Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12613000316707
Ethics application status
Approved
Date submitted
7/03/2013
Date registered
20/03/2013
Date last updated
28/10/2020
Date data sharing statement initially provided
28/10/2020
Date results information initially provided
28/10/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
Randomised controlled trial of a combination of Dexamethasone and Adrenaline for infants with Bronchiolitis
Scientific title
Randomised controlled trial of a combination of Dexamethasone and Adrenaline versus standard care to assess duration of positive pressure ventilation for infants admitted to intensive care with Bronchiolitis
Secondary ID [1] 282086 0
none
Universal Trial Number (UTN)
Trial acronym
DAB
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Bronchiolitis 288588 0
Condition category
Condition code
Infection 288917 288917 0 0
Other infectious diseases
Respiratory 288987 288987 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
While in intensive care, patients in the treatment group will receive 0.6 mg/kg dexamethasone intramuscular or intravenously OR 4mg/kg of oral prednisolone as a loading dose, then 1 mg/kg of methylprednisolone intravenous or prednisolone nasogastric or orally 8 hourly for 9 doses (days1-3 of the study), then daily for three days (days 4-6). The route of administration is determined by the presence of an intravenous cannula or tolerance of oral intake for drugs that can be administered by nasogastric tube. This will be determined by the treating clinician. Starting at the same time as the loading dose of dexamethasone, patients will be given adrenaline providing the resting heart rate is <180 beats per minute: If eligible 5 doses of 0.05ml/kg of 1% adrenaline (or 0.5ml/kg of 1/1000 adrenaline) made up to 6ml with 0.9% saline and nebulised using 12L/min of 02 and repeated every 30 minutes to a total of 5 doses, then given 1-4 hourly depending on the patient response for 72 hours, and then as required for a further 3 days while in intensive care. These drugs were chosen as they are commonly used for other inflammatory diseases of the airway of children and have been used in a recent randomised controlled trial in Canadian emergency department for this condition
Intervention code [1] 286690 0
Treatment: Drugs
Comparator / control treatment
Standard therapy for bronchiolitis usually comprises oxygen therapy, positive pressure respiratory support administered by a gas flow device or mechanical ventilator, nutritional support and sedation. Both arms will receive these therapies. Once recruited and randomised, patients will be given either a combination of corticosteroids plus nebulised adrenaline in addition to standard therapy, or standard therapy alone as determined by their random allocation. Dexamethasone and adrenaline are medications that are commonly used in this age group for the treatment of other respiratory infections.
Control group
Active

Outcomes
Primary outcome [1] 289043 0
The study’s primary outcome is the duration of non-invasive or invasive positive pressure support required from the time of admission to the study until discharge from intensive care. Positive pressure ventilation includes therapies such as high flow nasal prong oxygen of 1 L/kg/min, nasopharyngeal continuous positive airway pressure (CPAP) or invasive positive pressure ventilation (IPPV).
Timepoint [1] 289043 0
Duration of intensive care stay - only at the conclusion of the intensive care stay will this outcome be evaluated
Secondary outcome [1] 301632 0
1 Duration of mechanical ventilation – these data are recorded and updated on an hourly basis in the intensive care observation charts which are part of the medical record
Timepoint [1] 301632 0
Duration of intensive care stay
Secondary outcome [2] 301777 0
Intensive care length of stay
Timepoint [2] 301777 0
at discharge from intensive care
Secondary outcome [3] 301778 0
Hospital length of stay
Timepoint [3] 301778 0
at discharge from hospital
Secondary outcome [4] 301779 0
Rate of intubation – the number of children admitted to the intensive care units that require endotracheal intubation
Timepoint [4] 301779 0
end of intensive care stay
Secondary outcome [5] 301780 0
Pressure-rate product if a nasogastric tube tube is already in situ. The pressure-rate product is a way of measuring the strain on the lung. The pressure can be estimated by measuring the transmitted pressure through an existing routinely placed nasogastric tube and then multiplied by the patients respiratory rate. The Pressure-rate product will be measured within the first 24 hours of respiratory support.
Timepoint [5] 301780 0
duration of intensive care stay

