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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.
Updated from
failure rate of control or HFNC intervention defined as failure to meet fixed respiratory and heart rate thresholds, trigger of hospital internal warning tool to escalate treatment and increased oxygen requirement  
Reason: The wording of the primary outcome has been re-phrased but not changed to reflect the exact wording of the published protocol in:

Franklin D, Dalziel S, Schlapbach LJ, 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;15:183

Updated on 16/10/2017 5:05:57 PM
Updated from
Reduction in Transfer Rate from Regional Hospital to Tertiary Centre  
Reason: inclusion of tertiary centres, hence the initial outcome -referral to tertiary hospital- is not applicable anymore for patients who present directly to a tertiary ED
Updated on 17/11/2015 10:27:05 AM
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
Updated from
Lenght of Stay in Hospital  
Reason: mispelling
Updated on 16/10/2017 5:05:57 PM
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.
Updated from
infants with bronchiloitis less than 12 months of age<br />oxygen requirement with SpO2<94% in room air  
Reason: Six participating tertiary centres in our study have a lower threshold of < 92% as their standard practice of hospital care. In these sites a threshold of < 92% was accepted in the randomised design, different saturation thresholds in different centres will be balanced through randomisation across all sites. This approach has been introduced to facilitate the study in each of the participating hospitals. These changes are refelcted in the published protocol:

Franklin D, Dalziel S, Schlapbach LJ, 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;15:183.

Updated on 16/10/2017 5:05:57 PM
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
Updated from
carniofacial malformation<br />impending intubation  
Reason: incorrect spelling
Updated on 17/11/2015 10:27:05 AM

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.
Updated from
based on pilot data with a 2.5 reduction in PICU admission and an expected 50% reductionof transfer rate and using a power of 80% a sample size of 300 patients per treatment group is needed. General mixed model, ANOVA  
Reason: inclusion of additional centers and new definition of end points
Updated on 17/11/2015 10:27:05 AM

Recruitment
Recruitment status
Active, not recruiting
Updated from
Recruiting  
Reason: Final patient enrolled 15th August 2016 and trial stopped ahead of schedule with >1400 patients enrolled across 17 centres
Updated on 10/07/2017 3:39:55 PM
Updated from
Not yet recruiting  
Reason: recruitment started 4 November 2013
Updated on 17/11/2015 10:27:05 AM
Date of first participant enrolment
Anticipated
Actual
Updated from
 
Reason: delayed funding
Updated on 17/11/2015 10:27:05 AM
Date of last participant enrolment
Anticipated
Actual
Updated from
 
Reason: delayed funding
Updated on 17/11/2015 10:27:05 AM
Updated from
 
Reason: >1400 patients enrolled by this date so stopped trial.
Updated on 10/07/2017 3:39:55 PM
Date of last data collection
Anticipated
Actual
Updated from
31/12/2017 
Reason: Continue to have Ethics approval until 2023 as this has enabled us to continue to analyse the data further, for future publications
Updated on 4/03/2020 9:42:36 AM
Updated from
31/08/2017 
Reason: Data cleaning post enrollment and data verification on sites
Updated on 16/10/2017 5:05:57 PM
Updated from
 
Reason: 17 centres to capture clean data will take some months to obtain
Updated on 10/07/2017 3:39:55 PM
Sample size
Target
Accrual to date
Final
Updated from
600 
Reason: recalculated new primary outcome
Updated on 17/11/2015 10:27:05 AM
Updated from
1400 
Reason: Final number recruited and included in the analysis for publication
Updated on 4/03/2020 9:42:36 AM
Updated from
 
Reason: stopped trial as >1400 patients enrolled
Updated on 10/07/2017 3:39:55 PM
Recruitment in Australia
Recruitment state(s)
ACT,NSW,QLD,VIC
Updated from
NSW<br />QLD<br />  
Reason: expansion of trial
Updated on 17/11/2015 10:27:05 AM
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
Updated from
New Zealand  
Reason: Starship Children's Health
KidzFirst, Middlemore Hospital
these are the two centres which we would like mentioned if possible as they are a large part of trial

Updated on 23/11/2015 1:47:15 PM
Inserted
 
Reason: expansion of trial
Updated on 17/11/2015 10:27:05 AM
State/province [1] 7334 0
Auckland
Updated from
Auckland  
Reason: We like to add the Auckland sites for visibility:
KidzFirst Middlemore Hospital and Starship Children's Health Auckland

