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Trial registered on ANZCTR


Registration number
ACTRN12621001678886
Ethics application status
Approved
Date submitted
19/11/2021
Date registered
8/12/2021
Date last updated
21/05/2024
Date data sharing statement initially provided
8/12/2021
Date results information initially provided
21/05/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
Feasibility and Efficacy of Nasal High Flow in Children post Extubation - Pilot phase study
Scientific title
Nasal High Flow in Children post Extubation - a randomised controlled trial (Pilot phase study)
Secondary ID [1] 305819 0
None
Universal Trial Number (UTN)
Trial acronym
PERSIST Pilot Phase
PERSIST = Post Extubation ReSpIratory SupporT in children
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Airway management 324336 0
Post extubation respiratory support 324337 0
Condition category
Condition code
Respiratory 321828 321828 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Nasal High Flow (NHF) therapy provided immediately post extubation by the bedside nursing and medical staff via nasal cannula using humidified and heated air with blended oxygen in paediatric intensive care. Duration as long as clinically indicated to provide clinically acceptable oxygenation (no minimum and maximum time frame).

Participants will be allocated to either
Moderate-risk for reintubation arm or Low-risk for reintubation arm.

Children allocated to the Low-risk reintubation arm will be commenced on standard oxygen in the Intensive Care Unit and only if they meet criteria for escalation of respiratory care will be placed on NHF. Criteria for escalation of respiratory care are (one or more criteria) : a.) Oxygen flows on standard oxygen exceed acceptable range (as per hospital standard practice), b.) Target SpO2 cannot be achieved (as per hospital threshold), c.) Severe respiratory distress, d.) PaCO2 = 60 mmHg and pH less than 7.25, e.) Increased lactate or other signs of cardiovascular compromise.

Children not requiring escalation will not be included in the comparison.

Comparison of effectiveness of NHF therapy between moderate-risk and low-risk arm will be performed.

The time spent on NHF will be monitored with the data obtained from the Australian and New Zealand Paediatric Intensive Care Registry (the registry measures precise duration of respiratory support in intensive care).
Intervention code [1] 322216 0
Treatment: Devices
Comparator / control treatment
Continuous positive airway pressure (CPAP) using a nasal or face mask and a dedicated ventilator according to standard intensive care practice delivering humidified and heated air blended with oxygen. CPAP will be applied by the bedside nursing and medical staff in the paediatric intensive care for the duration as long as clinically indicated to provide clinically acceptable oxygenation (no minimum and maximum time frame).

Participants will be allocated to either:
Moderate-risk for reintubation arm or Low-risk for reintubation arm.

Children allocated to the Low-risk reintubation arm will be commenced on standard oxygen in the intensive care unit and only if they meet criteria for escalation of respiratory care will be placed on CPAP. Criteria for escalation of respiratory care are (one or more criteria) : a.) Oxygen flows on standard oxygen exceed acceptable range (as per hospital standard practice), b.) Target SpO2 cannot be achieved (as per hospital threshold), c.) Severe respiratory distress, d.) PaCO2 = 60 mmHg and pH less than 7.25, e.) Increased lactate or other signs of cardiovascular compromise.

Children not requiring escalation will not be included in the comparison.

Comparison of effectiveness of CPAP therapy between moderate-risk and low-risk arm will performed.

The time spent on CPAP will be monitored with the data obtained from the Australian and New Zealand Paediatric Intensive Care Registry (the registry measures precise duration of respiratory support in intensive care)
Control group
Active

