Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12619000901101
Ethics application status
Approved
Date submitted
18/06/2019
Date registered
27/06/2019
Date last updated
22/06/2021
Date data sharing statement initially provided
27/06/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Automatic versus manual oxygen adjustment using a new nasal-high flow device to control blood oxygen levels in adult patients in hospital.
Scientific title
Automatic versus manual oxygen titration using a novel nasal high-flow oxygen delivery device in adults hospitalised with an acute illness: a randomised controlled trial
Secondary ID [1] 297966 0
None
Universal Trial Number (UTN)
U1111-1231-3000
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute illness requiring oxygen therapy 312373 0
Condition category
Condition code
Respiratory 310931 310931 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants randomized to the intervention will receive nasal high-flow (NHF) therapy using the NHFO2 device with automatic oxygen titration for a period of 24 hours.

Study investigators will be qualified medical doctors with a minimum of 2 years clinical experience. At the start of the study period an investigator will take a capillary blood gas. A study investigator will set up the NHFO2 device using new consumables included heating breathing tube and nasal cannula. A pulse oximeter sensor will be attached to the participant's finger which will provide feedback to the NHFO2 device. A second independent sensor and pulse oximeter will be attached to a different finger. The device will entrain oxygen from a wall oxygen outlet.

The NHFO2 device will be set to automatic oxygen titration mode with a target peripheral oxygen saturation (SpO2) between 92 and 96% or 88 and 92% as per the target set by the treating clinical team. A study investigator will set the initial inspired oxygen concentration (FiO2) to maintain SpO2 within target range. Flow will be set to 35L/min or to the same flow as used on the pre-study NHF device if the participant was already using NHF. Temperature will be set to 37°C. This can be adjusted to a minimum of 31°C, at request of the participant. FiO2 will be automatically adjusted between pre-set limits. An investigator will remain with the participant for the first 30 minutes after device set-up to ensure NHF is tolerated by the participant.

Capital and Coast District Health Board (CCDHB) nursing and medical staff will be trained by a study investigator how to use the NHFO2 device with automatic oxygen titration. Staff will be instructed how to change FiO2 limits, temperature, flow and how to respond to device alarms.

High and low SpO2 alarms will be set on the NHFO2 device and the independent pulse oximeter. Nursing staff will be instructed to record SpO2, at a frequency determined by early warning score and hospital protocol, as per routine practice. Participants will receive medical review according to the hospital’s early warning score system as per standard practice.

Participants will be withdrawn from the study in the event of a requirement for >50% FiO2 (92-96% group) or >40% FiO2 (88-92% group) or if an absolute increase from baseline of >10% FiO2 is required (both groups) at rest for > 10 minutes.

At the end of the 24 hour study period, a second capillary blood gas will be obtained by a study investigator. At this point participant’s involvement in the study will end and they will resume conventional oxygen therapy which will be applied and titrated by a doctor or nurse looking after the patient.

All other aspects of medical care will continue as usual during the study period.
Intervention code [1] 314186 0
Treatment: Devices
Comparator / control treatment
Participants randomized to the control treatment will receive nasal high-flow (NHF) therapy using the AIRVO 2 device with manual oxygen titration. AIRVO 2 with manual oxygen titration is the current standard of care with regard to NHF therapy in CCDHB.

At the start of the study period an investigator will take a capillary blood gas. A study investigator will set up the AIRVO 2 device using new consumables including heated breathing tube and nasal cannula. A pulse oximeter sensor will be attached to the participants finger which will be connected to a data logging device.

Target SpO2 will be between 92 and 96% or 88 and 92% for participants at risk of hypercapnic respiratory failure. A study investigator will set the initial FiO2 to maintain SpO2 within target range. Flow will be set to 35L/min or to the same flow as used on the pre-study NHF device if the participant was already using NHF. Temperature will be set to 37°C. This can be adjusted to a minimum of 31°C, at request of the participant. An investigator will remain with the participant for the first 30 minutes after device set-up to ensure NHF is tolerated by the participant. The device will entrain oxygen from a wall oxygen outlet.

CCDHB nursing and medical staff will be trained by a study investigator how to use the AIRVO 2 device. Staff will be instructed how to manually titrate FiO2 and adjust flow.

The logging device will not display any data (including SpO2 and heart rate) and no there will be no alarms. Nursing staff will be instructed to measure and record SpO2 using an independent pulse oximeter, at a frequency determined by NEWS and hospital protocol, as per routine practice.

Participants will receive medical review according to the hospital’s early warning score system as per standard practice.

Participants will be withdrawn from the study in the event of a requirement for >50% FiO2 (92-96% group) or >40% FiO2 (88-92% group) or if an absolute increase from baseline of >10% FiO2 is required (both groups) at rest for > 10 minutes.

