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Trial registered on ANZCTR


Registration number
ACTRN12614000739617
Ethics application status
Approved
Date submitted
23/06/2014
Date registered
11/07/2014
Date last updated
8/06/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
REACT: Reducing anaesthetic complications in children undergoing tonsillectomies
Scientific title
Does inhaled salbutamol decrease the incidence of perioperative respiratory adverse events in children undergoing tonsillectomy (+/- adenoids/grommets) procedures?
Secondary ID [1] 284860 0
None
Universal Trial Number (UTN)
Trial acronym
REACT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Respiratory complications under general anaesthetic in children undergoing tonsillectomy (+/- adenoids/grommets) procedures. 292259 0
Condition category
Condition code
Anaesthesiology 292607 292607 0 0
Anaesthetics
Respiratory 292608 292608 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 ( 200micrograms ventolin, GSK) via a metered dose inhaler (pMDI) and a spacer. The placebo/salbutamol will be administered in the 60 minutes prior to anaesthesia induction. The attending anaesthetists, the surgeon , anaesthetic technician, the nursing and recovery staff as well as the research staff will be blinded to the group allocation. Only the pharmacy will be unblinded.
Intervention code [1] 289662 0
Treatment: Drugs
Comparator / control treatment
Inhaled placebo administered via a metered dose inhaler (pMDI) and a spacer in the 60 minutes prior to anaesthesia induction.
Control group
Placebo

Outcomes
Primary outcome [1] 292453 0
The incidence of Perioperative respiratory adverse events (PRAE) in children undergoing tonsillectomy receiving either a premedication of inhaled salbutamol or placebo as assessed via clinical assessments. PRAE include Bronchospasm, Laryngospasm, oxygen desaturation, airway obstruction, coughing and stridor.
Timepoint [1] 292453 0
Perioperative period until the patient is discharged from the Post anaesthesia Care Unit (PACU)
Secondary outcome [1] 308986 0
The secondary outcome is to reduce costs to the hospital by reducing time spent in the PACU due to PRAE.
Timepoint [1] 308986 0
Lenght of time spent in PACU measured and recorded on PACU records and study data sheets.
Secondary outcome [2] 309323 0
The secondary outcome is to reduce costs to the hospital by reducing the number of unplanned admissions to the hospital due to PRAE.
Timepoint [2] 309323 0
This will be measured in the patients notes in the post operative period.
Secondary outcome [3] 309324 0
The secondary outcome is to reduce costs to the hospital by reducing the prolonged hospital stays due to PRAE.
Timepoint [3] 309324 0
Measured in the post operative period and as per detailed in the patients notes.

Eligibility
Key inclusion criteria
We will study 484 children, aged 0-8 years, undergoing general anaesthesia for elective tonsillectomy (+/- adenoidectomy, +/- grommets).
There will be two patient groups for the study:
Group one: Children 0-6 years old receiving an endotracheal tube (ETT)
Group two: Children 3-8 years old receiving a Laryngeal mask airway (LMA)
Minimum age
0 Years
Maximum age
8 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Children receiving a sedating premedication (e.g. midazolam, clonidine) before surgery.
Children with a known difficult airway or thoracic malformation.
Children with a known cardiopulmonary disease:
Uncorrected congenital heart disease
Primary/secondary pulmonary hypertension
Cardiac/thoracic malformations/tumours
Structural lung changes
The above list is a non-exhaustive list. Any other less common cardiopulmonary conditions will be assessed by the anaesthetist in charge and accounted for in the exclusion criteria list.

Study design
Purpose of the study
Treatment
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)
Computer generated block randomisation.
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
The primary aim of this study is to investigate the difference in prevalence of PRAE between the intervention (salbutamol) and control (placebo) groups. This project will investigate the effects of salbutamol on PRAE, separately for the two different airway devices commonly used, an ETT will be used for 0-6 year old children and an LMA will be used for 3-8 year old children. In our recently completed randomised controlled trial involving tonsillectomy, the prevalence of PRAE was 48.2%. We aim to reduce the prevalence to 24.1% +/- 5%. We conservatively selected the upper limit of prevalence of 29.1% (24.1%+5%) for our power and sample size calculation. For the ETT group (for 0-6 year old children), we need 110 children for the intervention and the control groups, respectively, to detect a decreased prevalence of PRAE by 19% (48.2%-29.1%), with a power of 0.8 and at the significance of 0.05. Likewise for our study purpose in the LMA group (for 3-8 year old children), we need the same number of children (n=110) in the intervention and control groups, respectively. Therefore we require 440 children to take part in this project. Furthermore, based on our previous experience, approximately 10% of the data will not be usable due to changes in clinical requirements for the particular patients or due to patient withdrawal and we thus have to add 10% to our sample size calculation to keep the study appropriately powered. We will therefore recruit 484 patients.

