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Trial registered on ANZCTR


Registration number
ACTRN12618001144202
Ethics application status
Approved
Date submitted
6/07/2018
Date registered
12/07/2018
Date last updated
5/08/2019
Date data sharing statement initially provided
5/08/2019
Date results information initially provided
5/08/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
A Study to Investigate a New Oxygen Delivery Device while Walking
Scientific title
Closed-loop oxygen control using a novel nasal high flow device during a six minute walk test in participants with chronic respiratory disease.
Secondary ID [1] 292783 0
None
Universal Trial Number (UTN)
U1111-1200-6202
Trial acronym
NHFO2: 6MWT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic obstructive pulmonary disease (COPD) 308280 0
Other chronic respiratory disease (e.g. bronchiectasis and interstitial lung disease) 308281 0
Condition category
Condition code
Respiratory 307291 307291 0 0
Chronic obstructive pulmonary disease
Respiratory 307292 307292 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a study to assess the efficacy of a novel nasal high-flow oxygen delivery device (NHFO2) in participants with stable chronic respiratory disease who desaturate during a six-minute walk test (6MWT). The device is able to automatically adjust the delivered oxygen concentration to achieve a desired oxygen saturation (SpO2) range using feedback from a pulse oximeter and a closed-loop control mechanism. We have recently completed a related study designed to test and optimize the algorithm used in the closed-loop control mechanism in participants who are hypoxaemic at rest (ACTRN12617001278325).

In this study, participants with chronic respiratory disease, without resting hypoxaemia, who have been shown to desaturate <90% during a screening 6MWT will undertake three 6MWTs with the following interventions:

1) Using the NHFO2 device at a fixed inspired oxygen concentration (FiO2) of 28% at 35L/min flow
2) Using the NHFO2 device at a fixed inspired oxygen concentration (FiO2) of 21% at 35L/min flow
3) Using the NHFO2 device with FiO2 titrated by closed-loop control to maintain SpO2 92-96% at 35L/min flow

Participants will undertake each 6MWT at MRINZ. A Masimo RD SET Adt sensor will be attached to a finger, which will provide feedback to the NHFO2 device. Heart rate and SpO2 will be recorded by the NHFO2 device via the Masimo finger sensor. A Bitmos sat 801+ pulse oximeter will also record SpO2 and heart rate and via a second Masimo RD SET Adt sensor attached to a different finger. High-flow gas will be delivered by an Optiflow nasal cannula attached to a heated breathing tube. The NHFO2 device, data recording tablet, Bitmos pulse oximeter and an "A" size medical oxygen bottle will be attached to a mobile stand which will be pushed behind the participant by a study investigator during the walk test.

There will be a period of 2 minutes of monitoring prior to each intervention with the participant breathing room air and seated comfortably.

The 6MWT will then be undertaken as per ATS guidelines.

Each 6MWT can be stopped at any time at the participant’s request. In addition, as per ATS guidelines, the test will be stopped immediately for any of the following: chest pain, intolerable dyspnea, leg cramps, staggering, diaphoresis and pale or ashen appearance. Exertional activity will be stopped and supplemental oxygen will be applied by the investigator as necessary. The participant will be closely monitored to ensure recovery and normalization of physiological parameters. If the participant’s SpO2 falls to <80% during any 6MWT, that 6MWT will be terminated. Supplemental oxygen will be applied as necessary and the participant will be closely monitored to ensure SpO2 returns to baseline.

There will be a 10 minute period of monitoring after the 6MWT with the participant seated, using the same method of oxygen delivery as during the 6MWT.

The order of interventions will be random and participants will be blinded to each intervention. There will be a 60 minute rest period between each 6MWT with the participant breathing room air to allow physiological parameters to normalize and the effect of any oxygen therapy to wash out.

