Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12618000210279
Ethics application status
Approved
Date submitted
10/01/2018
Date registered
9/02/2018
Date last updated
13/08/2021
Date data sharing statement initially provided
21/03/2019
Type of registration
Retrospectively registered

Titles & IDs
Public title
Nasal High Flow therapy for Children with Acute Hypoxemic Respiratory Failure
Scientific title
Nasal High Flow therapy versus standard oxygen delivery for Children with Acute Hypoxemic Respiratory Failure - a Randomised Controlled Trial to evaluate hospital length of stay and treatment failure.
Secondary ID [1] 293701 0
Nil
Universal Trial Number (UTN)
Trial acronym
PARIS 2 (Paediatric Acute Respiratory Intervention Studies)
Linked study record
Nasal High Flow therapy for Children with Acute Hypoxemic Respiratory Failure - a Randomised Controlled Trial (Pilot Trial)
ACTRN12615001305516

Health condition
Health condition(s) or problem(s) studied:
Acute respiratory failure 306047 0
Condition category
Condition code
Respiratory 305186 305186 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Nasal High Flow Oxygen Delivery at a weight prescribed flow rate for the duration of oxygen requirement. Initially FiO2 is set at 0.21 and SpO2 observed for 10 minutes. If SpO2 remains less than 90/92% (hospital threshold dependent) after 10 minutes then FiO2 is increased and titrated to achieve SpO2 greater than or equal to 90/92%. If patient presents with SpO2 less than 85% then FiO2 is immediately increased to achieve SpO2 equal to or greater than 90/92%. FiO2 is adjusted to achieve and maintain SpO2 of 90/92-98% avoiding long periods of hyperoxia with SpO2 of 100%. For any flow rates greater than 25 L/min the flow rates are increased gradually over two minutes at commencement, and observe how the flow rates are tolerated. These alterations are made by the treating physician or nurse in attendance and recorded on the patients respiratory observation chart.
Intervention code [1] 299956 0
Treatment: Devices
Comparator / control treatment
Standard subnasal 100% O2 is offered at a rate of 0-2 L/min for children up to 2 years of age via subnasal prongs, and for older children, via a face mask or venturi mask with a maximum of 8L/min and O2 flow rate titrated to achieve SpO2 of 90/92-98%. The study design is only prescriptive for the oxygen delivery method. For the remaining respiratory management the individual hospital internal protocols will be followed, including pharmacological management.
Control group
Active

Outcomes
Primary outcome [1] 304341 0
Hospital length of stay assessed by medical records
Timepoint [1] 304341 0
Following discharge from hospital.
Secondary outcome [1] 341637 0
To compare the health care costs between NHF therapy compared with standard oxygen therapy through review of medical records and current industry cost.
Timepoint [1] 341637 0
During study period
Secondary outcome [2] 341638 0
Proportion of intensive care admissions per treatment arm
Timepoint [2] 341638 0
During hospital admission
Secondary outcome [3] 341639 0
Complication of death as assessed by review of hospital medical records
Timepoint [3] 341639 0
During entire hospital admission
Secondary outcome [4] 341640 0
Incidence of adverse events as assessed by reviewing hospital medical records (eg. pneumothorax, cardiac arrest etc)
Timepoint [4] 341640 0
During entire hospital admission
Secondary outcome [5] 341642 0
To perform a subgroup analysis for children with obstructive/reactive airway disease for hospital length of stay
Timepoint [5] 341642 0
Post determination of discharge diagnosis based on DRG
Secondary outcome [6] 341643 0
Tolerance of allocated therapy using visual analogue scale
Timepoint [6] 341643 0
At two time points the tolerance of allocated therapy will be measured. The first timepoint occurs within one hour of therapy commencement.
The second timepoint occurs at some point during 4-48 hrs post commencement of allocated therapy. This wide time period is due to some patients being on the therapy only a few hours and also based on the results of the pilot data where patients are in hospital on average <48hrs. We want to ensure we capture the comfort level prior to removal of therapy. We capture date/time on both measurements. Measurements are taken by both clinician and parent/guardian at the same time for each time period.
Secondary outcome [7] 341644 0
Respiratory support other than oxygen or high flow, provided (such as bubble CPAP, nasal CPAP, non-invasive ventilation or intubation with mechanical ventilation)
Timepoint [7] 341644 0
During entire hospital admission
Secondary outcome [8] 341645 0
At any change in therapy or escalation of care, clinical triggers are measured.
This bundle of clinical triggers include measuring: heart rate, respiratory rate, oxygen requirement, early warning tool trigger/score, work of breathing, level of consciousness, cardiovascular function with impaired peripheral perfusion if any, staffing levels, seniority of clinician making the decision, involvement of ICU review.
Timepoint [8] 341645 0
During entire hospital admission
Secondary outcome [9] 342600 0
Proportion of transfers to hospitals with onsite intensive care units.
Timepoint [9] 342600 0
During entire hospital admission
Secondary outcome [10] 342601 0
Length of additional respiratory support other than oxygen or high flow such as bubble CPAP, nasal CPAP, non-invasive ventilation or intubation with mechanical ventilation.
Timepoint [10] 342601 0
During entire hospital stay

