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Trial registered on ANZCTR


Registration number
ACTRN12613000388718
Ethics application status
Approved
Date submitted
3/04/2013
Date registered
10/04/2013
Date last updated
4/03/2020
Date data sharing statement initially provided
4/03/2020
Date results information initially provided
4/03/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
High Flow Nasal Cannula Treatment for Viral Bronchiolitis in Infants, a Randomised Controlled Trial
Scientific title
High Flow Nasal Cannula Treatment for Viral Bronchiolitis in Infants, a Randomised Controlled Trial
Secondary ID [1] 282234 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Viral bronchiolitis 288749 0
Condition category
Condition code
Respiratory 289108 289108 0 0
Other respiratory disorders / diseases
Infection 289146 289146 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
High Flow Nasal Cannula Oxygen Delivery at a rate of 2L/kg/min for the duration of oxygen requirement
Intervention code [1] 286844 0
Treatment: Devices
Comparator / control treatment
standard oxygen delivery via face mask or subnasal oxygen with a maximal rate of 2L/min
Control group
Active

Outcomes
Primary outcome [1] 289220 0
The primary outcome is the proportion of infants in each group with treatment failure. Treatment failure of either standard subnasal oxygen or HFNC therapy arm is defined as meeting three out of four specified failure criteria receiving escalation of treatment or higher level of care such as high acuity or intensive care. Treatment failure of either standard subnasal oxygen or HFNC therapy arm is defined if three of the four following criteria are met and an escalation of treatment or level of care is required

a.) heart rate remains unchanged or increased compared to admission/enrollment observations,
b.) respiratory rate remains unchanged or increased compared to admission/enrollment observations,
c.) oxygen requirement in HFNC therapy arm exceeds FiO2 greater than 40% to maintain SpO2 greater than or equal to 92% (or greater than or equal to 94%) or oxygen requirement in standard subnasal oxygen therapy arm exceeds >2L/min to maintain SpO2 greater than or equal to 92% (or greater than or equal to 94%)
d.) hospital internal Early Warning Tool calls for medical review and escalation of care.
Timepoint [1] 289220 0
During Hospital Admission
Secondary outcome [1] 302057 0
Reduction in Intubation Rate
Timepoint [1] 302057 0
During Hospital Admission
Secondary outcome [2] 302113 0
Length of Stay in Hospital
Timepoint [2] 302113 0
During Admission

Eligibility
Key inclusion criteria
Inclusion criteria are infants with a clinical diagnosis of bronchiolitis less than 12 months corrected age (greater than or equal to 37 weeks post-conceptional age) with an oxygen requirement in room air of SpO2 < 92% for tertiary centres and <94% for regional and metropolitan centres.
Minimum age
0 Months
Maximum age
12 Months
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
craniofacial malformation
impending intubation

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)
Randomisation on ED admission using central online randomisation allocation concealment
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
equal random sample per hospital site using a permuated block randomisation
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
In 2011 there were 478 eligible patients admitted to 4 of 8 pilot hospitals (Queensland), of which 80 required transfer to a tertiary paediatric centre (16.7 %). Assuming a conservative baseline rate of failure of standard therapy (need for transfer to a specialist paediatric centre or PICU admission) of 10 %, a 50 % relative reduction to 5 % with a power of 90 % and type I error of 0.05, 582 participants per group are required, resulting in a total sample size of 1164 patients. An attrition rate of approximately 10-20 % is estimated, which gives an overall sample size of 1400.

Recruitment
Recruitment status
Active, not recruiting
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)
ACT,NSW,QLD,VIC
Recruitment hospital [1] 4633 0
The Tweed Hospital - Tweed Heads
Recruitment hospital [2] 4634 0
Gold Coast Hospital - Southport
Recruitment hospital [3] 4635 0
Logan Hospital - Meadowbrook
Recruitment hospital [4] 4636 0
Ipswich Hospital - Ipswich
Recruitment hospital [5] 4637 0
Toowoomba Hospital - Toowoomba
Recruitment hospital [6] 4638 0
Redcliffe Hospital - Redcliffe
Recruitment hospital [7] 4639 0
Redland Hospital - Cleveland
Recruitment hospital [8] 4640 0
Nambour General Hospital - Nambour
Recruitment hospital [9] 4641 0
Redland Hospital - Cleveland
Recruitment hospital [10] 4642 0
Caboolture Hospital - Caboolture
Recruitment hospital [11] 4643 0
Lady Cilento Children's Hospital - South Brisbane
Recruitment hospital [12] 4644 0
The Royal Childrens Hospital - Parkville
Recruitment hospital [13] 4645 0
The Canberra Hospital - Garran
Recruitment hospital [14] 4702 0
The Townsville Hospital - Douglas
Recruitment hospital [15] 4703 0
Monash Medical Centre - Clayton campus - Clayton
Recruitment outside Australia
Country [1] 7334 0
New Zealand
State/province [1] 7334 0
Auckland