A study investigator will be present with the participant throughout the duration of the study. All study investigators will be fully qualified medical practitioners.
Intervention code [1] 301499 0
Treatment: Devices
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 306242 0
The difference in the proportion of time spent with SpO2 within target range (92-96%) during the 6MWT between the interventions (closed loop control vs high flow 21%, closed-loop control vs high-flow 28% and high-flow 21% vs high-flow 28%) as recorded by the NHFO2 device.
Timepoint [1] 306242 0
End of each 6MWT
Secondary outcome [1] 347966 0
SpO2: The difference in proportion of time spent <90%, <92%, >96% and >98% between the interventions (closed loop control vs high flow 21%, closed-loop control vs high-flow 28% and high-flow 21% vs high-flow 28%) during a 6MWT, as recorded by the NHFO2 device.
Timepoint [1] 347966 0
End of each 6MWT
Secondary outcome [2] 347967 0
Heart rate: The difference in maximum and mean heart rates between the interventions (closed loop control vs high flow 21%, closed-loop control vs high-flow 28% and high-flow 21% vs high-flow 28%) during a 6MWT, as recorded by the NHFO2 device.
Timepoint [2] 347967 0
End of each 6MWT
Secondary outcome [3] 347968 0
FiO2: The difference in mean estimated FiO2 between the interventions (closed loop control vs high flow 21%, closed-loop control vs high-flow 28% and high-flow 21% vs high-flow 28%) during a 6MWT, as recorded by the NHFO2 device.
Timepoint [3] 347968 0
End of each 6MWT
Secondary outcome [4] 347970 0
The difference in the proportion of time spent with SpO2 within target range during the post 6MWT monitoring period between the interventions (closed loop control vs high flow 21%, closed-loop control vs high-flow 28% and high-flow 21% vs high-flow 28%) as recorded by the NHFO2 device.
Timepoint [4] 347970 0
End of each post 6MWT monitoring period
Secondary outcome [5] 348616 0
Difference in distance walked during 6MWT between interventions (closed loop control vs high flow 21%, closed-loop control vs high-flow 28% and high-flow 21% vs high-flow 28%).
Timepoint [5] 348616 0
End of each 6MWT
Secondary outcome [6] 348617 0
Difference in change in Borg fatigue and dyspnoea score pre and post 6MWT between interventions
Timepoint [6] 348617 0
Borg fatigue and dyspnoea score will be measured:
Before each 6MWT
After each 6MWT
The difference between the scores will be calculated for each intervention
Secondary outcome [7] 348956 0
Difference between SpO2 as measured by the NHFO2 device and the Bitmos pulse oximeter during the 6MWT and the post 6MWT monitoring period.
Timepoint [7] 348956 0
16 minutes after commencement of each 6MWT

Eligibility
Key inclusion criteria
• Doctor’s diagnosis of chronic respiratory disease, such as chronic obstructive pulmonary disease (COPD), interstitial lung disease or bronchiectasis
• Age >18 years
• SpO2 <90% during 6 minute walk test, demonstrated at visit one.
• Stable respiratory state with no exacerbation in last 4 weeks
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Requirement for long term oxygen therapy (LTOT) or SpO2 <92% at rest
• Presence of any absolute or relative (at investigator discretion) contraindications to 6 minute walk test as per ATS/ERS technical standard
• Diagnosis of a notifiable disease
• Infection or colonization with multidrug resistant bacteria, Pseudomonas species, Burkholderia Cepacia or mycobacteria
• The presence of an implantable Medical Device
• 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)
The order in which the 6MWTs are performed will be randomised. The randomisation code will be built into the REDCap database for the study which will conceal allocation from the investigators. REDCap will automatically generate the order of 6MWTs for each participant.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The randomisation code will be generated by the study statistician using a computer generated sequence and a block size of six.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


Intervention assignment
Crossover
Other design features
Participants will be blinded to the settings used for the walk tests using the NHFO2 device (closed-loop oxygen control at 35L/min, fixed 21% FiO2 at 35L/min and fixed 28% FOi2 at 35L/min)
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Based on a previous study of an automatic oxygen titration system during walking in subjects with COPD, a sample size of 40 has at least 90% power at an alpha of 5% to detect a 20% difference in the percentage of time spent within the target SpO2 range.

A mixed linear model will be used to estimate the difference in the treatments to take into account repeated measures on the same participants. SAS version 9.4 will be used.

The primary comparison will be between NHFO2 with closed-loop oxygen control and 21% oxygen at high-flow.

A secondary analysis will be undertaken to determine whether there is an interaction between treatment response and disease type.