Outcomes
Primary outcome [1] 329592 0
Primary feasibility outcome - Enrolment of >90% of eligible patients within the duration of the pilot phase with a complete dataset for all outcome parameters in > 98% accessing the Australian and New Zealand Paediatric Intensive Care Society Registry and accessing hospital electronic medical records.
Timepoint [1] 329592 0
Measured at 72 hours post extubation accessing the Australian and New Zealand Paediatric Intensive Care Society Registry and accessing hospital electronic medical records.
Primary outcome [2] 329815 0
Candidate for primary efficiency outcome for pilot phase Moderate-Risk group - Respiratory Support Free Hours post extubation censored at 72 hours accessing the Australian and New Zealand Paediatric Intensive Care Society Registry and accessing hospital electronic medical records.
Timepoint [2] 329815 0
Measured at 72 hours post extubation accessing the Australian and New Zealand Paediatric Intensive Care Society Registry and accessing hospital electronic medical records.
Primary outcome [3] 329816 0
Candidate for primary efficiency outcome for pilot phase Low-Risk group - Respiratory Support Free Hours post extubation censored at 72 hours accessing the Australian and New Zealand Paediatric Intensive Care Society Registry and accessing hospital electronic medical records.
Timepoint [3] 329816 0
Measured at 72 hours post extubation accessing the Australian and New Zealand Paediatric Intensive Care Society Registry and accessing hospital electronic medical records.
Secondary outcome [1] 403113 0
Proportion of reintubations censored at 24 hours accessing the Australian and New Zealand Paediatric Intensive Care Society Registry and accessing hospital electronic medical records.
Timepoint [1] 403113 0
Measured at 24 hrs post extubation accessing the Australian and New Zealand Paediatric Intensive Care Society Registry and accessing hospital electronic medical records.
Secondary outcome [2] 403204 0
Proportion of reintubations censored at 72 hours accessing the Australian and New Zealand Paediatric Intensive Care Society Registry and accessing hospital electronic medical records.
Timepoint [2] 403204 0
Measured at 72 hrs post extubation accessing the Australian and New Zealand Paediatric Intensive Care Society Registry and accessing hospital electronic medical records.
Secondary outcome [3] 403205 0
Proportion of children requiring escalation of respiratory support post extubation censored at 72 hours (low risk group) accessing the Australian and New Zealand Paediatric Intensive Care Society Registry and accessing hospital electronic medical records.
Timepoint [3] 403205 0
Measured at 72 hrs post extubation (low risk group) accessing the Australian and New Zealand Paediatric Intensive Care Society Registry and accessing hospital electronic medical records.
Secondary outcome [4] 403207 0
Duration of stay in Paediatric Intensive Care Unit (PICU) accessing the Australian and New Zealand Paediatric Intensive Care Society Registry and accessing hospital electronic medical records.
Timepoint [4] 403207 0
Measured from admission to discharge from Paediatric Intensive Care Unit (PICU) accessing the Australian and New Zealand Paediatric Intensive Care Society Registry and accessing hospital electronic medical records.
Secondary outcome [5] 403208 0
Mortality number by data linkage with the Australian and New Zealand Paediatric Intensive Care (ANZPIC) Registry,
Timepoint [5] 403208 0
Measured at Paediatric Intensive Care Unit (PICU) discharge, Hospital discharge, 60 days and 180 days post extubation via Australian and New Zealand Paediatric Intensive Care (ANZPIC) Registry who links with the death registry and accessing hospital electronic medical records.
Secondary outcome [6] 403209 0
Use of sedatives post extubation - will measure mg of Benzodiazepines and mg of Opiates administered accessing hospital electronic medical records.
Timepoint [6] 403209 0
Will measure time during 72 hour period post extubation period and until discharge from ICU
Secondary outcome [7] 403210 0
COMFORT scores post extubation (using parent and bedside nurse as a proxy for children <6yrs) Assessed using an analogue visual scale.
Timepoint [7] 403210 0
Measure once at 1 hour post extubation and on new respiratory support method (Nasal High Flow or CPAP for moderate risk group).
Will measure again once during the time period 4-24 hrs post extubation.
Secondary outcome [8] 403211 0
Adverse outcomes - Death, cardiac arrest, Air leak accessing patient hospital electronic medical records and documented in accordance with the Common Terminology Criteria for Adverse Events
Timepoint [8] 403211 0
Measure continuously from time of extubation until discharge from hospital
Secondary outcome [9] 403213 0
Total duration of respiratory support for hospital admission accessing the Australian and New Zealand Paediatric Intensive Care Society Registry and accessing hospital electronic medical records.
Timepoint [9] 403213 0
Measure from extubation until discharge from paediatric intensive care accessing the Australian and New Zealand Paediatric Intensive Care Society Registry and accessing hospital electronic medical records.
Secondary outcome [10] 403952 0
Duration of stay in Hospital accessing the Australian and New Zealand Paediatric Intensive Care Society Registry and accessing hospital electronic medical records.
Timepoint [10] 403952 0
Measured from admission until discharge from hospital accessing the Australian and New Zealand Paediatric Intensive Care Society Registry and accessing hospital electronic medical records.