Updated on 16/10/2017 5:05:57 PM
Inserted
 
Reason: expansion of trial
Updated on 17/11/2015 10:27:05 AM

Funding & Sponsors
Funding source category [1] 286998 0
Government body
Name [1] 286998 0
NHMRC
Updated from
National Health Medical Research Ccouncil (NHMRC) (pending)  
Reason: funding received
Updated on 17/11/2015 10:27:05 AM
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
Inserted
 
Reason: start up funding received
Updated on 17/11/2015 10:27:05 AM
Name [2] 292389 0
Queensland Emergency Medical Research Fund
Inserted
 
Reason: start up funding received
Updated on 17/11/2015 10:27:05 AM
Address [2] 292389 0
2/15 Lang Parade, Milton Qld 4064
Inserted
 
Reason: start up funding received
Updated on 17/11/2015 10:27:05 AM
Country [2] 292389 0
Australia
Inserted
 
Reason: start up funding received
Updated on 17/11/2015 10:27:05 AM
Primary sponsor type
Individual
Name
Andreas Schibler
Address
Lady Cilento Children's Hospital
Stanley Street 501
South Brisbane 4101
Queensland, Australia
Updated from
Mater Children's Hospital<br />Paediatric Intensive Care Unit<br />Stanley Street<br />South Brisbane, 4101 QLD  
Reason: move into new facility
Updated on 17/11/2015 10:27:05 AM
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
Updated from
Not yet submitted  
Reason: HREC/13/QRCH/93
Updated on 17/11/2015 10:27:05 AM
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
Updated from
Royal Childern's Hospital
Herston Street
Herston 4006 QLD
 
Reason: They have moved - new address is above
Updated on 23/11/2015 1:47:15 PM
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
Updated from
 
Reason: approved
Updated on 17/11/2015 10:27:05 AM
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
Updated from
Mater Children's Hospital
Paediatric Intensive Care Unit
Stanely Street
South Brisbane 4101 QLD
 
Reason: New mandatory field on ANZCTR registration form and move to new hospital
Updated on 17/11/2015 10:27:05 AM
Country 38938 0
Australia
Phone 38938 0
+61(0)730681111
Updated from
+61(0)731638111  
Reason: New mandatory field on ANZCTR registration form and move to new hospital
Updated on 17/11/2015 10:27:05 AM
Fax 38938 0
Email 38938 0
a.schibler@uq.edu.au
Updated from
icuch5@mater.org.au  
Reason: new facility and institution
Updated on 17/11/2015 10:27:05 AM
Contact person for public queries
Updated from
A/Prof  
Reason: Study Coordinator can continue to update this registry for all future queries. This RCT was her PhD and knows the study very well.
Updated on 4/03/2020 9:42:36 AM
Name 38939 0
Dr Donna Franklin
Updated from
Andreas Schibler  
Reason: Study Coordinator can continue to update this registry for all future queries. This RCT was her PhD and knows the study very well.
Updated on 4/03/2020 9:42:36 AM
Address 38939 0
Queensland Children's Hospital (formerly Lady Cilento Children's Hospital)
Level 7
62 Graham Street
South Brisbane Qld 4101
Updated from
Lady Cilento Children's Hospital, Stanley Street, South Brisbane 4101 QLD Australia  
Reason: Study Coordinator can continue to update this registry for all future queries. The hospital name has since changed to Queensland Children's Hospital
Updated on 4/03/2020 9:42:36 AM
Updated from
Mater Children's Hospital
Paediatric Intensive Care Unit
Stanely Street
South Brisbane 4101 QLD
 
Reason: move to new hospital
Updated on 17/11/2015 10:27:05 AM
Country 38939 0
Australia
Phone 38939 0
+61 7 3069 7000
Updated from
+61(0)730681111  
Reason: This updated number is the research offices and has greater ability of contacting a relevant person.
Updated on 4/03/2020 9:42:36 AM
Updated from
+61(0)731638111  
Reason: move to new hospital
Updated on 17/11/2015 10:27:05 AM
Fax 38939 0
Email 38939 0
d.franklin2@uq.edu.au
Updated from
a.schibler@uq.edu.au  
Reason: Study Coordinator can continue to update this registry for all future queries.
Updated on 4/03/2020 9:42:36 AM
Updated from
icuch5@mater.org.au  
Reason: new facility and institution
Updated on 17/11/2015 10:27:05 AM
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
Updated from
Lady Cilento Children's Hospital, 501 Stanley Street, South Brisbane 4101 QLD Australia  
Reason: The hospital name has since changed to Queensland Children's Hospital