Eligibility
Key inclusion criteria
Children aged 1-4 years of age (up to but excluding 5th birthday) with the clinical diagnosis of an Acute Hypoxemic Respiratory Failure disease process such as acute lower respiratory tract infection or asthma, or pnuemonia as examples, and an oxygen requirement in room air (SpO2 <90/92%)
Included are infants with reactive airway disease >12 months and an oxygen requirement in room air (SpO2 <90/92%). This includes infants >12 months with the diagnosis of bronchiolitis
Informed consent from parents or guardians
Minimum age
1 Years
Maximum age
4 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Oxygen requirement and therapy in the emergency department existed for longer than 4 hours prior to inclusion (excludes oxygen given in ambulance or other hospital)
Previous use of NHF therapy
Upper airway obstruction
Craniofacial malformations
Critically ill infants requiring immediate higher level of respiratory support i.e. NIV or invasive ventilation, low level of consciousness.
Basal skull fracture
Cyanotic Heart Disease
Home Oxygen therapy
Apnoeas (defined as requiring respiratory support such as NIV or mechanical ventilation)
Trauma
Cystic Fibrosis
Oncology patients
Palliative Care patients
Child protection case

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)
Children with respiratory failure in either the emergency department or ward will be screened.
Subjects that meet inclusion and exclusion criteria will be randomised by a central randomisation by a computer.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Subjects that meet inclusion and exclusion criteria will be randomly assigned 1:1 ratio to either Nasal High Flow therapy or standard care. Simple randomisation using a randomisation table created by computer software will be used (i.e. computerised sequence generation).
Randomisation will occur in two groups - obstructive and non-obstructive. Each group will be randomly assigned 1:1 ratio to either Nasal High Flow therapy or standard care.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Descriptive statistics will be used to report on the baseline characteristics of the total study cohort stratified by treatment group. Kaplan-Meier plots with a log-rank test will be used to describe and compare length of hospital stay and duration of oxygen therapy. Analyses of secondary outcomes will be based on chi-square test for proportions and independent samples t-test for continuous measures (or Mann-Whitney U test for non-normally distributed outcomes). Exploratory analyses will be conducted on the subset of patients who require escalation of treatment. These are conditional analyses that are not based on comparing complete randomised groups hence caution is needed when interpreting the results. We also plan to compare ICU length of stay between treatment groups for the subgroup of patients that are admitted to ICU. All analyses will be by intention-to-treat. Statistical significance is set at the 0.05 level.

Sample size calculation is based on a two-sided, randomised trial design with total length of hospital stay as the primary outcome and survival analysis as the primary method of analysis. We consider a difference in length of hospital stay of at least half a day as clinically meaningful, however for the sample size calculation this will be reduced to 0.4 day to increase the sample size to adjust for the effect of clustering. Therefore, if we assume a median length of hospital stay in the control therapy arm of 2 days (based on pilot data), compared with a median length of hospital stay in the NHF arm of 1.6 days, 5% level of significance and 90% power we require 1209 children. To allow for up to 20% non-compliance we require 1512 children in total; 756 in each treatment group. We have demonstrated in our previous NHMRC trial that we are able to follow strict enrolment processes well within the targeted recruitment rates. We estimate a 50-80% enrolment rate of eligible patients.

A recruitment period over three-four winter seasons (southern hemisphere) will occur from end of 2017 to end of 2021.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
15/12/2017
Date of last participant enrolment
Anticipated
31/12/2021
Actual
27/03/2020
Date of last data collection
Anticipated
31/12/2021
Actual
27/03/2020
Sample size
Target
1512
Accrual to date
Final
1512
Recruitment in Australia
Recruitment state(s)
NSW,QLD,WA,VIC
Recruitment hospital [1] 9656 0
The Royal Childrens Hospital - Parkville
Recruitment hospital [2] 9657 0
Gold Coast University Hospital - Southport
Recruitment hospital [3] 9658 0
Redcliffe Hospital - Redcliffe
Recruitment hospital [4] 9659 0
The Prince Charles Hospital - Chermside
Recruitment hospital [5] 9662 0
Ipswich Hospital - Ipswich
Recruitment hospital [6] 9663 0
Redland Hospital - Cleveland
Recruitment hospital [7] 9664 0
Toowoomba Hospital - Toowoomba
Recruitment hospital [8] 9665 0
The Tweed Hospital - Tweed Heads
Recruitment hospital [9] 9666 0
Monash Medical Centre - Clayton campus - Clayton
Recruitment hospital [10] 9667 0
The Townsville Hospital - Douglas
Recruitment hospital [11] 9668 0
The Children's Hospital at Westmead - Westmead
Recruitment hospital [12] 9669 0
Caboolture Hospital - Caboolture
Recruitment hospital [13] 9670 0
Perth Children's Hospital - Nedlands
Recruitment hospital [14] 9671 0
John Hunter Hospital - New Lambton
Recruitment hospital [15] 19110 0
Queensland Children's Hospital - South Brisbane
Recruitment postcode(s) [1] 18419 0
4101 - South Brisbane
Recruitment postcode(s) [2] 18420 0
3052 - Parkville
Recruitment postcode(s) [3] 18421 0
4215 - Southport
Recruitment postcode(s) [4] 18422 0
4020 - Redcliffe
Recruitment postcode(s) [5] 18423 0
4032 - Chermside
Recruitment postcode(s) [6] 18426 0
4305 - Ipswich
Recruitment postcode(s) [7] 18427 0
4163 - Cleveland
Recruitment postcode(s) [8] 18428 0
4350 - Toowoomba
Recruitment postcode(s) [9] 18429 0
2485 - Tweed Heads
Recruitment postcode(s) [10] 18430 0
3168 - Clayton
Recruitment postcode(s) [11] 18431 0
4814 - Douglas
Recruitment postcode(s) [12] 18432 0
2145 - Westmead
Recruitment postcode(s) [13] 18433 0
4510 - Caboolture
Recruitment postcode(s) [14] 18434 0
6009 - Nedlands
Recruitment postcode(s) [15] 18435 0
2305 - New Lambton
Recruitment outside Australia
Country [1] 9469 0
New Zealand
State/province [1] 9469 0
Auckland and South Auckland (2 sites)

