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Trial registered on ANZCTR


Registration number
ACTRN12622000423718p
Ethics application status
Not yet submitted
Date submitted
14/02/2022
Date registered
14/03/2022
Date last updated
2/09/2022
Date data sharing statement initially provided
14/03/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
Automatic versus manual oxygen titration using a novel nasal high-flow oxygen delivery device in adults attending the Emergency Department: a randomised controlled trial
Scientific title
Phase IIB parallel group randomised controlled trial of the efficacy of automatic versus manual oxygen titration using a novel nasal high-flow oxygen delivery device in patients attending the emergency department
Secondary ID [1] 306154 0
Protocol number: MRINZ/21/19
Universal Trial Number (UTN)
U1111-1271-4516
Trial acronym
NHFO2: ED study
Linked study record
This study is a follow-up study of ACTRN12621000658819.

Health condition
Health condition(s) or problem(s) studied:
Adults attending the emergency department with an acute illness who require oxygen therapy 324857 0
Condition category
Condition code
Respiratory 322291 322291 0 0
Other respiratory disorders / diseases
Emergency medicine 322733 322733 0 0
Other emergency care

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants randomised to automatic oxygen titration will receive nasal high flow oxygen therapy using the Airvo 3 device for up to a maximum of 3 hours duration of oxygen treatment in the emergency department.
A study investigator will set up the Airvo 3 device and will train ED staff on how to use the device. The study investigator will be available at all times during the treatment period to support the study intervention.
The Airvo 3 device will be set to automatic titration mode with a target SpO2 between 92 and 96% or 88 and 92%. The study investigator will set the initial FiO2 to maintain SpO2 within target range. A low and high SpO2 alarm will be set to prompt protocol compliance.
In the event of a requirement for escalation of FiO2, the device will automatically increase the FiO2 to maintain SpO2 in target range. The FiO2 will only increase to the set upper FiO2 limit. When the device reaches this FiO2 upper limit, an alarm will sound. This will prompt the participant's nurse and study investigator to adjust the parameters and/or arrange medical review. In the event of a requirement for escalation of FiO2 to maintain SpO2 within the target range, and the FiO2 is increased to above the upper limit of 0.40 in those with an 88-92% target range, and above the upper FiO2 limit of 0.50 in those with a 92-96% target range, for more than 10 minutes, the participant will be withdrawn
The randomised study treatment is completed if the patient has received nasal high flow oxygen therapy using the Airvo 3 device for a maximum of 3 hours , or if randomised treatment is stopped for a clinical indication, whichever occurs first. Such indications may include the patient being weaned off oxygen therapy, transferred to an alternative method of oxygen delivery or discharged from the emergency department.
Intervention code [1] 322559 0
Treatment: Devices
Comparator / control treatment
Participants randomised to manual oxygen titration will receive nasal high flow oxygen therapy using the Airvo3 device for up to a maximum of 3 hours duration of oxygen treatment in the emergency department.
A study investigator will set up the Airvo 3 device and will train ED staff on how to use the device. The study investigator will be available at all times during the treatment period to support the study intervention.
The Airvo 3 device will be set to manual titration mode with a target SpO2 between 92 and 96% or 88 and 92%. Nursing staff will be instructed to titrate oxygen and monitor SpO2 as per standard practice. In the event of a requirement for escalation of FiO2 to maintain SpO2 within the target range, and the FiO2 is increased to above the upper limit of 0.40 in those with an 88-92% target range, and above the upper FiO2 limit of 0.50 in those with a 92-96% target range, for more than 10 minutes, the participant will be withdrawn.
The randomised study treatment is completed if the patient has received nasal high flow oxygen therapy using the Airvo 3 device for a maximum of 3 hours , or if randomised treatment is stopped for a clinical indication, whichever occurs first. Such indications may include the patient being weaned off oxygen therapy, transferred to an alternative method of oxygen delivery or discharged from the emergency department.

