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Trial registered on ANZCTR


Registration number
ACTRN12622000132741
Ethics application status
Approved
Date submitted
13/12/2021
Date registered
27/01/2022
Date last updated
16/11/2023
Date data sharing statement initially provided
27/01/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
Efficacy of automatic oxygen control with non-invasive ventilation therapy in adults with resting hypoxaemia: A randomised cross-over trial
Scientific title
Efficacy of closed-loop oxygen control with non invasive ventilation therapy (NIV) in adults with resting hypoxaemia: A randomised cross-over trial
Secondary ID [1] 305974 0
Nil known
Universal Trial Number (UTN)
U1111-1272-0124
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic respiratory disease with resting hypoxaemia 324586 0
Cardiovascular disease with resting hypoxia 324926 0
Condition category
Condition code
Respiratory 322046 322046 0 0
Other respiratory disorders / diseases
Respiratory 322047 322047 0 0
Chronic obstructive pulmonary disease
Cardiovascular 322048 322048 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Non-invasive ventilation (NIV) therapies, including Bi-level spontaneous/ timed (S/T) NIV and Continuous Positive Airway Pressure (CPAP), using the Airvo 3 device with closed-loop oxygen titration and manual adjustments of the fraction of inspired oxygen (FiO2).

Participants will attend a single visit at the Medical Research Institute of New Zealand (MRINZ). During the visit, participants will complete 3 interventions in a randomised order, including Bi-level and CPAP interventions, as well as the comparator Nasal High Flow intervention. MRINZ staff delivering the interventions will be trained how to use the device. During the interventions, a study investigator will be present to observe the participant for safety, to adjust the settings of the device (described below), and to ensure the device is working correctly.

Each intervention will follow the same protocol of an initial 15-minute rest period, a 10-minute closed-loop oxygen control period, and six manual adjustments of FiO2:

During the 15-minute rest period, participants will be withdrawn from any pre-existing long term oxygen therapy, if they are receiving oxygen at baseline.

Participants will then receive 10 minutes of NIV therapy while the device is set to closed-loop control with a target peripheral oxygen saturation (SpO2) range set to 92-96%. A pulse oximeter sensor will be attached to the participant's finger, which will provide feedback to the Airvo 3 device.

After the 10 minutes of NIV with closed-loop oxygen control, FiO2 will be manually adjusted to the following settings:
1) Set FiO2 to 21%
2) Increase FiO2 to 25%
3) Increase FiO2 to 32%
4) Increase FiO2 to 45%
5) Decrease FiO2 to 25%
6) Decrease FiO2 to 21%
Participants will receive oxygen at each of these settings for 6 minutes.

For the Bi-Level S/T intervention, the device will be set at 15 cmH20 inspiratory positive airway pressure (IPAP), 5 cm expiratory positive airway pressure (EPAP), and 25°C humidity.

For the CPAP intervention, the device will be set at 10 cmH20, 25°C humidity.

There will be a rest period of at least 20 minutes between interventions.

The total duration of the study visit is expected to be 5 hours, with assessment of each the 3 intervention / control taking approximately 1 hour, and 2 hours allocated for rest periods.
Intervention code [1] 322370 0
Treatment: Devices
Comparator / control treatment
Nasal High Flow (NHF) therapy using the Airvo 3 device with closed-loop oxygen titration and manual adjustments of FiO2.

This comparator intervention follows the same protocol as the NIV interventions with respect to the rest period, closed-loop control period (SpO2 target range 92-96%) and the six FiO2 adjustments of values between 21-45%.

During NHF, the device will be set at 35 L/min and 37°C humidity
Control group
Active

