Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12615001305516
Ethics application status
Approved
Date submitted
22/09/2015
Date registered
30/11/2015
Date last updated
20/09/2019
Date data sharing statement initially provided
20/09/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Nasal High Flow therapy for Infants and Children with Acute Hypoxemic Respiratory Failure - Pilot Trial
Scientific title
Feasibility of Nasal High therapy and standard practice for Infants and Children with Acute Respiratory Failure
Secondary ID [1] 287521 0
Nil
Universal Trial Number (UTN)
Trial acronym
PARIS 2 - pilot trial
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute Respiratory Failure 296284 0
Condition category
Condition code
Respiratory 296561 296561 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 92% (hospital threshold dependent) after 10 minutes then FiO2 is increased and titrated to achieve SpO2 greater than or equal to 92%. If patient presents with SpO2 less than 85% then FiO2 is immediately increased to achieve SpO2 equal to or greater than 92%. FiO2 is adjusted to achieve and maintain SpO2 of 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] 292912 0
Treatment: Devices
Intervention code [2] 293050 0
Treatment: Other
Comparator / control treatment
Standard subnasal 100% O2 is offered at a rate of 0-2 L/min for infants up to 2 years of age or 0-4 L/min for children 2years up to 16 years of age, or via a face mask with a maximum of 8L/min and O2 flow rate titrated to achieve SpO2 of 94-98%. 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] 296176 0
The primary outcome is defined by the feasibility to assess the proportion of treatment failure of either control standard oxygen therapy or NHF therapy arm and is assessed if three of the four following criteria are met and an escalation of treatment or level of care is required 1. Heart rate remains >160/min for >2hrs since admission/enrolment observations - assessed through ECG. 2. Respiratory rate remains >45/min for >2hrs since admission/enrolment observations assessed through ECG. 3. To maintain SpO2 92-98%, oxygen requirement in NHF therapy arm exceeds FiO2 equal to or greater than 40% or oxygen requirement in control arm exceeds the following measured with oximetry. Standard subnasal oxygen > 2L/min or >8L/min in children using a hudson mask. 4. Early warning tool triggers a medical review.
Timepoint [1] 296176 0
Treatment failure is monitored for the first 7 days after randomisation and assessed at time when allocated treatment is changed and patient care is escalated to higher level of care.
Secondary outcome [1] 317712 0
To determine the proportion of study participants who were admitted to intensive care at any point during their stay in hospital by review of medical records.
Timepoint [1] 317712 0
At end of study, once all participants have finished treatment.
Secondary outcome [2] 317713 0
To determine the proportion of patients requiring escalation of therapy such as non-invasive or invasive ventilation through review of hospital medical records
Timepoint [2] 317713 0
During hospital admission
Secondary outcome [3] 317714 0
Measurement of complications such as death as a single secondary outcome via review of hospital medical records
Timepoint [3] 317714 0
During entire hospital admission
Secondary outcome [4] 317715 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 [4] 317715 0
During study period
Secondary outcome [5] 345805 0
Measurement of the singular complication pneumothorax by review of hospital medical records
Timepoint [5] 345805 0
During entire hospital admission

Eligibility
Key inclusion criteria
Children aged 0-16 years of age 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 <92%)
Included are infants with reactive airway disease >12 months and an oxygen requirement in room air (SpO2 <92%). This includes infants >12 months with the diagnosis of bronchiolitis.
Informed consent from parents or guardians
Minimum age
No limit
Maximum age
16 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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)
Upper airway obstruction
Trauma
Cystic Fibrosis
Oncology patients
Palliative Care patients
Previous use of NHF therapy
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)
infants and 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
Efficacy
Statistical methods / analysis
Descriptive statistics will be utilised to report on the baseline characteristics of the total study cohort, as well as by site. The primary outcome measure investigating clinical treatment failure will be analysed using test of two proportions, and will be reported as the difference, 95% confidence interval and p-value. The secondary outcome measure investigating length of stay will likely be non-normally distributed, and as such will be analysed using Mann-Whitney U test; if it is normally distributed independent samples t-test will be used. Analysis of secondary outcomes includes both comparisons of measurements and proportions, using confidence intervals of differences as the major method of presentation where possible, otherwise techniques as described previously. All analyses will be by intention-to-treat. Statistical significance will be set at the 0.05 level.

Both parametric and non-parametric bootstrapping techniques will be employed to compare mean difference in the costs between groups, and to estimate a confidence interval around the mean. It is anticipated that NHF therapy will be cost saving to the health system.