Eligibility
Key inclusion criteria
a clinical diagnosis of bronchiolitis, defined as a first or second episode of wheezing or respiratory distress associated with a respiratory tract infection plus either radiological evidence of chest hyperinflation or clinical evidence of prolonged expiration
greater than 37 weeks and less than 18 months of age
no previous admission to this study
admission to intensive care for respiratory distress (not apnoea alone)
recruitment and initiation of the study therapy within 4 hours of admission to intensive care
Minimum age
37 Weeks
Maximum age
18 Months
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Corrected gestational age of less than 37 weeks at time of admission to the intensive care.
Clinical evidence of croup (laryngotracheobronchitis)
Immunosuppressive treatment, including any dose of corticosteroids in the last 7 days.

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)
When admitted to the intensive care unit with the clinical diagnosis of bronchiolitis patients will be screened for inclusion and exclusion criteria. If eligible for the study, consent will be sought from the family/guardian of the child. The consent process will emphasize the voluntary nature of participation and that participation will not benefit the family or child. In the first instance, recruitment will be undertaken by clinicians or researchers who are not clinically caring for the child. The primary investigators and associate investigators will be available to assist with recruitment. Attempts will be made to separate the recruitment process from the primary clinician however in the event that there is no alternative (in particular after hours) this role may fall to the treating clinician. Subjects will not be eligible if they are not recruited within the first four hours of admission. After consent has been obtained, randomisation will be performed using off site computer generated system administered centrally.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The randomisation process will be facilitated by an online randomisation website created by Dr Brent McSharry with the guidance of Dr. Kate Lee (CEBU). Each site will have site specific passwords to enable access to the website and randomisation process. Randomisation will be in blocks and stratified by (i) unit (4 strata), (ii) level of respiratory support (none, non-invasive positive pressure, endotracheal intubation plus mechanical ventilation) at the time of randomisation, and (iii) the presence of a risk factor (either cyanotic congenital heart disease or chronic lung disease requiring oxygen therapy for more than 14 days in the last 6 months). Thus there will be a total of 4 x 3 x 2x2 = 48 strata.
The first two patients at each centre will be used as the run-in patients and will follow the trial protocol, including randomisation. All case report forms (CRFs) will be completed within two weeks of discharge from intensive care, and the data will be reviewed by the study co-ordinating centre within two weeks of the receipt of data. This audit will document the feasibility of the trial and the adherence to the management strategies proposed, and the principal investigator will contact the site investigators to discuss any protocol deviations/violations. The data from these participants will be used as part of the main study.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis
The primary outcome (duration of support) will also be compared between treatment groups in the following subgroups:
1. Participants with cyanotic congenital heart disease
2. Participants born prematurely (defined as <36 weeks gestation)
3. Participants with RSV positive bronchiolitis
4. Participants with chronic lung disease

Recruitment
Recruitment status
Stopped early
Data analysis
Data collected is being analysed
Reason for early stopping/withdrawal
Other reasons/comments
Other reasons
Outlined above: DSMB recommendation to cease recruitment based on the proportion that received the primary outcome and the original inflation of the sample size calculation based on a prior cohort (prior to the high flow nasal prong era) where only 64% received positive pressure support.
Date of first participant enrolment
Anticipated
11/03/2013
Actual
24/07/2013
Date of last participant enrolment
Anticipated
Actual
22/11/2019
Date of last data collection
Anticipated
Actual
24/11/2019
Sample size
Target
306
Accrual to date
Final
211
Recruitment in Australia
Recruitment state(s)
WA,VIC
Recruitment hospital [1] 726 0
The Royal Childrens Hospital - Parkville
Recruitment hospital [2] 727 0
Princess Margaret Hospital - Subiaco
Recruitment postcode(s) [1] 6525 0
3052 - Parkville
Recruitment postcode(s) [2] 6594 0
6008 - Subiaco
Recruitment outside Australia
Country [1] 4901 0
New Zealand
State/province [1] 4901 0
Auckland