Funding & Sponsors
Funding source category [1] 298318 0
Government body
Name [1] 298318 0
National Health and Medical Research Council
Country [1] 298318 0
Australia
Funding source category [2] 298319 0
Other
Name [2] 298319 0
E.W. "AI" Thrasher Award (Thrasher Research Fund)
Country [2] 298319 0
United States of America
Funding source category [3] 298320 0
Hospital
Name [3] 298320 0
Queensland Children's Hospital
Country [3] 298320 0
Australia
Primary sponsor type
Other Collaborative groups
Name
Paediatric Critical Care Research Group
Address
Paediatric Critical Care Research Group
Level 7, Centre for Children’s Health Research
Queensland Children's Hospital Precinct
62 Graham Street, South Brisbane QLD 4101
Country
Australia
Secondary sponsor category [1] 297434 0
None
Name [1] 297434 0
Address [1] 297434 0
Country [1] 297434 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 299313 0
Children’s Health Queensland Human Research Ethics Committee Level 7, Centre for Children’s Health Research Queensland Children's Hospital Precinct 62 Graham Street, South Brisbane QLD 4101
Ethics committee address [1] 299313 0
Ethics committee country [1] 299313 0
Australia
Date submitted for ethics approval [1] 299313 0
Approval date [1] 299313 0
11/12/2017
Ethics approval number [1] 299313 0
HREC/15/QRCH/159

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

Contacts
Principal investigator
Name 80018 0
A/Prof Andreas Schibler
Address 80018 0
Queensland Children's Hospital Level 4A - PICU 501 Stanley St South Brisbane Qld 4101
Country 80018 0
Australia
Phone 80018 0
+617 3068 5733
Fax 80018 0
Email 80018 0
[email protected]
Contact person for public queries
Name 80019 0
Donna Franklin
Address 80019 0
Queensland Children's Hospital Level 4A - PICU 501 Stanley St South Brisbane Qld 4101
Country 80019 0
Australia
Phone 80019 0
+617 3068 5733
Fax 80019 0
Email 80019 0
[email protected]
Contact person for scientific queries
Name 80020 0
Andreas Schibler
Address 80020 0
Queensland Children's Hospital Level 4A - PICU 501 Stanley St South Brisbane Qld 4101
Country 80020 0
Australia
Phone 80020 0
+617 3068 5733
Fax 80020 0
Email 80020 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
No Ethical approval for this data sharing.


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
1618Study protocol https://bmjopen.bmj.com/content/9/12/e030516.abstract  Protocol has now been published on BMJ Open Frank... [More Details] 374240-(Uploaded-28-07-2021-09-13-47)-Study-related document.pdf
12720Statistical analysis plan    Statistical Analysis plan has not been published i... [More Details] 374240-(Uploaded-29-07-2021-16-23-23)-Study-related document.pdf



Results publications and other study-related documents

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

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseMulticentre, randomised trial to investigate early nasal high - Flow therapy in paediatric acute hypoxaemic respiratory failure: A protocol for a randomised controlled trial - A Paediatric Acute respiratory Intervention Study (Paris 2).2019https://dx.doi.org/10.1136/bmjopen-2019-030516
EmbaseEffect of Early High-Flow Nasal Oxygen vs Standard Oxygen Therapy on Length of Hospital Stay in Hospitalized Children with Acute Hypoxemic Respiratory Failure: The PARIS-2 Randomized Clinical Trial.2023https://dx.doi.org/10.1001/jama.2022.21805
N.B. These documents automatically identified may not have been verified by the study sponsor.