There is currently no data on intubation rates and admission rates to intensive care for infants and children requiring NHF therapy for acute respiratory failure. In the State of Queensland Australia with a population of 4.7 million there were between July 2010 and July 2015 1850 infants and children with respiratory failure other than bronchiolitis treated with non-invasive ventilation (336 patients per year) with an average age of 4.02 +/- 4.6 years. This figure approximately represents 10-15 % of these patients admitted to an emergency department and then requiring transfer to PICU for respiratory support.
Approximately 25% of admissions to paediatric intensive care are due to respiratory conditions and approximately 50% of infants and children admitted to a general intensive care unit (ANZPIC Annual Report 2013).

For the Lady Cilento Children’s Hospital, Brisbane, Queensland with an anticipated overall PICU admission rate of 2200 patients/annum, this translates to 550 admissions. Approximately half of these admissions are attributed to bronchiolitis <12 months of age. Hence approximately 250-270 admissions per annum have the above inclusion criteria when presenting to the emergency department of the Lady Cilento Children’s Hospital, which is consistent with the above-mentioned patient numbers. For a 50% reduction (using a power of 80%) from 15% to 7.5% an anticipated sample size of 280 patients will be needed per arm. We will cover the summer and winter season 2015-2016 with recruitment of patients and anticipate enrolling 200-300 patients into the pilot study and test in this convenient sample the feasibility and the suspected reduction in admissions to PICU in view to expand the trail to a fully powered RCT including multiple regional and tertiary centres

Recruitment
Recruitment status
Active, not recruiting
Date of first participant enrolment
Anticipated
1/12/2015
Actual
20/06/2016
Date of last participant enrolment
Anticipated
1/07/2017
Actual
15/12/2017
Date of last data collection
Anticipated
31/12/2020
Actual
Sample size
Target
300
Accrual to date
Final
576
Recruitment in Australia
Recruitment state(s)
QLD,VIC
Recruitment hospital [1] 10746 0
The Royal Childrens Hospital - Parkville
Recruitment hospital [2] 14837 0
Queensland Children's Hospital - South Brisbane
Recruitment postcode(s) [1] 22472 0
3052 - Parkville

Funding & Sponsors
Funding source category [1] 294874 0
Other
Name [1] 294874 0
E.W. "AI" Thrasher Award
Country [1] 294874 0
United States of America
Funding source category [2] 299263 0
Charities/Societies/Foundations
Name [2] 299263 0
Children's Health Foundation
Country [2] 299263 0
Australia
Funding source category [3] 299264 0
Other Collaborative groups
Name [3] 299264 0
Paediatric Critical Care Research Group
Country [3] 299264 0
Australia
Primary sponsor type
Hospital
Name
Lady Cilento Children's Hospital
Address
501 Stanly St
South Brisbane
Queensland 4101
Country
Australia
Secondary sponsor category [1] 290770 0
Other Collaborative groups
Name [1] 290770 0
Paediatric Critical Care Research Group
Address [1] 290770 0
Paediatric Critical Care Research Group
Level 7, Centre for Children’s Health Research
Lady Cilento Children's Hospital Precinct
62 Graham Street, South Brisbane QLD 4101
Country [1] 290770 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 293576 0
Children's Health Service Human Research Ethics Committee
Ethics committee address [1] 293576 0
Ethics committee country [1] 293576 0
Australia
Date submitted for ethics approval [1] 293576 0
Approval date [1] 293576 0
30/09/2015
Ethics approval number [1] 293576 0
HREC/15/QRCH/159

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

Contacts
Principal investigator
Name 60530 0
A/Prof Andreas Schibler
Address 60530 0
Lady Cilento Children's Hospital
501 Stanley St
South Brisbane Qld 4101
Country 60530 0
Australia
Phone 60530 0
+617 3068 5733
Fax 60530 0
Email 60530 0
[email protected]
Contact person for public queries
Name 60531 0
Andreas Schibler
Address 60531 0
Lady Cilento Children's Hospital
501 Stanley St
South Brisbane Qld 4101
Country 60531 0
Australia
Phone 60531 0
+617 3068 5733
Fax 60531 0
Email 60531 0
[email protected]
Contact person for scientific queries
Name 60532 0
Andreas Schibler
Address 60532 0
Lady Cilento Children's Hospital
501 Stanley St
South Brisbane Qld 4101
Country 60532 0
Australia
Phone 60532 0
+617 3068 5733
Fax 60532 0
Email 60532 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 documents for sharing with this pilot study. This is a feasibility study which informed us for the larger RCT which is currently taking place (ACTRN12618000210279)


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
EmbaseNasal High Flow in Room Air for Hypoxemic Bronchiolitis Infants.2019https://dx.doi.org/10.3389/fped.2019.00426
EmbaseHigh flow in children with respiratory failure: A randomised controlled pilot trial - A paediatric acute respiratory intervention study.2021https://dx.doi.org/10.1111/jpc.15259
N.B. These documents automatically identified may not have been verified by the study sponsor.