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
Recruitment hospital [1] 2664 0
Princess Margaret Hospital - Subiaco
Recruitment postcode(s) [1] 8328 0
6008 - Subiaco

Funding & Sponsors
Funding source category [1] 289472 0
Charities/Societies/Foundations
Name [1] 289472 0
Princess Margaret Hospital Foundation
Address [1] 289472 0
68 Hay street
Subiaco
WA 6008
Country [1] 289472 0
Australia
Primary sponsor type
Hospital
Name
Princess Margaret Hospital
Address
Roberts Road
Subiaco
WA 6008
Country
Australia
Secondary sponsor category [1] 288182 0
None
Name [1] 288182 0
Not applicable.
Address [1] 288182 0
Country [1] 288182 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 291229 0
Princess Margaret Hospital for Children Ethics Committee
Ethics committee address [1] 291229 0
Roberts Road
Subiaco
WA 6008
Ethics committee country [1] 291229 0
Australia
Date submitted for ethics approval [1] 291229 0
Approval date [1] 291229 0
22/05/2014
Ethics approval number [1] 291229 0
EP2014042

Summary
Brief summary
Despite the development of anaesthesia management guidelines, PRAE remain a major cause of morbidity and mortality during paediatric anaesthesia, accounting for more than three quarters of critical incidents and nearly one third of all perioperative cardiac arrests.
It is known that the rate of PRAE is approximately 2-folds higher in children undergoing tonsillectomy procedures compared to adults and that the rate of complications is also inversely proportional to age. Younger children are at a higher risk for PRAE compared with older children with a decrease in PRAE of 11% with each yearly increase in age.
In recent studies and audits in our institution looking at children undergoing tonsillectomies, we found that approximately half the patients suffer from PRAE. Such a high rate of complications inevitably generates a cascade of linked events such as delays in theatre, with the potential for cancellation of other children due to the lack of theatre time and consecutive increases in waitlist time, unplanned hospital admissions, prolonged hospital stay and additional treatment. Even though most PRAE are not associated with long-term sequelae, it also creates more stress for the child and parents. Furthermore, data from closed malpractice claims in the United States of America (USA) show that nearly half of all claims were due to PRAE with higher incidents of death and brain damage as well as higher compensation payments in children as compared with adults.
The development of preventative strategies, incorporated into an optimised anaesthesia management, would help reduce the occurrence of PRAE and address the previously cited issues. Salbutamol is a commonly used drug in the treatment of asthma which is available as an over the counter medication in Australia. A previous observational trial showed that premedication with inhaled salbutamol reduced the incidence of respiratory adverse events and in particular reduced bronchospasm and persistent cough by up to 50% in children with a recent upper respiratory tract infection. This current study aims to test the efficacy of inhaled salbutamol to prevent PRAE in young children undergoing tonsillectomies, who are at a particularly high risk for PRAE in a randomised controlled setting. The secondary objectives are to reduce the delays in theatre and the time spent in PACU due to PRAE, the number of unplanned admissions, prolonged hospital stays and delays in the waiting lists due to sequelae following PRAE.

Hypothesis
We hypothesise that, in children undergoing tonsillectomy (+/- adenoidectomy, +/- grommets) procedures, the incidence of overall PRAE will be significantly reduced by the preoperative treatment with inhaled salbutamol as compared with placebo.
Trial website
Not applicable
Trial related presentations / publications
Not applicable
Public notes

Contacts
Principal investigator
Name 47454 0
Prof Britta Regli-von Ungern-Sternberg
Address 47454 0
Department of Anaesthesia and Pain Management Princess Margaret
Hospital for Children Roberts Road Subiaco WA 6008
Country 47454 0
Australia
Phone 47454 0
+61893408109
Fax 47454 0
Email 47454 0
britta.regli-vonungern@health.wa.gov.au
Contact person for public queries
Name 47455 0
Prof Britta Regli-von Ungern-Sternberg
Address 47455 0
Department of Anaesthesia and Pain Management Princess Margaret
Hospital for Children Roberts Road Subiaco WA 6008
Country 47455 0
Australia
Phone 47455 0
+61893408109
Fax 47455 0
Email 47455 0
britta.regli-vonungern@health.wa.gov.au
Contact person for scientific queries
Name 47456 0
Prof Britta Regli-von Ungern-Sternberg
Address 47456 0
Department of Anaesthesia and Pain Management Princess Margaret
Hospital for Children Roberts Road Subiaco WA 6008
Country 47456 0
Australia
Phone 47456 0
+61893408109
Fax 47456 0
Email 47456 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