Funding & Sponsors
Funding source category [1] 286998 0
Government body
Name [1] 286998 0
NHMRC
Address [1] 286998 0
Level 1
16 Marcus Clarke Street
Canberra ACT 2601
Country [1] 286998 0
Australia
Funding source category [2] 292389 0
Charities/Societies/Foundations
Name [2] 292389 0
Queensland Emergency Medical Research Fund
Address [2] 292389 0
2/15 Lang Parade, Milton Qld 4064
Country [2] 292389 0
Australia
Primary sponsor type
Individual
Name
Andreas Schibler
Address
Lady Cilento Children's Hospital
Stanley Street 501
South Brisbane 4101
Queensland, Australia
Country
Australia
Secondary sponsor category [1] 285782 0
None
Name [1] 285782 0
Address [1] 285782 0
Country [1] 285782 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 289043 0
Children's Health Service Human Research Ethics Committee
Ethics committee address [1] 289043 0
Level 7, Centre for Children’s Health Research
Lady Cilento Children's Hospital Precinct
62 Graham Street, South Brisbane QLD 4101
Ethics committee country [1] 289043 0
Australia
Date submitted for ethics approval [1] 289043 0
08/04/2013
Approval date [1] 289043 0
20/06/2013
Ethics approval number [1] 289043 0
ECO00175

Summary
Brief summary
Bronchiolitis is the leading cause of paediatric hospitalisation in Australia accounting for approximately 8000 admissions annually, of which approximately 500-600 are admitted to a paediatric intensive care unit (PICU) requiring respiratory support. There have been numerous attempts and studies over the last three decades investigating the roles of steroids, salbutamol, adrenalin and inhalation of hypertonic saline in infants with bronchiolitis. None have successfully changed the outcome of the disease or the burden on health care systems. High flow nasal cannula (HFNC) therapy has been used over the last 8 years in paediatrics with reports showing a reduction in the need for non-invasive and invasive ventilation. HFNC reduces the work of breathing, improves the gas exchange and can be applied very early in the disease process as there is little interference with the patients comfort. Despite the existing data, the uptake of HFNC therapy in paediatrics is sporadic. This is, in part, due to a lack of “best practice”. Similarly, many centres do not use the HFNC for bronchiolitis as there are opposing report about its benefit and a lack of consensus on how to use it. This study aims to develop a multi-centre trial and to assess which patients with bronchiolitis benefit using HFNC. For this purpose we will perform a randomised controlled trial comparing current best practice versus HFNC therapy. With the introduction of this simple to use respiratory system in regional hospitals we aim to reduce the need to transfer infants with bronchiolitis to tertiary centres.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 38938 0
A/Prof Andreas Schibler
Address 38938 0
Lady Cilento Children's Hospital, Stanley Street, South Brisbane 4101 QLD Australia
Country 38938 0
Australia
Phone 38938 0
+61(0)730681111
Fax 38938 0
Email 38938 0
a.schibler@uq.edu.au
Contact person for public queries
Name 38939 0
Dr Donna Franklin
Address 38939 0
Queensland Children's Hospital (formerly Lady Cilento Children's Hospital)
Level 7
62 Graham Street
South Brisbane Qld 4101
Country 38939 0
Australia
Phone 38939 0
+61 7 3069 7000
Fax 38939 0
Email 38939 0
d.franklin2@uq.edu.au
Contact person for scientific queries
Name 38940 0
A/Prof Andreas Schibler
Address 38940 0
Queensland Children's Hospital (formerly Lady Cilento Children's Hospital)
Level 7
62 Graham Street
South Brisbane Qld 4101
Country 38940 0
Australia
Phone 38940 0
+61 7 30697000
Fax 38940 0
Email 38940 0
a.schibler@uq.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
All relevant data sharing is already published with the main outcome paper. See below itemised components.
What supporting documents are/will be available?
Study protocol
Statistical analysis plan
How or where can supporting documents be obtained?
Type [1] 7232 0
Study protocol
Citation [1] 7232 0
Franklin, D., et al. Early high flow nasal cannula therapy in bronchiolitis, a prospective randomised control trial (protocol): A Paediatric Acute Respiratory Intervention Study (PARIS). BMC Pediatr, 2015; 15(1): p.183.
Link [1] 7232 0
Email [1] 7232 0
Other [1] 7232 0
Attachment [1] 7232 0
Type [2] 7234 0
Statistical analysis plan
Citation [2] 7234 0
Franklin, D. et al., High-flow Therapy for Infants with Bronchiolitis – A Randomized Trial. N Engl J Med., 2018; 378: 1121-1131.
Email [2] 7234 0
Other [2] 7234 0
The Statistical analysis plan can be located with the main results published paper in the NEJM. The Statistical analysis plan is within the appendix for this paper.
Summary results
Have study results been published in a peer-reviewed journal?
Yes
Journal publication details
Publication date and citation/details [1] 7233 0
Franklin, D. et al., High-flow Therapy for Infants with Bronchiolitis – A Randomized Trial. NEJM, 2018; 378: 1121-1131
Other publications
Have study results been made publicly available in another format?
Yes
Results – plain English summary
Our randomized controlled trial in infants with bronchiolitis treated outside of an intensive care setting demonstrated a significantly lower escalation of care and treatment failure rate when high-flow was used early during the hospital admission as compared to standard-oxygen therapy.