At the end of the 24 hour study period, a second capillary blood gas will be obtained by a study investigator. At this point participant’s involvement in the study will end and they will resume conventional oxygen therapy which will be applied and titrated by a doctor or nurse looking after the patient.

All other aspects of medical care will continue as usual during the study period.
Control group
Active

Outcomes
Primary outcome [1] 319746 0
Proportion of study period spent with SpO2 within target range when signal IQ (SIQ) is >0.5 as recorded by the NHFO2 device (intervention group) or data logging device (control group)
Timepoint [1] 319746 0
End of 24 hour intervention period or at time of withdrawal from study.
Secondary outcome [1] 369388 0
Percentage of time spent with SpO2 greater than or equal to 2% below target range as recorded by the NHFO2 device (intervention group) or data logging device (control group) when SIQ >0.5
Timepoint [1] 369388 0
End of 24 hour intervention period or at time of withdrawal from study.
Secondary outcome [2] 369389 0
Percentage of time spent with SpO2 greater than or equal to 4% below target range as recorded by the NHFO2 device (intervention group) or data logging device (control group) when SIQ >0.5
Timepoint [2] 369389 0
End of 24 hour intervention period or at time of withdrawal from study.
Secondary outcome [3] 369390 0
Percentage of time spent with SpO2 greater than or equal to 8% below target range as recorded by the NHFO2 device (intervention group) or data logging device (control group) when SIQ >0.5
Timepoint [3] 369390 0
End of 24 hour intervention period or at time of withdrawal from study.
Secondary outcome [4] 369391 0
Percentage of time spent with SpO2 greater than or equal to 2% above target range as recorded by the NHFO2 device (intervention group) or data logging device (control group) when SIQ >0.5
Timepoint [4] 369391 0
End of 24 hour intervention period or at time of withdrawal from study.
Secondary outcome [5] 369392 0
Percentage of time spent with SpO2 greater than or equal to 4% above target range as recorded by the NHFO2 device (intervention group) or data logging device (control group) when SIQ >0.5
Timepoint [5] 369392 0
End of 24 hour intervention period or at time of withdrawal from study.
Secondary outcome [6] 369393 0
Percentage of time spent with SpO2 within target range during mobilisation as recorded by the NHFO2 device (intervention group) or data logging device (control group)
Timepoint [6] 369393 0
End of 24 hour intervention period or at time of withdrawal from study.
Secondary outcome [7] 369394 0
Mean heart rate as recorded by the NHFO2 device (intervention group) or data logging device (control group)
Timepoint [7] 369394 0
End of 24 hour intervention period or at time of withdrawal from study.
Secondary outcome [8] 369395 0
Maximum estimated FiO2 as recorded by the NHFO2 device (intervention group) or data logging device (control group)
Timepoint [8] 369395 0
End of 24 hour intervention period or at time of withdrawal from study.
Secondary outcome [9] 369396 0
Mean estimated FiO2 as recorded by the NHFO2 device (intervention group) or data logging device (control group)
Timepoint [9] 369396 0
End of 24 hour intervention period or at time of withdrawal from study.
Secondary outcome [10] 369397 0
Minimum estimated FiO2 as recorded by the NHFO2 device (intervention group) or data logging device (control group)
Timepoint [10] 369397 0
End of 24 hour intervention period or at time of withdrawal from study.
Secondary outcome [11] 369398 0
Capillary blood gas pH
Timepoint [11] 369398 0
Measured at enrollment and at the end of 24 hour intervention period or at time of withdrawal from study.
Secondary outcome [12] 369399 0
Capillary blood gas pCO2
Timepoint [12] 369399 0
Measured at enrollment and at the end of 24 hour intervention period or at time of withdrawal from study.
Secondary outcome [13] 369400 0
Capillary blood gas pO2
Timepoint [13] 369400 0
Measured at enrollment and at the end of 24 hour intervention period or at time of withdrawal from study.
Secondary outcome [14] 369401 0
Proportion of time spent receiving oxygen therapy during the 24 hour treatment period as recorded by the NHFO2 device (intervention group) or data logging device (control group)
Timepoint [14] 369401 0
Measured at the end of 24 hour intervention period or at time of withdrawal from study.
Secondary outcome [15] 369402 0
Number of medical emergency team (MET) calls as recorded in participants medical records
Timepoint [15] 369402 0
Measured at the end of 24 hour intervention period or at time of withdrawal from study.
Secondary outcome [16] 369413 0
Length of hospital admission after enrollment as determined from the participant's medical records
Timepoint [16] 369413 0
At time of discharge from hospital
Secondary outcome [17] 369414 0
Requirement for non invasive ventilation (NIV) at any time during hospital admission after enrollment as determined by participant's medical records.
Timepoint [17] 369414 0
At time of discharge from hospital
Secondary outcome [18] 369415 0
Admission to the intensive acre unit (ICU) at any time during hospital admission after enrollment as determined by participant's medical records.
Timepoint [18] 369415 0
At time of discharge from hospital
Secondary outcome [19] 369416 0
NHFO2 device usability as determined by a study specific usability questionnaire administered to healthcare professionals using the NHFO2 device
Timepoint [19] 369416 0
Completed at the end of 24 hour intervention period or at time of withdrawal from study.
Secondary outcome [20] 370686 0
Percentage of time spent with SpO2 within target range irrespective of SIQ as recorded by the NHFO2 device (intervention group) or data logging device (control group)
Timepoint [20] 370686 0
Measured at the end of 24 hour intervention period or at time of withdrawal from study.
Secondary outcome [21] 370687 0
Percentage of time spent with SpO2 within target range when NHFO2 SIQ <0.5 (as measured by the independent pulse oximeter when SIQ >0.5 (intervention group only)
Timepoint [21] 370687 0
Measured at the end of 24 hour intervention period or at time of withdrawal from study.
Secondary outcome [22] 371370 0
Number of FiO2 adjustments made by a healthcare professional as recorded by the NHFO2 device (intervention) or data logging device (control).
Timepoint [22] 371370 0
Measured at the end of 24 hour intervention period or at time of withdrawal from study.
Secondary outcome [23] 376583 0
Percentage of time spent with SpO2 above target range and FiO2 at the lower FiO2 limit (intervention group only) as recorded by the NHFO2 device
Timepoint [23] 376583 0
Measured at the end of 24 hour intervention period or at time of withdrawal from study.
Secondary outcome [24] 376584 0
Percentage of time with SpO2 below the target range and FiO2 at the upper FiO2 limit (intervention group only) as recorded by the NHFO2 device
Timepoint [24] 376584 0
Measured at the end of 24 hour intervention period or at time of withdrawal from study.

Eligibility
Key inclusion criteria
Inclusion Criteria: Target SpO2 88-82%
1) Current inpatient under the care of a medical or surgical team
2) Expected duration of admission >24 hours from enrolment
3) Target SpO2 of 88-92% documented by clinical team
4) NHF therapy already commenced OR treating physician decision to start NHF OR requirement for greater than or equal to 1L/min low-flow oxygen


Inclusion Criteria: Target SpO2 92-96%
1) Current inpatient under the care of a medical or surgical team
2) Expected duration of admission >24 hours from enrolment
3) Target SpO2 of 92-96% documented by clinical team
4) NHF therapy already commenced OR treating physician decision to start NHF OR requirement for greater than or equal to 2L/min low-flow oxygen
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Common Exlusion Criteria:
1) Age < 18
2) Unable to tolerate a brief interruption in oxygen therapy
3) Domiciliary use of CPAP or NIV
4) Diagnosis of obstructive sleep apnoea
5) Evidence of respiratory infection or colonization with multidrug resistant bacteria, Pseudomonas species, Burkholderia Cepacia or mycobacteria
6) Haemodynamic instability (systolic blood pressure <90mmHg or requirement for vasopressor or inotropic support)
7) Patient receiving end of life care
8) Risk of barotrauma (as assessed by the investigator)
9) Nasal or facial conditions precluding use of NHF
10) Intracranial trauma or trans-nasal neurosurgery (within 6 weeks)
11) Any condition which limits the feasibility of continuous SpO2 monitoring using a finger probe such as anatomical deformity or vascular compromise.
12) Pregnancy or breastfeeding
13) Cognitive impairment or impaired consciousness precluding informed consent
14) Implanted electronic medical device (including insulin pump, pacemaker, neurostimulator and implantable cardioverter-defibrilator)
14) 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 88-92%
1) Requirement for > 35% oxygen at time of enrolment (equivalent to 4L/min low-flow oxygen)
2) Respiratory acidosis (pH <7.35 and pCO2 >45mmHg)
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.


Exclusion Criteria: Target SpO2 92-96%
1) Requirement for > 40% oxygen at time of enrolment (equivalent to 5L/min low-flow oxygen)
2) Hypercapnia (pCO2 >45mmHg) with or without acidosis
3) 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.

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 REDCap database. The treatment to which each participant is randomised will be automatically displayed by REDCap 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 randomization schedule will be computer generated by the study statistician and incorporated into the REDCap study database
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
A sample size re-estimation is planned after the initial phase of recruitment. This will occur after the first 10 enrolled participants. This initial phase of the study will be considered a pilot run-in.