Updated on 4/03/2020 9:42:36 AM
Updated from
Lady Cilento Children's Hospital, Stanley Street, South Brisbane 4101 QLD Australia  
Reason: number of street was missing
Updated on 23/11/2015 1:47:15 PM
Updated from
Mater Children's Hospital
Paediatric Intensive Care Unit
Stanely Street
South Brisbane 4101 QLD
 
Reason: move to new hospital
Updated on 17/11/2015 10:27:05 AM
Country 38940 0
Australia
Phone 38940 0
+61 7 30697000
Updated from
+61(0)730681111  
Reason: This updated number is the research offices and has greater ability of contacting a relevant person.
Updated on 4/03/2020 9:42:36 AM
Updated from
+61(0)731638111  
Reason: move to new hospital
Updated on 17/11/2015 10:27:05 AM
Fax 38940 0
Email 38940 0
a.schibler@uq.edu.au
Updated from
icuch5@mater.org.au  
Reason: new facility and institution
Updated on 17/11/2015 10:27:05 AM

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
Updated from
 
Reason: New mandatory fields
Updated on 4/03/2020 9:42:36 AM
No/undecided IPD sharing reason/comment
All relevant data sharing is already published with the main outcome paper. See below itemised components.
Updated from
 

Updated on 4/03/2020 9:42:36 AM
What supporting documents are/will be available?
Study protocol
Statistical analysis plan
Updated from
 

Updated on 4/03/2020 9:42:36 AM
How or where can supporting documents be obtained?
Type [1] 7232 0
Study protocol
Inserted
 
Reason: Originally had SAP as header when it is in relation to the Study protocol so have updated accordingly.
Updated on 4/03/2020 9:42:36 AM
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.
Inserted
 
Reason: Protocol publication outlined above
Updated on 4/03/2020 9:42:36 AM
Link [1] 7232 0
Inserted
 
Reason: New mandatory fields
Updated on 4/03/2020 9:42:36 AM
Email [1] 7232 0
Inserted
 
Reason: New mandatory fields
Updated on 4/03/2020 9:42:36 AM
Other [1] 7232 0
Inserted
 
Reason: New mandatory fields
Updated on 4/03/2020 9:42:36 AM
Attachment [1] 7232 0
Inserted
 
Reason: New mandatory fields
Updated on 4/03/2020 9:42:36 AM
Type [2] 7234 0
Statistical analysis plan
Inserted
 
Reason: Adding SAP as important for readers to see all results including SAP.
Updated on 4/03/2020 9:42:36 AM
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.
Inserted
 
Reason: Adding SAP as important for readers to see all results including SAP.
Updated on 4/03/2020 9:42:36 AM
Inserted
 
Reason: Protocol link outlined above
Updated on 4/03/2020 9:42:36 AM
Email [2] 7234 0
Inserted
 
Reason: Adding SAP as important for readers to see all results including SAP.
Updated on 4/03/2020 9:42:36 AM
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.
Inserted
 
Reason: Adding SAP as important for readers to see all results including SAP.
Updated on 4/03/2020 9:42:36 AM
Inserted
 
Reason: Adding SAP as important for readers to see all results including SAP.
Updated on 4/03/2020 9:42:36 AM
Summary results
Have study results been published in a peer-reviewed journal?
Yes
Updated from
 
Reason: New mandatory fields
Updated on 4/03/2020 9:42:36 AM
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
Inserted
 
Reason: New mandatory fields
Updated on 4/03/2020 9:42:36 AM
Inserted
 
Reason: New mandatory fields
Updated on 4/03/2020 9:42:36 AM
Other publications
Have study results been made publicly available in another format?
Yes
Updated from
 
Reason: New mandatory fields
Updated on 4/03/2020 9:42:36 AM
Updated from
 
Reason: New mandatory fields
Updated on 4/03/2020 9:42:36 AM
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.
Updated from
 
Reason: New mandatory fields
Updated on 4/03/2020 9:42:36 AM