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Trial registered on ANZCTR


Registration number
ACTRN12612000685819
Ethics application status
Approved
Date submitted
26/06/2012
Date registered
26/06/2012
Date last updated
8/07/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
Randomised control trial of high-flow nasal prong warm, humidified oxygen (HFNP WHO) compared to standard oxygen therapy in the management of moderate bronchiolitis in infants aged less than or equal to 24 months in the Emergency Department (ED) and Children's Medical Ward of a tertiary referral hospital.
Scientific title
A single site, open, two arm, randomised control trial (RCT), with nested longitudinal observational study, of infants aged less than or equal to 24 months with moderate bronchiolitis to test the effect of high-flow nasal prong warm, humidified oxygen (HFNP WHO) (1L/kg/min total flow with 1:1 air:O2 ratio to a maximum of 20L/min or FiO2 60%) compared to standard nasal prong cold humidified oxygen (2.0L/min maximum flow) on median time to weaning off supplemental oxygen during the acute admission.
Secondary ID [1] 280381 0
N/A
Universal Trial Number (UTN)
U1111-1130-1651
Trial acronym
HFNP WHO RCT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute moderate bronchiolitis 286360 0
Condition category
Condition code
Respiratory 286598 286598 0 0
Other respiratory disorders / diseases
Infection 286600 286600 0 0
Studies of infection and infectious agents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
High-flow, nasal prong, warmed, humidified oxygen delivered via the Fisher & Paykel MR850 with Optiflow Junior(TM) nasal prongs (max. 1.0 L/kg/min; 1:1 air:O2 flow ratio) to a maximum flow rate of 20L/min. Supplemental oxygen will be administered for as long as is clinically necessary to support oxygen saturations greater than or equal to 95% during the admission. Participants on both the intervention and control arms will have the option of participating in the nested longitudinal observational study of Infant Lung Function (09/07/15/5.04 HREC/09/HNE/242) which involves follow-up infant lung function tests and assessments at 1 month and 12 months post-discharge.
Intervention code [1] 284744 0
Treatment: Devices
Intervention code [2] 285166 0
Treatment: Other
Comparator / control treatment
The enrolled infants will move through the ED and Children's Medical Ward allocated to either the experimental treatment or control standard treatment. No humidification with cold low-flow oxygen (max. 2.0 L/min) is standard care in the ED during the acute admission process.
Cold low-flow nasal prong oxygen (max. 2.0 L/min) with an AquaPak humidifier (Hudson RCI, USA) is standard care instituted at the time of admission to the Children's Medical Ward.
Control group
Active

Outcomes
Primary outcome [1] 287019 0
Median time to weaning off supplemental oxygen (hours) following defined weaning criteria based on NSW Health Standard Paediatric Observation Charts and full explained in a standard operating procedure. Weaning of oxygen is successful if the infant remains stable in room air for 6 hours or until discharge, whichever is less.
Timepoint [1] 287019 0
Hours from randomisation to successful weaning to room air (or pre-morbid home-oxygen rate) with treatment failure care included in cases where failure has occurred.
Secondary outcome [1] 297208 0
Proportion and rate of treatment failure. Treatment failure is a clinical judgement based on documented observations, clinical examination, and the clinical decision that a change in treatment is required to prevent further deterioration.
Timepoint [1] 297208 0
Measured at two time points: from randomisation to leaving ED; and from randomisation to successful weaning to room air.
Secondary outcome [2] 297209 0
Mean change from baseline in heart rate, respsiratory rate, and respiratory distress score as recorded hourly on NSW Health Standard Paediatric Observation Charts. .
Timepoint [2] 297209 0
Calculated for ED from observations at baseline and 4 hours (or pre-transfer to ward whichever is less);
and in ward from observations at baseline and 24 hours from standard hourly observations on NSW Health Standard Paediatric Observation Charts.
Secondary outcome [3] 297210 0
Mean length of stay (LOS) as determined by medical records discharge data.
Timepoint [3] 297210 0
Days from admission to discharge.
Secondary outcome [4] 297211 0
Proportion of harms (Adverse events). Adverse events (AEs) will be recorded on the Incident Information Management System (IIMS) and will be rated 1-2 for serious AEs and 3-4 for AEs. The control arm participants may experience decreased feeding due to the irritation of cold gas in the nose; drier thicker sectretions requiring mechanincal suction; and mucousal bleeding. The experimental arm participants may experience decreased feeding from higher flows of gas in the nose; and there is a risk of condensed vapour in the humidifier circuit running back into the nares if the circuit is raised above the level of the infant's nose. A follow-up phone survey will be attended at 30 days post-discharge to surveil for AEs identified by the parent/guardian post-discharge.
Timepoint [4] 297211 0
From recruitment to 30 days post-discharge from acute admission.
Secondary outcome [5] 297212 0
Mean change in severity score using Modified Woods Clinical Asthma Score (M-WCAS). Results will be correlated to the severity rating of NSW Health Standard Paediatric Observation Charts.
Timepoint [5] 297212 0
Measured at baseline and at 4 hours or time of transfer from ED, whichever is less;
and at baseline and daily in the ward.
Secondary outcome [6] 297213 0
Mean scores of parent assessment of quality of feeding, sleep/rest, and safety obtained from a structured eight question phone survey administered 30 days post-discharge.
Proportion of post-discharge medical presentations for related events e.g. re-presentations with bronchiolitis, pneumonia, or potential parent reported adverse events such as pressure areas on the face, ears, head; nose bleeds.
Timepoint [6] 297213 0
30 days post-discharge.
Secondary outcome [7] 297214 0
Biomarker - association between causative organism and severity with organism if identified by Multiplex 10 Polymerase Chain Reaction (PCR).
Timepoint [7] 297214 0
Nasopharyngeal aspirate collected within 24 hours of admission.
Secondary outcome [8] 297215 0
Biomarker - Immune response to virus. Blood examined for anti-viral response.
Timepoint [8] 297215 0
Blood collected at the time of cannulation if the infant requires a cannula as standard clinical care.
Secondary outcome [9] 297216 0
Diagnostic - Accuracy of lung ultrasound to detect lung abnormalities as compared to clinical findings across groups, and compared to available chest xray (CXR) results if attended in individual cases as part of standard clinical care.
Timepoint [9] 297216 0
One at baseline (day 1), and then one or more on day two from recruitment, in the event of treatment failure, and before discharge.