Funding & Sponsors
Funding source category [1] 286863 0
Hospital
Name [1] 286863 0
Paediatric Intensive Care Unit (PICU)
Royal Children/s Hospital(RCH) Melbourne
Country [1] 286863 0
Australia
Primary sponsor type
Hospital
Name
Royal Children's Hospital
Address
flemington rd parkville Victoria 3052
Country
Australia
Secondary sponsor category [1] 285655 0
Individual
Name [1] 285655 0
Frank Shann
Address [1] 285655 0
flemington rd parkville Victoria 3052
Country [1] 285655 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 288923 0
Royal children's Hospital HREC
Ethics committee address [1] 288923 0
flemington rd parkville victoria 3052
Ethics committee country [1] 288923 0
Australia
Date submitted for ethics approval [1] 288923 0
Approval date [1] 288923 0
14/12/2012
Ethics approval number [1] 288923 0
32119A

Summary
Brief summary
Bronchiolitis is a common viral infection of the lungs. It is mostly seen in children less than 1 year old, but it does affect children up to 2 years of age. Each year an average of 100 children with severe bronchiolitis need to be admitted for treatment in the intensive care unit. These children experience significant breathing difficulty and many are ill enough to need a machine to help them to breathe. The standard treatment for these children is to support their breathing, and to give them adequate nutrition and fluids. There are no other medications that have been shown to benefit children with bronchiolitis.

Steroids and adrenaline are two medicines that are commonly used to treat children with severe croup or asthma, and recent research suggests that they may help children with mild bronchiolitis. Steroids are an anti-inflammatory medicine, and adrenaline helps to expand inflamed narrowed airways. It is possible that using a combination of these medicines may reduce the amount of respiratory support required for those children admitted to the intensive care unit with bronchiolitis. Some doctors already use this medicine in intensive care because they believe it works, but other doctors do not use this medicine because they do not think there is enough evidence that it works in intensive care patients.

The purpose of this research project is to see whether dexamethasone (a type of steroid) and adrenaline makes a difference in the treatment of children with bronchiolitis in intensive care. Adrenaline and dexamethasone are medicines that are approved for use in children by the Therapeutic Goods Administration, Australia.

We will compare a group of children who receive the standard treatment for bronchiolitis with a group of children who receive the standard treatment plus steroids and adrenaline. We will compare the amount of respiratory support needed, the duration of mechanical ventilation and the length of stay in intensive care and in hospital in both groups. We aim to study a total of 305 children from The Royal Children’s Hospital, Melbourne. This research will also take place at Princess Margaret Hospital for Children in Perth and the Starship Hospital and Middlemore Hopsital in New Zealand.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 38358 0
Dr Ben Gelbart
Address 38358 0
PICU
Royal Children's Hospital
Flemington Rd
Parkville
Victoria 3052
Country 38358 0
Australia
Phone 38358 0
61 3 93455211
Fax 38358 0
Email 38358 0
[email protected]
Contact person for public queries
Name 38359 0
Dr Ben Gelbart
Address 38359 0
PICU
Royal Children's Hospital
Flemington Rd
Parkville
Victoria 3052
Country 38359 0
Australia
Phone 38359 0
61 3 93455211
Fax 38359 0
Email 38359 0
[email protected]
Contact person for scientific queries
Name 38360 0
Dr Ben Gelbart
Address 38360 0
PICU
Royal Children's Hospital
Flemington Rd
Parkville
Victoria 3052
Country 38360 0
Australia
Phone 38360 0
61 3 93455211
Fax 38360 0
Email 38360 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
demographic data - age, sex, comorbidities
microbiological data
respiratory support data - respiratory support types, duration
PICU and hospital length of stay
When will data be available (start and end dates)?
after publication of the manuscript
anticipated to be after July 2021
The data will be available for 5 years
Available to whom?
Researchers with methodologically sound ethics committee approved research protocols
Available for what types of analyses?
only to achieve the aims of the approved protocol
How or where can data be obtained?
Data can be obtained by emailing the primary investigator. Any proposed requests will be brought to the trial management committee for review
[email protected]


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
9553Study protocol  [email protected]
9554Statistical analysis plan  [email protected]



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbasePragmatic Randomized Trial of Corticosteroids and Inhaled Epinephrine for Bronchiolitis in Children in Intensive Care.2022https://dx.doi.org/10.1016/j.jpeds.2022.01.031
N.B. These documents automatically identified may not have been verified by the study sponsor.