ANZCTR - Registration

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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

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]

none

Universal Trial Number (UTN)

Trial acronym

DAB

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Bronchiolitis

Condition category

Condition code

Infection

Other infectious diseases

Respiratory

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]

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]

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]

Duration of intensive care stay - only at the conclusion of the intensive care stay will this outcome be evaluated

Secondary outcome [1]

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]

Duration of intensive care stay

Secondary outcome [2]

Intensive care length of stay

Timepoint [2]

at discharge from intensive care

Secondary outcome [3]

Hospital length of stay

Timepoint [3]

at discharge from hospital

Secondary outcome [4]

Rate of intubation – the number of children admitted to the intensive care units that require endotracheal intubation

Timepoint [4]

end of intensive care stay

Secondary outcome [5]

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]

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?

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]

The Royal Childrens Hospital - Parkville

Recruitment hospital [2]

Princess Margaret Hospital - Subiaco

Recruitment postcode(s) [1]

3052 - Parkville

Recruitment postcode(s) [2]

6008 - Subiaco

Recruitment outside Australia

Country [1]

New Zealand

State/province [1]

Auckland

Funding & Sponsors

Funding source category [1]

Hospital

Name [1]

Paediatric Intensive Care Unit (PICU)
Royal Children/s Hospital(RCH) Melbourne

Address [1]

flemington rd parkville Victoria 3052

Country [1]

Australia

Primary sponsor type

Hospital

Name

Royal Children's Hospital

Address

flemington rd parkville Victoria 3052

Country

Australia

Secondary sponsor category [1]

Individual

Name [1]

Frank Shann

Address [1]

flemington rd parkville Victoria 3052

Country [1]

Australia

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Royal children's Hospital HREC

Ethics committee address [1]

flemington rd parkville victoria 3052

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

Approval date [1]

14/12/2012

Ethics approval number [1]

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

Dr Ben Gelbart

Address

PICU
Royal Children's Hospital
Flemington Rd
Parkville
Victoria 3052

Country

Australia

Phone

61 3 93455211

Fax

ben.gelbart@rch.org.au

Contact person for public queries

Name

Ben Gelbart

Address

PICU
Royal Children's Hospital
Flemington Rd
Parkville
Victoria 3052

Country

Australia

Phone

61 3 93455211

Fax

ben.gelbart@rch.org.au

Contact person for scientific queries

Name

Ben Gelbart

Address

PICU
Royal Children's Hospital
Flemington Rd
Parkville
Victoria 3052

Country

Australia

Phone

61 3 93455211

Fax

ben.gelbart@rch.org.au

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
ben.gelbart@rch.org.au

What supporting documents are/will be available?

Doc. No.	Type	Citation	Link	Email	Other Details	Attachment
9553	Study protocol			ben.gelbart@rch.org.au
9554	Statistical analysis plan			ben.gelbart@rch.org.au

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

Source	Title	Year of Publication	DOI
Embase	Pragmatic Randomized Trial of Corticosteroids and Inhaled Epinephrine for Bronchiolitis in Children in Intensive Care.	2022	https://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.

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