.regli-vonungern@health.wa.gov.au
Contact person for public queries
Name 17529 0
Prof Britta Regli-von Ungern-Sternberg
Address 17529 0
Department of Anaesthesia and Pain Management
Princess Margaret Hospital for Children
Roberts Road
Subiaco, WA 6008
Country 17529 0
Australia
Phone 17529 0
+61893408109
Fax 17529 0
Email 17529 0
britta.regli-vonungern@health.wa.gov.au
Contact person for scientific queries
Name 8457 0
Prof Britta Regli-von Ungern-Sternberg
Address 8457 0
Department of Anaesthesia and Pain Management
Princess Margaret Hospital for Children
Roberts Road
Subiaco, WA 6008
Country 8457 0
Australia
Phone 8457 0
+61893408109
Fax 8457 0
Email 8457 0
britta.regli-vonungern@health.wa.gov.au

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary