Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12623000321640p
Ethics application status
Submitted, not yet approved
Date submitted
11/03/2023
Date registered
25/03/2023
Date last updated
25/03/2023
Date data sharing statement initially provided
25/03/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
Chest hyperinflation and response to steroids and inhaled adrenaline in children with bronchiolitis admitted to intensive care
Scientific title
Chest hyperinflation and response to corticosteroids and inhaled adrenaline in children with bronchiolitis admitted to intensive care
Secondary ID [1] 309183 0
nil known
Universal Trial Number (UTN)
Trial acronym
DAB-CHEST
Linked study record
ACTRN12613000316707
This linked study is the randomised trial from which the participants of this current study are included.
Gelbart B, McSharry B, Delzoppo C, et al.: Pragmatic Randomized Trial of Corticosteroids and Inhaled Epinephrine for Bronchiolitis in Children in Intensive Care. J Pediatr 2022; 244:17-23 e111

Health condition
Health condition(s) or problem(s) studied:
Bronchiolitis 329315 0
Condition category
Condition code
Respiratory 326260 326260 0 0
Other respiratory disorders / diseases
Infection 326321 326321 0 0
Other infectious diseases

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
Children who participated in the DAB study (ACTRN12613000316707) will be the population for the current study. There will be no active participation from children in the current study. Only demographic, clinical and outcome data will used from the previous linked study. In the DAB study patients in the treatment group received either 0.6 mg/kg dexamethasone intramuscularly or intravenously OR 4mg/kg of oral prednisolone as a loading dose, then 1 mg/kg of methylprednisolone intravenously or prednisolone nasogastrically or orally 8 hourly for 9 doses (days 1-3 of the study), then daily for three days (days 4-6). In addition nebulised adrenaline was administered to those in the treatment arm; five half hourly doses followed by one to 4 hourly doses. Standard care (nutrition, respiratory support and sedation) were provided to children in both arms of the study.
Children who participated in the DAB study (ACTRN12613000316707) and had chest xrays performed at the time of the trial will be the subjects of the current study. Chest xrays will be retrieved and scored for evidence of hyperinflation to determine if the trial interventions were associated with an effect on the primary outcome based on the degree of hyperinflation
Intervention code [1] 325626 0
Diagnosis / Prognosis
Comparator / control treatment
Participants randomised to the control group of the original DAB study (ACTRN12613000316707) will be assessed for this study. Participants in this group received standard therapy for bronchiolitis, which usually comprises oxygen therapy, positive pressure respiratory support administered by a gas flow device or mechanical ventilator, nutritional support and sedation.
Control group
Active

Outcomes
Primary outcome [1] 334136 0
Duration of positive pressure support including the combined duration of either high flow nasal prong oxygen, nasal continuous positive airway pressure and mechanical ventilation as assessed by review of the DAB study data
Timepoint [1] 334136 0
from randomisation until intensive care discharge
Secondary outcome [1] 419446 0
Duration of nasal continuous positive airway pressure plus the duration of mechanical ventilation by review of the DAB study data.
Timepoint [1] 419446 0
from randomisation to discharge from intensive care
Secondary outcome [2] 419447 0
RSV infection as assessed from the DAB trial dataset
Timepoint [2] 419447 0
RSV infection during the study period from randomisation to discharge from intensive care
Secondary outcome [3] 419448 0
Any viral infection during the study period as assessed from the DAB trial dataset
Timepoint [3] 419448 0
During the study period from randomisation to discharge from intensive care

Eligibility
Key inclusion criteria
Children who were recruited in the DAB study (ACTRN12613000316707) and received a chest x ray

The inclusion criteria were

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
• less than 18 months of age
• no previous enrolment 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
0 Days
Maximum age
18 Months
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients with the following will be excluded
• Corrected gestational age of less than 37 weeks at time of admission to the intensive care.
• Clinical evidence of croup (laryngotracheobronchitis)
• Received immunosuppressive treatment, including any dose of corticosteroids, in the last 7days.
• On ECMO or HFOV at the time of enrolment
• Previously enrolled in the study

Study design
Purpose
Duration
Selection
Defined population
Timing
Retrospective
Statistical methods / analysis
The demographic and clinical characteristics will be described using frequencies, proportions and median (interquartile range).
For outcome 1, log-linear regression analysis will be performed to investigate the interaction between lung hyperinflation and the effect of treatment with corticosteroid-adrenaline on the duration of PPS. The analysis will be adjusted for the stratification factors at randomisation (the level of respiratory support, and the presence of chronic lung disease or cyanotic congenital heart disease) with an interaction term for corticosteroid-adrenaline treatment and the degree of lung hyperinflation, and the Stata margins and contrast commands used to determine whether any interaction is uniform across degrees of lung hyperinflation or maximal at mild, moderate or severe lung hyperinflation.
For outcome 2, negative binomial regression adjusted for the stratification variables with robust estimates of variance will be used to investigate the effect of lung hyperinflation and corticosteroids-adrenaline on the duration of CPAP and MV.
For outcomes 1 and 2, for each level of lung hyperinflation, the geometric mean (95% confidence interval) adjusted for the stratification variables will be reported, as well as the median (and interquartile range) duration of PPS, and NCPAP plus mechanical ventilation.
For outcomes 3 and 4, the associations will be assessed using the Mann-Whitney U test and illustrated with bar graphs.

Analyses will be performed to investigate domains within the hyperinflation score that contribute to overall impression of hyperinflation, the linear outcome of duration of PPS and those who received CPAP or mechanical ventilation.

We will investigate the inter-observer agreement of a radiological score of hyperinflation. The inter-observer agreement of the chest x-ray hyperinflation score will be presented in a contingency table of the ordinal rating scale in columns and participants in rows with the number of scores by the raters in each cell. Fleiss’ Kappa will be calculated, and the agreement reported as Coefficient between -1 (absolute disagreement) and 1 (absolute agreement).

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/04/2023
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
211
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
WA,VIC
Recruitment hospital [1] 24265 0
Perth Children's Hospital - Nedlands
Recruitment hospital [2] 24266 0
The Royal Childrens Hospital - Parkville
Recruitment postcode(s) [1] 39805 0
3052 - Parkville
Recruitment postcode(s) [2] 39804 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 25318 0
New Zealand
State/province [1] 25318 0
Auckland

Funding & Sponsors
Funding source category [1] 313381 0
Hospital
Name [1] 313381 0
Royal Children's Hospital
Country [1] 313381 0
Australia
Primary sponsor type
Hospital
Name
Royal Children's Hospital
Address
50 Flemington Rd Parkville 3052 Vic
Country
Australia
Secondary sponsor category [1] 315145 0
Other
Name [1] 315145 0
Murdoch Children's Research Institute
Address [1] 315145 0
50 Flemington Rd, Parkville VIC 3052
Country [1] 315145 0
Australia

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 312598 0
Royal Children's Hospital HREC
Ethics committee address [1] 312598 0
50 Flemington Rd, Parkville VIC 3052
Ethics committee country [1] 312598 0
Australia
Date submitted for ethics approval [1] 312598 0
11/03/2023
Approval date [1] 312598 0
Ethics approval number [1] 312598 0

Summary
Brief summary
The DAB study (ACTRN12613000316707) was a pragmatic, randomised study of corticosteroids and nebulised adrenaline in children with bronchiolitis admitted to intensive care. It showed that, compared to standard care alone, the combination of steroids and nebulised adrenaline reduced the duration of positive pressure respiratory support (PPS). The evidence was particularly strong in the sickest children requiring, continuous positive airway pressure (CPAP) and mechanical ventilation (MV), and those who had Respiratory Syncytial Virus (RSV) infection.
Chest hyperinflation is a common clinical sign in children with severe bronchiolitis. It occurs because of lower airway obstruction during expiration and subsequent gas trapping in the lung. Chest hyperinflation can be identified clinically but it is also a chest x-ray finding with varying severity. Chest x-ray findings include, flattened hemidiaphragms, an increased number of rib markings and widened intercostal spaces. Children with bronchiolitis and hyperinflation may be more responsive to the bronchodilator effects of combination corticosteroid and adrenaline therapy compared to those without hyperinflation. Moreover, hyperinflation may be associated with RSV infection, and the presence of hyperinflation in this group may explain the strong effect of steroids and adrenaline. We hypothesise that the degree of hyperinflation predicts the response to steroids and adrenaline on duration of PPS in children with bronchiolitis. We also hypothesise that hyperinflation is associated with the presence of RSV infection.
The primary aim of this study is to investigate whether chest hyperinflation, based on x-ray findings, predicts the response to corticosteroids and inhaled adrenaline on the duration of positive pressure support in children enrolled in the DAB study. The secondary aims are to investigate whether chest hyperinflation predicts the presence of RSV and human metapneumovirus or other viruses, and to assess the concordance between radiologists of their assessment of the degree of hyperinflation.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 125238 0
Dr Ben Gelbart
Address 125238 0
Paediatric Intensive Care unit
Royal Children’s Hospital
Honorary Fellow, Murdoch Children’s Research Institute
Departments of Critical Care and Paediatrics, The University of Melbourne, Australia
50 Flemington Rd
Parkville 3052
Country 125238 0
Australia
Phone 125238 0
+61 3 93455211
Fax 125238 0
Email 125238 0
ben.gelbart@rch.org.au
Contact person for public queries
Name 125239 0
Dr Ben Gelbart
Address 125239 0
Paediatric Intensive Care unit
Royal Children’s Hospital
Honorary Fellow, Murdoch Children’s Research Institute
Departments of Critical Care and Paediatrics, The University of Melbourne, Australia
50 Flemington Rd
Parkville 3052
Country 125239 0
Australia
Phone 125239 0
+61 3 93455211
Fax 125239 0
Email 125239 0
ben.gelbart@rch.org.au
Contact person for scientific queries
Name 125240 0
Dr Ben Gelbart
Address 125240 0
Paediatric Intensive Care unit
Royal Children’s Hospital
Honorary Fellow, Murdoch Children’s Research Institute
Departments of Critical Care and Paediatrics, The University of Melbourne, Australia
50 Flemington Rd
Parkville 3052
Country 125240 0
Australia
Phone 125240 0
+61 3 93455211
Fax 125240 0
Email 125240 0
ben.gelbart@rch.org.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
data from the randomised trial (the DAB trial) were made available already


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
18570Study protocol  ben.gelbart@rch.org.au 385545-(Uploaded-11-03-2023-19-21-35)-Study-related document.docx



Results publications and other study-related documents

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

Documents added automatically
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