Control group
Active

Outcomes
Primary outcome [1] 330051 0
Percentage of time with Peripheral oxygen saturation (SpO2) in target range as recorded using the Airvo 3 device
Timepoint [1] 330051 0
End of treatment period
Secondary outcome [1] 404729 0
Percentage of total time with SpO2 below target range as recorded using the Airvo 3 device
Timepoint [1] 404729 0
End of treatment period
Secondary outcome [2] 404730 0
Percentage of total time of SpO2 above target range as recorded using the Airvo 3 device
Timepoint [2] 404730 0
End of treatment period
Secondary outcome [3] 404731 0
Percentage of total time with SpO2 less than or equal to 85% as recorded using the Airvo 3 device
Timepoint [3] 404731 0
End of treatment period
Secondary outcome [4] 404732 0
Graph of distribution of SpO2 as recorded using the Airvo 3 device
Timepoint [4] 404732 0
End of treatment period
Secondary outcome [5] 404733 0
Minimum SpO2 as recorded using the Airvo 3 device
Timepoint [5] 404733 0
End of treatment period
Secondary outcome [6] 404734 0
Maximum SpO2 as recorded using the Airvo 3 device
Timepoint [6] 404734 0
End of treatment period
Secondary outcome [7] 404735 0
Minimum Fraction of inspired oxygen (FiO2) as recorded using the Airvo 3 device
Timepoint [7] 404735 0
End of treatment period
Secondary outcome [8] 404736 0
Maximum FiO2 as recorded using the Airvo 3 device
Timepoint [8] 404736 0
End of treatment period
Secondary outcome [9] 404737 0
Mean estimated FiO2 as recorded using the Airvo 3 device
Timepoint [9] 404737 0
End of treatment period
Secondary outcome [10] 404738 0
Number of FiO2 range adjustments as recorded using the Airvo 3 device
Timepoint [10] 404738 0
End of treatment period
Secondary outcome [11] 404740 0
Maximum respiratory rate as recorded using the Airvo 3 device
Timepoint [11] 404740 0
End of treatment period
Secondary outcome [12] 404741 0
Minimum respiratory rate as recorded using the Airvo 3 device
Timepoint [12] 404741 0
End of treatment period
Secondary outcome [13] 404742 0
Mean respiratory rate as recorded using the Airvo 3 device
Timepoint [13] 404742 0
End of treatment period
Secondary outcome [14] 404743 0
Maximum heart rate as recorded using the Airvo 3 device
Timepoint [14] 404743 0
End of treatment period
Secondary outcome [15] 404744 0
Minimum heart rate as recorded using the Airvo 3 device
Timepoint [15] 404744 0
End of treatment period
Secondary outcome [16] 404745 0
Mean heart rate as recorded using the Airvo 3 device
Timepoint [16] 404745 0
End of treatment period
Secondary outcome [17] 404746 0
Proportion admitted to hospital specifically to High dependency unit (HDU) by accessing hospital records
Timepoint [17] 404746 0
End of treatment period
Secondary outcome [18] 406692 0
Proportion admitted to hospital specifically to Intensive care unit (ICU) by accessing hospital records
Timepoint [18] 406692 0
End of treatment period

Eligibility
Key inclusion criteria
Inclusion Criteria: Target SpO2 92-96%
• Target SpO2 of 92-96% appropriate (not at risk of hypercapnic respiratory failure)
• Expected duration of oxygen therapy >1 hour

Inclusion Criteria: Target SpO2 88-92%
• Target SpO2 of 88-92% appropriate (risk of hypercapnic respiratory failure)
• Expected duration of oxygen therapy >1 hour
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Common Exclusion Criteria
• Age < 18
• Haemodynamic instability (systolic blood pressure <90mmHg or requirement for vasopressor or inotropic support)
• Documented respiratory acidosis at the time of enrolment (pH <7.35 and PCO2 >45mmHg).
• Patient receiving end of life care
• Risk of barotrauma, as assessed by the investigator
• Nasal or facial conditions precluding use of NHF
• Intracranial trauma or trans-nasal neurosurgery (within 6 weeks)
• Pregnancy or breastfeeding
• Cognitive impairment or impaired consciousness precluding informed consent
• Any other condition which, at the investigator’s discretion, is believed may present a safety risk or impact the feasibility of the study or the study results

Exclusion Criteria: Target SpO2 92-96%
• Requirement for > 50% FiO2 to achieve an SpO2 between 92-96% at time of enrolment (> 8L/min Hudson mask)
• Presence of any risk factor for hypercapnic respiratory failure including: COPD, cystic fibrosis, bronchiectasis, chest wall deformity or neuromuscular disease AND investigator considers 92-96% to be an inappropriate SpO2 target.

Exclusion Criteria: Target SpO2 88-92%
• Requirement for > 40% FiO2 at time of enrolment (equivalent to 5L/min nasal prongs)

Patients with a target SpO2 range of 88-92% and compensated hypercapnia will be eligible for inclusion, however those with a respiratory acidosis will be excluded from the study.

Participants who meet all inclusion and are not excluded by the above criteria will proceed to complete a further screening intervention (see public notes for description). If the participant requires <0.24 FiO2 after this 10 minute screening intervention, the participant will be excluded.