Eligibility
Key inclusion criteria
Consented infants aged less than or equal to 24 months with a clinical diagnosis of moderate bronchiolitis presenting to the ED or Medical Unit . Infants on home oxygen may be included in this study, with weaning aimed to home oxygen rate rather than room air in these cases.
Minimum age
1 Days
Maximum age
24 Months
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Infants with mild bronchiolitis not requiring oxygen (but may be enrolled if the infant’s condition deteriorates and O2 is required after admission).
Those with severe/life-threatening bronchiolitis (as defined by NSW Health, PD 2012_004 Infants and Children - Acute Management of Bronchiolitis)
Infants admitted to ward following ICU management of bronchiolitis.
Infants transferred from other facilities if they have received supplemental oxygen for bronchiolitis prior to arrival.
Infants nursed in other wards due to lack of beds in the medical ward.
Infants on prior asthma prevention or treatment medication.
Infants with pneumothorax and/or nasal trauma

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)
Stratification by defined gestational history (Extreme prem; Prem; Term) is used to control for this covariate.
Consecutive, enrolled participants will be assigned to treatment according to the child's gestational history (stratification - 3 levels) and the allocation will be concealed in the next sequential privacy envelope available for the required stratification level. This procedure is available in the ED and Medical Ward.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computer generated permuted block sequences have been generated and assigned to 3 strata levels.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
RCT includes a nested longitudinal observational study of Infant Lung Function (ILF). HFNP WHO RCT participants will be offered follow-up ILF in a separately consented, HREC approved study(09/07/15/5.04 HREC/09/HNE/242) .
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
16/07/2012
Actual
16/07/2012
Date of last participant enrolment
Anticipated
30/04/2015
Actual
1/05/2015
Date of last data collection
Anticipated
2/10/2015
Actual
10/09/2015
Sample size
Target
202
Accrual to date
Final
202
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 4097 0
John Hunter Children's Hospital - New Lambton

Funding & Sponsors
Funding source category [1] 285518 0
Charities/Societies/Foundations
Name [1] 285518 0
Hunter Children's Research Foundation
Country [1] 285518 0
Australia
Primary sponsor type
Hospital
Name
John Hunter Children's Hospital
Address
Locked Bag 1
Hunter Region Mail Centre
2310. NSW
Country
Australia
Secondary sponsor category [1] 284357 0
Charities/Societies/Foundations
Name [1] 284357 0
Hunter Children's Research Foundation
Address [1] 284357 0
Hunter Medical Research Institute
1/1 Kookaburra Circuit, New Lambton Heights NSW 2305
Country [1] 284357 0
Australia
Other collaborator category [1] 276882 0
Individual
Name [1] 276882 0
Professor Colin Royse
Address [1] 276882 0
The University of Melbourne
Victoria 3010
Australia
Country [1] 276882 0
Australia
Other collaborator category [2] 278548 0
Individual
Name [2] 278548 0
Dr Adam O'Brien
Address [2] 278548 0
The Royal Children's Hospital Melbourne
Flemington Road
Parkville 3052
VICTORIA
Country [2] 278548 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 287531 0
Hunter New England Human Research Ethics Committee
Ethics committee address [1] 287531 0
Ethics committee country [1] 287531 0
Australia
Date submitted for ethics approval [1] 287531 0
Approval date [1] 287531 0
18/06/2012
Ethics approval number [1] 287531 0
HNEHREC - 12/05/16/3.01; NSW HREC HREC/12/HNE/135
Ethics committee name [2] 293236 0
Univeresity of Newcastle
Ethics committee address [2] 293236 0
Ethics committee country [2] 293236 0
Australia
Date submitted for ethics approval [2] 293236 0
Approval date [2] 293236 0
06/08/2012
Ethics approval number [2] 293236 0
H-2012-0259.

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 34102 0
Dr Elizabeth Kepreotes
Address 34102 0
Johgn Hunter Children's Hospital
Locked Bag 1
Hunter Region Mail Centre
2310 NSW
Country 34102 0
Australia
Phone 34102 0
+61 02 49855173
Fax 34102 0
+61 02 49213599
Email 34102 0
[email protected]
Contact person for public queries
Name 17349 0
Elizabeth Kepreotes
Address 17349 0
Locked Bag 1
Hunter Region Mail Centre
NSW
2310
Country 17349 0
Australia
Phone 17349 0
+61 02 49855173
Fax 17349 0
+61 02 49213599
Email 17349 0
[email protected]
Contact person for scientific queries
Name 8277 0
Elizabeth Kepreotes
Address 8277 0
Locked Bag 1
Hunter Region Mail Centre
NSW
2310
Country 8277 0
Australia
Phone 8277 0
+61 02 49855173
Fax 8277 0
+61 02 49213599
Email 8277 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseHigh-flow warm humidified oxygen versus standard low-flow nasal cannula oxygen for moderate bronchiolitis (HFWHO RCT): an open, phase 4, randomised controlled trial.2017https://dx.doi.org/10.1016/S0140-6736%2817%2930061-2
N.B. These documents automatically identified may not have been verified by the study sponsor.