Outcomes
Primary outcome [1] 329810 0
Time for SpO2 to come within target range on pulse oximetry while using closed-loop control of oxygen
Timepoint [1] 329810 0
The SpO2 will be monitored continuously using pulse oximetry during each intervention/control until the initial treatment period is complete.
Secondary outcome [1] 403911 0
Time course of SpO2 monitored using pulse oximetry during the entire closed loop control period
Timepoint [1] 403911 0
SpO2 will be continuously monitored using pulse oximetry for the entire duration of the initial treatment period
Secondary outcome [2] 403917 0
Time course of FiO2 during the closed loop control period
Timepoint [2] 403917 0
FIO2 will be continuously monitored as calculated by the Airvo3 device for the entirety of the initial treatment period
Secondary outcome [3] 403918 0
Time course of heart rate using pulse oximetry during closed loop control
Timepoint [3] 403918 0
Heart rate will be continuously monitored using pulse oximetry for the entirety of the initial treatment period
Secondary outcome [4] 403919 0
Time course of respiratory rate calculated by the Airvo3 device during closed loop control
Timepoint [4] 403919 0
Respiratory rate will be continuously monitored as sensed by the Airvo3 device until the end of initial treatment period
Secondary outcome [5] 403920 0
Time course of minute ventilation calculated by the Airvo3 device during closed loop control
Timepoint [5] 403920 0
Minute ventilation will be continuously monitored as sensed by the Airvo3 device until the end of initial treatment period
Secondary outcome [6] 403921 0
Time course of systolic blood pressure measured using a sphygmomanometer during closed loop control
Timepoint [6] 403921 0
Systolic blood pressure will be monitored at 5 minute intervals during the closed loop period
Secondary outcome [7] 403922 0
Time course of the trans-cutaneous partial pressure of carbon dioxide (PTcCO2) as sensed by capnography during the closed loop control period
Timepoint [7] 403922 0
PTcCO2 will be continuously monitored using a capnography device until the end of initial treatment period
Secondary outcome [8] 403938 0
Time course of SpO2 monitored using pulse oximetry during the entire manual FIO2 ramp phase of the treatment period
Timepoint [8] 403938 0
The SpO2 will be monitored continuously using a pulse oximeter during each intervention/control until the FIO2 ramp phase treatment period is complete.
Secondary outcome [9] 404970 0
Time course of heart rate using pulse oximetry during the entire manual FIO2 ramp phase
Timepoint [9] 404970 0
Heart rate will be continuously monitored using pulse oximetry for the entirety of the manual FIO2 ramp phase treatment period
Secondary outcome [10] 404971 0
Time course of heart rate using pulse oximetry during the entire manual FIO2 ramp phase treatment period
Timepoint [10] 404971 0
Respiratory rate will be continuously monitored as sensed by the Airvo 3 device for the entirety of the manual FIO2 ramp phase treatment period
Secondary outcome [11] 404972 0
Time course of systolic blood pressure measured using a sphygmomanometer during the entire manual FIO2 ramp phase treatment period
Timepoint [11] 404972 0
Systolic blood pressure will be monitored at 6 minute intervals using a sphygmomanometer during the manual FIO2 ramp phase treatment period
Secondary outcome [12] 404973 0
Time course of the trans-cutaneous partial pressure of carbon dioxide (PTcCO2) as sensed by capnography during the entire manual FIO2 ramp phase treatment period
Timepoint [12] 404973 0
Time course of the trans-cutaneous partial pressure of carbon dioxide (PTcCO2) as sensed by capnography during the manual FIO2 ramp phase treatment period
Secondary outcome [13] 404974 0
Time course of SpO2 monitored using a secondary pulse oximeter during the entire closed loop control period
Timepoint [13] 404974 0
SpO2 will be continuously monitored using a second pulse oximeter for the entire duration of the initial treatment period
Secondary outcome [14] 404975 0
Time course of SpO2 monitored using a secondary pulse oximeter during the entire manual FIO2 ramp phase of the treatment period
Timepoint [14] 404975 0
The SpO2 will be monitored continuously using a second pulse oximeter during each intervention/control until the manual FIO2 ramp phase treatment period is complete.

Eligibility
Key inclusion criteria
a) A doctor’s diagnosis of a chronic respiratory and/or cardiovascular disease
b) Oxygen saturation measured by pulse oximetry (SpO2) of less than or equal to 90% while breathing room air
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Age < 18 years
• Evidence of respiratory infection or colonization with multidrug resistant bacteria, Pseudomonas species, Burkholderia Cepacia or mycobacteria
• Risk of barotrauma, as assessed by the investigator
• Nasal or facial conditions precluding use of NHF or NIV
• Intracranial trauma or trans-nasal neurosurgery (within 6 weeks)
• 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

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)
Allocation is not concealed
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The randomisation schedule will be computer generated by the eCRF, based on a sequence prepared by the study statistician, who will have no role in the recruitment, study visits or data collection.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Numerical modelling has estimated the mean time to range is 2 mins with a standard deviation of 24 seconds. A sample size of 12 allows the mean time to target range to be estimated to within ±20 seconds, (95% confidence interval).

Data descriptions will include mean and standard deviation (SD) and median and inter-quartile range (IQR) and minimum to maximum of the individual treatments and their differences. A mixed linear model will be used to compare the two treatments to account for the same participants being measured twice with participant treated as a random effect and order of treatment and treatment as fixed effects.

The time course of the physiological variables (Oxygen saturation (SpO2), transcutaneous pressure carbon dioxide (PTcCO2), Heart rate (HR), respiratory rate (RR), minute ventilation (MV) and systolic blood pressure (SBP)) during closed loop control period and during each of the manual fraction of inspired oxygen (FiO2) ramp periods will be shown graphically by scatter plots of the raw and paired data with Locally Estimated Scatter Plot Smoother (LOESS) and approximate 95% confidence intervals.

For the physiological variables (SpO2, PTcCO2, HR, RR, MV and SBP) during each of the manual FiO2 ramp periods, the measurements at 6 minutes will be presented as mean and standard deviation (SD) and median and inter-quartile range (IQR) and minimum to maximum.