The aims of the pilot run-in and subsequent analysis are:
1) To review recommendations with respect to sample size following interim statistician analysis of variance relating to the primary outcome.
2) To review data quality, specifically whether the pulse oximeter signal quality (IQ) exceeds 0.5 for an appropriate proportion of time.
3) To review recruitment rates
4) To review participant withdrawals from study including reasons for withdrawal
5) To review participant completion rates
6) To review safety and feasibility of the study ongoing
7) To review substantial proposed protocol changes ongoing
8) To review device alarms history.


The purpose of this run-in and subsequent analysis is to evaluate the quality of the data, review recruitment rate and review variance relating to the primary outcome, which may alter the required sample size. This run-in phase will also allow the safety and feasibility of continuing the study in its current format to be reviewed.

If the pilot run-in confirms a recruitment rate that is adequate and other pre-specified aims are met, the full study will proceed without modification to the protocol. If some or all of the aims are not met, the study management committee will consider modification of the protocol.
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Two previous studies have investigated the use of an oxygen delivery device with automatic titration of the delivered flow of oxygen in patients hospitalised with an acute exacerbation of COPD and hypoxaemic patients in the ED. Based upon these studies, we estimate a total sample size of 46 participants will provide 90% power to detect a 30% difference in time spent in target range between intervention and control based on an SD of 30. The sample size calculations are based on using an unpaired t-test to compare groups, equal size numbers in intervention and control groups, and a two sided Type I error rate (alpha) of 5%. Due to uncertainty whether this sample size calculation was applicable to the performance of the NHF device, a pre-specified sample size re-estimation was performed after 10 participants which indicated a revised total of 20 participants was required to provide at least 90% power to detect a 30% difference in time spent within target SpO2 range

The primary analysis will be a general linear model (ANCOVA); with predictor variables of baseline SpO2, whether the target range was in the higher or lower range, and the randomised treatment. For other continuous response variables ANCOVA will also be used. For categorical response variables logistic regression will be used.

A sensitivity analysis will also be carried out with the model as described but with an interaction term between clinician determined target range, 92-96% or 88-92%, with treatment to evaluate whether there is evidence of treatment effect modification, namely whether the treatment effect is the same across SpO2 target ranges.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
15/11/2019
Actual
9/01/2020
Date of last participant enrolment
Anticipated
1/06/2020
Actual
2/10/2020
Date of last data collection
Anticipated
2/06/2020
Actual
2/10/2020
Sample size
Target
20
Accrual to date
Final
20
Recruitment outside Australia
Country [1] 21403 0
New Zealand
State/province [1] 21403 0
Wellington

Funding & Sponsors
Funding source category [1] 302485 0
Commercial sector/Industry
Name [1] 302485 0
Fisher and Paykel Healthcare
Country [1] 302485 0
New Zealand
Primary sponsor type
Commercial sector/Industry
Name
Fisher and Paykel Healthcare
Address
15 Maurice Paykel Place, East Tamaki, Auckland, New Zealand. Auckland 2013.
Country
New Zealand
Secondary sponsor category [1] 302395 0
None
Name [1] 302395 0
None
Address [1] 302395 0
None
Country [1] 302395 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 303147 0
Northern A Health and Disability Ethics Committee
Ethics committee address [1] 303147 0
Ethics committee country [1] 303147 0
New Zealand
Date submitted for ethics approval [1] 303147 0
27/06/2019
Approval date [1] 303147 0
05/08/2019
Ethics approval number [1] 303147 0
19/NTA/93

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

Contacts
Principal investigator
Name 92638 0
Dr James Harper
Address 92638 0
Medical Research Institute of New Zealand
Level 7, Clinical Services Building
Wellington Hospital
Riddiford St, Newtown
Wellington 6021
New Zealand
Country 92638 0
New Zealand
Phone 92638 0
+64 048050232
Fax 92638 0
Email 92638 0
[email protected]
Contact person for public queries
Name 92639 0
James Harper
Address 92639 0
Medical Research Institute of New Zealand
Level 7, Clinical Services Building
Wellington Hospital
Riddiford St, Newtown
Wellington 6021
New Zealand
Country 92639 0
New Zealand
Phone 92639 0
+64 048050232
Fax 92639 0
Email 92639 0
[email protected]
Contact person for scientific queries
Name 92640 0
James Harper
Address 92640 0
Medical Research Institute of New Zealand
Level 7, Clinical Services Building
Wellington Hospital
Riddiford St, Newtown
Wellington 6021
New Zealand
Country 92640 0
New Zealand
Phone 92640 0
+64 048050232
Fax 92640 0
Email 92640 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 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 ([email protected]) and the study sponsor ([email protected])


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
EmbaseAutomatic versus manual oxygen titration using a novel nasal high-flow device in medical inpatients with an acute illness: A randomised controlled trial.2021https://dx.doi.org/10.1136/bmjresp-2020-000843
N.B. These documents automatically identified may not have been verified by the study sponsor.