Eligibility
Key inclusion criteria
Inclusion Criteria for Moderate Reintubation Risk Group (MRRG)- General ICU study

All children less than 16 years of age with parental consent and one or both of the following:
• length of mechanical ventilation equal or more than 4 days
• oxygen requirement (FiO2 equal or more than 0.4) at extubation

Inclusion Criteria for Moderate Reintubation Risk Group (MRRG) - Cardiac ICU study

All children less than 16 years of age with parental consent and one or more of the following:
• RACHS equal or less than4
• all neonates post cardio-pulmonary bypass and age equal or less than 42 days (post cardiac surgery patients only) belong into MRRG
• oxygen requirement (FiO2 equal or more than 0.4) at extubation

Inclusion Criteria for Low Reintubation Risk Group (LRRG) – General ICU AND Cardiac ICU studies

All children less than 16 years of age with parental consent, who fail standard oxygen therapy and require escalation of respiratory support within the first 72 hours post extubation and one or more of the following:
• all children who do not meet either the inclusion criteria for the moderate-risk reintubation group or meet one of the exclusion criteria
• length of mechanical ventilation less than 4 days
• oxygen requirement prior at extubation (FiO2 less than 0.4)
Minimum age
0 Days
Maximum age
16 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Excluded are children who require a specific respiratory support (high-risk) or are excluded with the following conditions:
• Severe cardiac failure
• Child on home respiratory support
• Craniofacial abnormalities preventing the use of NHF or CPAP
• Underlying pathology requiring CPAP or BIPAP such as severe tracheomalacia or bronchomalacia
• Upper gastrointestinal surgery where positive airway pressure is contraindicated
• Acknowledged and agreed limitations to care (e.g., do not intubate or resuscitate) or death imminent
• Epistaxis
• Mid-facial fracture
• Previously recruited in the same trial during the same ICU admission
• RACHS 5 and 6
• Neuromuscular conditions
• Choanal atresia/severe choanal stenosis
• Anatomical or acquired airway conditions with a specific airway and respiratory management protocol

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
In both General ICU and Cardiac ICU children allocated to the moderate risk and low risk group will be randomly allocated to either NHF or CPAP prior to extubation. However, for the children allocated to the low-risk group receiving standard oxygen the allocated randomisation remains blinded post extubation and will become active only in the event when escalation of respiratory care is required.
Randomisation will be stratified in both studies by site and age (0-28 days, 29 days to 6 months, 6-24 months, 2 - 16 years).

Allocation is concealed by performing this function using the on-line randomisation tool. Staff members will firstly screen all patients to be extubated for inclusion criteria. If the patient meets inclusion criteria the staff member will then use the online randomisation tool which will provide an allocated treatment arm. This action of randomisation will occur immediately prior to extubation so that the staff can have ready the relevant post extubation respiratory support - Nasal high flow therapy or Non-invasive ventilation therapy being CPAP (Continuous positive airway pressure).
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Stratification will be by site and the following:

NHF and CPAP allocated in a ratio of 1:1
General or Cardiac ICU
Moderate or Low risk group
Age groups (0-28 days, =28 days to 6 months, 6-24 months, 2 - 16 years).

Randomisation is in aliquots of ten per parallel study arm and has been determined with the use of a simple randomisation using a randomisation table created by computer software.