A sensitivity analysis will be performed to compare the SpO2 as recorded by the NHFO2 device and the Bitmos pulse oximeter


Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment outside Australia
Country [1] 10545 0
New Zealand
State/province [1] 10545 0
Wellington

Funding & Sponsors
Funding source category [1] 297415 0
Commercial sector/Industry
Name [1] 297415 0
Fisher and Paykel Healthcare
Address [1] 297415 0
15 Maurice Paykel Place, East Tamaki, Auckland, New Zealand. Auckland 2013.
Country [1] 297415 0
New Zealand
Primary sponsor type
Commercial sector/Industry
Name
Fisher and Paykel Healtcare
Address
15 Maurice Paykel Place, East Tamaki, Auckland, New Zealand. Auckland 2013.
Country
New Zealand
Secondary sponsor category [1] 299091 0
None
Name [1] 299091 0
Address [1] 299091 0
Country [1] 299091 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 298520 0
Northern B Health and Disability Ethics Committee
Ethics committee address [1] 298520 0
Health and Disability Ethics Committees
Ministry of Health
133 Molesworth Street
PO Box 5013
Wellington
6011
Ethics committee country [1] 298520 0
New Zealand
Date submitted for ethics approval [1] 298520 0
16/07/2018
Approval date [1] 298520 0
20/08/2018
Ethics approval number [1] 298520 0
18/NTB/124

Summary
Brief summary
Oxygen therapy is used extensively worldwide across a broad spectrum of both acute and chronic illness. The harmful effects of hypoxaemia are common knowledge, however it is becoming increasingly recognised that hyperoxia can also be harmful in a number of settings. It is therefore important that patients who receive oxygen, receive the correct amount. Adjustment of inspired oxygen is difficult and time consuming, which leads to patients spending significant portions of time with an oxygen saturation (SpO2) that is either too high or too low. This is of particular significance for patients with chronic lung disease.

NHFO2 is a novel nasal high-flow oxygen delivery device designed to automatically adjust the delivered oxygen concentration to keep SpO2 within a target range. The device delivers warmed, humidified gas at high flow through a nasal cannula. Oxygen is blended into the gas mixture to achieve a variable concentration of delivered oxygen. The device receives feedback from a pulse oximeter in order to adjust the delivered oxygen concentration to achieve a desired oxygen saturation range using a closed-loop control mechanism.

This is a single-blind, randomised, 3-way cross-over trial, involving participants with chronic respiratory disease such as chronic obstructive pulmonary disease (COPD), interstitial lung disease (ILD) and bronchiectasis. All participants will have shown a fall in SpO2 to below 90% during a 6MWT at visit one.

The primary aim of the trial is to examine the efficacy of the closed-loop feedback system in participants with chronic respiratory disorders, during a 6-minute walk test (6MWT).

The study comprises two visits; an initial visit of around 1 hour to gain informed consent and assess eligibility and a second visit of around 3 hours to undertake three 6MWT tests.

The 6MWTs will be performed
i) using NHFO2 with closed-loop oxygen control with a target SpO2 of 92-96%
ii) using NHFO2 set to deliver a fixed FiO2 of 21%
iii) using NHFO2 set to deliver a fixed FiO2 of 28%.

The order of the interventions during the three 6MWTs will be random.

The primary outcome is the difference in proportion of time spent with SpO2 92-96% during the 6MWT between the interventions.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 77338 0
Dr James Harper
Address 77338 0
Medical Research Institute of New Zealand
Level 7, Clinical Services Building,
Wellington Regional Hospital,
Newtown, Wellington 6021
Country 77338 0
New Zealand
Phone 77338 0
+64 4 805 0232
Fax 77338 0
Email 77338 0
james.harper@mrinz.ac.nz
Contact person for public queries
Name 77339 0
Dr James Harper
Address 77339 0
Medical Research Institute of New Zealand
Level 7, Clinical Services Building,
Wellington Regional Hospital,
Newtown, Wellington 6021
Country 77339 0
New Zealand
Phone 77339 0
+64 4 805 0232
Fax 77339 0
Email 77339 0
james.harper@mrinz.ac.nz
Contact person for scientific queries
Name 77340 0
Dr James Harper
Address 77340 0
Medical Research Institute of New Zealand
Level 7, Clinical Services Building,
Wellington Regional Hospital,
Newtown, Wellington 6021
Country 77340 0
New Zealand
Phone 77340 0
+64 4 805 0232
Fax 77340 0
Email 77340 0
james.harper@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-identification (text, tables, figures, and appendices).
When will data be available (start and end dates)?
One year after publication until a minimum 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 (james.harper@mrinz.ac.nz) and the study sponsor (james.revie@fphcare.co.nz)
What supporting documents are/will be available?
No other documents available
Summary results
Have study results been published in a peer-reviewed journal?
No
Other publications
Have study results been made publicly available in another format?
No
Results – basic reporting
Results – plain English summary