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)
The randomisation schedule will be concealed from study investigators within the electronic study database. The treatment to which each participant is randomised will be automatically displayed by the electronic study database for each recruited participant.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Patients will be randomised in equal proportions i.e. one-to-one, to intervention and control groups. The randomisation schedule will be computer generated by the study statistician and incorporated into the electronic study database.
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
The primary analysis will be a general linear model (ANCOVA); with predictor variables of baseline FiO2, whether the target range was in the higher or lower range, and the randomised treatment. If there is a skewed distribution, a Wilcoxon rank-based method with the Hodges-Lehmann estimator for location difference and appropriate confidence intervals will be used for all outcomes relating to SpO2. Other outcomes will be analysed using ANCOVA with adjustment for baseline or by t-test where no baseline is appropriate. Mean (SD) values will be presented for normally distributed variables and median (IQR) for other variables. The intention to treat (ITT) population is those participants who receive >30 minutes oxygen therapy.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
3/10/2022
Actual
Date of last participant enrolment
Anticipated
11/08/2023
Actual
Date of last data collection
Anticipated
18/08/2023
Actual
Sample size
Target
50
Accrual to date
Final
Recruitment outside Australia
Country [1] 24481 0
New Zealand
State/province [1] 24481 0
Wellington

Funding & Sponsors
Funding source category [1] 310495 0
Commercial sector/Industry
Name [1] 310495 0
Fisher and Paykel Healthcare
Country [1] 310495 0
New Zealand
Primary sponsor type
Commercial sector/Industry
Name
Fisher and Paykel Healthcare
Address
15 Maurice Paykel Place, East Tamaki, Auckland, New Zealand 2013
Country
New Zealand
Secondary sponsor category [1] 311661 0
None
Name [1] 311661 0
Address [1] 311661 0
Country [1] 311661 0

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 310125 0
Central Health and Disability Ethics Committee
Ethics committee address [1] 310125 0
Ministry of Health
133 Molesworth Street
PO Box 5013
Wellington
6011
Ethics committee country [1] 310125 0
New Zealand
Date submitted for ethics approval [1] 310125 0
11/07/2022
Approval date [1] 310125 0
Ethics approval number [1] 310125 0

Summary
Brief summary
This study is investigating a new oxygen delivery device which automatically adjusts the amount of oxygen it gives. A finger sensor is connected to the device and continuously measures the amount of oxygen in the blood. Based on this measurement, the device can increase or decrease the amount of oxygen to keep blood oxygen levels in the correct range. The device has been developed by Fisher and Paykel Healthcare (FPH) and is called Airvo 3.

The main aim of the study is to find out whether automatic oxygen adjustment by the Airvo 3 device keeps blood oxygen levels in the correct range for a greater amount of time compared to the usual way of adjustment by doctors and nurses. We will test this over a period of 3 hours while the patients are in the emergency department.
Trial website
Trial related presentations / publications
Public notes
Participants who have provided informed consent and are found to be eligible to enroll in the trial will undergo a screening intervention. During this process participants, will be placed on the Airvo-3 device for 10 minutes in closed loop (automatic) control mode. If at the end of the 10 minute period, the delivered FiO2 is >= 0.24 participants to keep the participant inside their pre-specified SpO2 target range, they will proceed to enrolment and randomisation in the trial

Contacts
Principal investigator
Name 116562 0
Dr Louis Kirton
Address 116562 0
Medical Research Institute of New Zealand
Level 7, Clinical Services Building
Wellington Hospital
Riddiford Street Newtown
Wellington 6021
New Zealand
Country 116562 0
New Zealand
Phone 116562 0
+64226922497
Fax 116562 0
Email 116562 0
louis.kirton@mrinz.ac.nz
Contact person for public queries
Name 116563 0
Dr Louis Kirton
Address 116563 0
Medical Research Institute of New Zealand
Level 7, Clinical Services Building
Wellington Hospital
Riddiford Street Newtown
Wellington 6021
New Zealand
Country 116563 0
New Zealand
Phone 116563 0
+64226922497
Fax 116563 0
Email 116563 0
louis.kirton@mrinz.ac.nz
Contact person for scientific queries
Name 116564 0
Dr Louis Kirton
Address 116564 0
Medical Research Institute of New Zealand
Level 7, Clinical Services Building
Wellington Hospital
Riddiford Street Newtown
Wellington 6021
New Zealand
Country 116564 0
New Zealand
Phone 116564 0
+64226922497
Fax 116564 0
Email 116564 0
louis.kirton@mrinz.ac.nz

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Individual participant data that underlie the results reported in this article, after de-dentification (texts, tables, figures and appendices)
When will data be available (start and end dates)?
One year after publication until a maximum of 5 years after publication.
Available to whom?
Researchers who provide a methodologically sound proposal that has been approved by the study steering committee and sponsor.
Available for what types of analyses?
To achieve the aims outlined in the approved proposal.
How or where can data be obtained?
Through a signed data access agreement and subject to approval by the principal investigator (louis.kirton@mrinz.ac.nz) and the study sponsor (kevin.o'donnell@fphcare.co.nz)


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.