Randomisation will be performed by using webpage online allocation (provided by Griffith University).
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Summary statistics will be reported descriptively as mean (standard deviation), median (25th-75th percentile) or frequency (percentage) as appropriate. For the Moderate Reintubation Risk Group, the primary outcome of respiratory support free hours censored at 72 hours post extubation we be compared between groups using median regression with treatment group included as the main effect. Effect estimate will be reported as median difference (95% confidence interval). Non-inferiority will be declared if the upper bound of the 95%CI is not greater than 6 hours. Analysis will take place using the per-protocol sample, and repeated using the intention-to-treat sample to test the sensitivity of findings. Analysis will take place using the intention-to-treat sample. Secondary outcomes measured on a binary scale will be compared using logistic regression. Secondary outcomes measured with count data will be compared using Poisson regression. Secondary outcomes measured as time-to-event outcomes will be compared using Cox proportional hazards models. Statistical significance will be set at P<0.05.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
20/12/2021
Actual
22/03/2022
Date of last participant enrolment
Anticipated
31/05/2022
Actual
23/05/2022
Date of last data collection
Anticipated
31/12/2022
Actual
23/05/2022
Sample size
Target
400
Accrual to date
Final
91
Recruitment in Australia
Recruitment state(s)
QLD,WA,VIC
Recruitment hospital [1] 21123 0
Gold Coast University Hospital - Southport
Recruitment hospital [2] 21124 0
The Royal Childrens Hospital - Parkville
Recruitment hospital [3] 21125 0
Perth Children's Hospital - Nedlands
Recruitment postcode(s) [1] 35980 0
3052 - Parkville
Recruitment postcode(s) [2] 35979 0
4215 - Southport
Recruitment postcode(s) [3] 35981 0
6009 - Nedlands

Funding & Sponsors
Funding source category [1] 310167 0
Government body
Name [1] 310167 0
National Health and Medical Research Council
Country [1] 310167 0
Australia
Funding source category [2] 310181 0
Government body
Name [2] 310181 0
Queensland Health
Country [2] 310181 0
Australia
Primary sponsor type
Government body
Name
Gold Coast Hospital and Health Services
Address
Gold Coast University Hospital
Level 2 Block E Pathology and Education Building
1 Hospital Boulevard
Southport QLD 4215
Country
Australia
Secondary sponsor category [1] 311266 0
None
Name [1] 311266 0
Address [1] 311266 0
Country [1] 311266 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 309855 0
Children’s Health Queensland Hospital and Health Service HREC
Ethics committee address [1] 309855 0
Centre for Children’s Health Research
Queensland Children’s Hospital Precinct
Level 7, 62 Graham Street
South Brisbane QLD 4101
Ethics committee country [1] 309855 0
Australia
Date submitted for ethics approval [1] 309855 0
10/10/2021
Approval date [1] 309855 0
20/11/2021
Ethics approval number [1] 309855 0
HREC/21/QCHQ/80408

Summary
Brief summary
This pilot study will provide a patient centred, pragmatic and individualised process liberating children from mechanical ventilation. The pilot phase of this study will determine feasibility of the trial protocol, randomisation, time to recruit and sample size for the larger multicentre randomised controlled trial (RCT) that will follow.
This pilot phase will determine feasibility, efficacy, clarity and agreement by investigators on protocol, and allow testing of randomisation with ability to improve all for the larger RCT.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 115622 0
A/Prof Donna Franklin
Address 115622 0
C/O
Gold Coast University Hospital
Gold Coast University Hospital Children's Critical Care Research Group
& GCUH ED Collaborative Research Group
1 Hospital Boulevard,
Southport, 4215, Qld
Country 115622 0
Australia
Phone 115622 0
+61 432059569
Fax 115622 0
Email 115622 0
donna.franklin@health.qld.gov.au
Contact person for public queries
Name 115623 0
A/Prof Donna Franklin
Address 115623 0
C/O
Gold Coast University Hospital
Gold Coast University Hospital Children's Critical Care Research Group
& GCUH ED Collaborative Research Group
1 Hospital Boulevard,
Southport, 4215, Qld
Country 115623 0
Australia
Phone 115623 0
+61 432059569
Fax 115623 0
Email 115623 0
donna.franklin@health.qld.gov.au
Contact person for scientific queries
Name 115624 0
A/Prof Donna Franklin
Address 115624 0
C/O
Gold Coast University Hospital
Gold Coast University Hospital Children's Critical Care Research Group
& GCUH ED Collaborative Research Group
1 Hospital Boulevard,
Southport, 4215, Qld
Country 115624 0
Australia
Phone 115624 0
+61 432059569
Fax 115624 0
Email 115624 0
donna.franklin@health.qld.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
This RCT is a pilot phase which will inform our group on the larger RCT we are wanting to perform across Australia and New Zealand. We need to improve the larger study based on the outcomes of this pilot phase. Hence we will be willing to share the larger RCT as will have a sound basis on the protocol and CRF.


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
No additional documents have been identified.