Comparison of the SpO2 measured with the different pulse oximeter devices/sites will be presented as a Bland–Altman plot of SpO2 (AIRVO 3) – SpO2 (other) versus the mean of SpO2 (AIRVO 3) + SpO2 (other) together with limits of agreement.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/02/2022
Actual
17/03/2022
Date of last participant enrolment
Anticipated
1/02/2023
Actual
27/07/2022
Date of last data collection
Anticipated
1/02/2023
Actual
27/07/2022
Sample size
Target
12
Accrual to date
Final
12
Recruitment outside Australia
Country [1] 24376 0
New Zealand
State/province [1] 24376 0
Wellington

Funding & Sponsors
Funding source category [1] 310315 0
Commercial sector/Industry
Name [1] 310315 0
Fisher & Paykel Healthcare
Country [1] 310315 0
New Zealand
Primary sponsor type
Commercial sector/Industry
Name
Medical Research Institute of New Zealand (MRINZ)
Address
Level 7, CSB Building Wellington Hospital Riddiford St, Newtown Wellington 6021 New Zealand
Country
New Zealand
Secondary sponsor category [1] 311438 0
None
Name [1] 311438 0
Address [1] 311438 0
Country [1] 311438 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 309978 0
Northern B Health and Disability Ethics Committee
Ethics committee address [1] 309978 0
Ministry of Health
Health and Disability Ethics Committees
PO Box 5013
Wellington 6140
Ethics committee country [1] 309978 0
New Zealand
Date submitted for ethics approval [1] 309978 0
02/12/2021
Approval date [1] 309978 0
18/02/2022
Ethics approval number [1] 309978 0
2021 FULL 11508

Summary
Brief summary
In some people with chronic lung and heart diseases, levels of oxygen in the blood can be low and we know that giving these people extra oxygen can help this problem and improve their health. Research studies have shown that it is important to give the correct amount of oxygen, as too little, or too much oxygen can be harmful. However, it can be difficult to give patients the right amount of oxygen, particularly as oxygen needs can vary over time.

Fisher & Paykel Healthcare have developed a new device that can automatically adjust the amount of oxygen it gives, depending on how much oxygen is in the blood at the time. This device can deliver an oxygen therapy called Nasal High Flow, which involves giving a mixture of air and oxygen at a high flow through small prongs that sit just inside the nostrils. When delivering Nasal High Flow, this device has been shown to be more effective at maintaining a patient's blood oxygen levels within their target range, compared to the conventional method whereby doctors and nurses manually adjust the amount of oxygen given.

The device can also deliver Non-Invasive Ventilation therapies (CPAP and Bi-level), which involve delivering pressurised air through a face mask. In CPAP mode, the device delivers continuous pressure through the mask so that the person receives the same pressure when they breathe in as when they breathe out. In the Bi-level setting, the machine delivers two different pressures: a higher pressure when the person breathes in and a lower pressure when they breathe out. The pressurised air acts on the airways and lungs to help support breathing.

This study will assess if the device can effectively provide targeted oxygen delivery during non-invasive ventilation therapies, while using its automatic oxygen control function. The information obtained from this study will also help improve the technology that the device uses to provide automatically controlled oxygen.
Trial website
Trial related presentations / publications
Public notes
Additional exclusion criterion:
- Suspected or proven infection with SARS-CoV-2 (COVID-19) will be excluded

Contacts
Principal investigator
Name 116054 0
Dr Louis Kirton
Address 116054 0
Medical Research Institute of New Zealand
Level 7, CSB Building
Wellington Hospital
Riddiford Street
Newtown
Wellington 6021
Country 116054 0
New Zealand
Phone 116054 0
+64 4 805 0147
Fax 116054 0
Email 116054 0
[email protected]
Contact person for public queries
Name 116055 0
Louis Kirton
Address 116055 0
Medical Research Institute of New Zealand
Level 7, CSB Building
Wellington Hospital
Riddiford Street
Newtown
Wellington 6021
Country 116055 0
New Zealand
Phone 116055 0
+64 4 805 0147
Fax 116055 0
Email 116055 0
[email protected]
Contact person for scientific queries
Name 116056 0
Louis Kirton
Address 116056 0
Medical Research Institute of New Zealand
Level 7, CSB Building
Wellington Hospital
Riddiford Street
Newtown
Wellington 6021
Country 116056 0
New Zealand
Phone 116056 0
+64 4 805 0147
Fax 116056 0
Email 116056 0
[email protected]

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 the published article, after deidentification (text, tables, figures and appendices) will be made available upon reasonable request
When will data be available (start and end dates)?
Until a minimum of 10 years after the date of publication
Available to whom?
Researchers who provide a methodologically sound proposal that has been approved by the study steering committee and sponsor to achieve the aims outlined in the approved proposal
Available for what types of analyses?
Analyses that follow methodologically sound proposal that has been approved by the study steering committee and sponsor to achieve the aims outlined in the approved proposal
How or where can data be obtained?
Data access is possible through a signed data access agreement and subject to approval by the principal investigator ([email protected]) and the study sponsor (james. [email protected]).


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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