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Trial registered on ANZCTR


Registration number
ACTRN12622000433707
Ethics application status
Approved
Date submitted
21/02/2022
Date registered
17/03/2022
Date last updated
5/06/2023
Date data sharing statement initially provided
17/03/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
Time spent with oxygen levels within a safe range using the a new oxygen delivery device in automatic or manual mode in adults admitted to hospital (with or without COVID-19)
Scientific title
Automatic versus manual oxygen titration in adults admitted to hospital with or without COVID-19: a randomised controlled trial comparing time spent with oxygen levels within a target range
Secondary ID [1] 306450 0
none
Universal Trial Number (UTN)
U1111-1274-4029
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Coronavirus infectious disease 2019 (COVID-19) 325348 0
Respiratory failure 325349 0
Condition category
Condition code
Infection 322730 322730 0 0
Other infectious diseases
Respiratory 322731 322731 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants randomised to the intervention group will have their oxygen delivered by the Airvo-3 acute device using its closed loop oxygen control function. This function is capable of automatically adjusting the delivered oxygen concentration, and titrating it to a pre-specified SpO2 target range (92-96% or 88-92%). The randomised intervention will continue until 9 hours after randomisation.

A study investigator will set up the Airvo 3 acute device outside the patient’s room. The device setup will include various inputs to record SpO2, heart rate, FiO2, flow, pressures, temperature, respiratory rate, and device related technical data. This data will be downloaded at the end of the study period.

The Airvo 3 acute device will then be set to 1 of its 3 possible respiratory support modes. The choice of respiratory support mode (NHF, CPAP or Bi-Level) and settings for each mode will be prescribed by the treating clinician, with study investigator advice if required. The oxygen saturation target range will be set between either 88-92% or 92-96%. The decision around device setting, and any decisions related to changes in respiratory support mode during the trial will be at the discretion of the treating clinician.

The participant’s nurse and study investigator will then enter the patient’s room with the Airvo3 acute device. The device will be attached to the wall oxygen outlet via high pressure tubing. The device will be able to deliver a variable FiO2 within pre-set upper and lower limits, which can be adjusted by the study investigator or participants nurse.

The Airvo 3 acute device will be set to automatic oxygen titration mode with a target SpO2 between 92 and 96% or 88 and 92%. A study investigator will set the initial FiO2 to maintain SpO2 within target range. The FiO2 which maintains the participant’s SpO2 at the mid-point of each target range (94% for 92-96% group and 90% for 88-92% group) will be set as the mid-point for the appropriate FiO2 range. For example, if 30% FiO2 was required to maintain an SpO2 of 94% for a participant with a target SpO2 of 92-96%, the FiO2 range 25-35% would be selected. An investigator will remain with the participant for 15 minutes to ensure the treatment is tolerated.

The Airvo 3 acute device will display SpO2, FiO2, flow rate or machine pressure settings, and temperature which will be visible to the participant and healthcare professionals. A low SpO2 alarm will be set to 80%. The SpO2 alarm thresholds can be changed at the discretion of a treating clinician. An alarm will sound in the event of poor SpO2 signal quality or loss of SpO2 signal.

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 participants nurse and study investigator to adjust the FiO2 upper and lower limit parameters and/or arrange medical review. Mandatory medical review will occur if the required FiO2 to keep the participant in SpO2 target range exceeds 0.55 for 10 minutes. If the participant deteriorates to the extent that they require transfer to ICU then they will be withdrawn from the study. Until this point is met, participants with FiO2 requirements >0.55 will continue in the study. If a participants required FIO2 increases to >0.60 for at least 10 minutes they will be withdrawn from the study.

When mobilising, nursing staff will be instructed to disconnect the wall oxygen and connect an oxygen bottle to the Airvo 3 acute device. Oxygen therapy can be weaned and discontinued during the study period. If oxygen therapy is discontinued, the nasal cannula or NIV mask will be removed from the participant and the Airvo 3 acute device turned off. The patient remains under the care of the admitting medical team throughout the study duration, with a study investigator available for advice if necessary.

At this time, the data captured on the Airvo-3 acute device will be downloaded into a secure database, and assessed for adherence to the control treatment.

The data of patients who are withdrawn prior to the completion of the 8 hours of the 9-hour trial will be replaced by another participant but will be included in a sensitivity analysis. On reaching 9 hours post randomisation, those who require ongoing oxygen therapy will be transferred onto a hospital provided oxygen delivery device, and the study device will be removed from the room. The hospital provided device will be applied and titrated by the study investigator in liaison with the doctor and nurse responsible for the care of the patient.

At this time a Masimo RD SET® Adt sensor (Masimo Corporation, Irvine, CA) will be applied to a finger and connected to a small portable pulse oximeter (sat801+, Bitmos, Düsseldorf, Germany). All pulse oximeter alarms will be silenced and the screen concealed to avoid influencing clinical management. The participant and nursing staff will be advised that the sensor should be disconnected when mobilising, but at all other times it should remain connected. Nursing staff will be instructed to measure SpO2 using their normal ward pulse oximeters and adjust oxygen as they normally would in accordance with their normal practice. This is expected to align with the Wellington Hospital COVID-19 Respiratory Support Pathway. After 24 hours of monitoring a study investigator will remove the finger sensor and disconnect the pulse oximeter. At this time the participants involvement in the study will end and they will not be permitted to participate in the study again.
Intervention code [1] 322913 0
Treatment: Devices
Comparator / control treatment
Participants randomised to the control group will have their oxygen delivered by the Airvo-3 acute device using manual control. Manual control is the default setting for this device and involves a healthcare professional (in this case the participants nurse) manually adjusting the delivered oxygen concentration, and titrating it to a pre-specified SpO2 target range (92-96% or 88-92%). The randomised control will continue until 9 hours after randomisation.

A study investigator will set up the Airvo 3 acute device outside the patient’s room, The device setup will include various inputs to record SpO2, heart rate, FiO2, flow, pressures, temperature, respiratory rate, and device related technical data. This data will be downloaded at the end of the study period.

The Airvo 3 acute device will then be set to 1 of its 3 possible respiratory support modes. The choice of respiratory support mode (NHF, CPAP or Bi-Level) and settings for each mode will be prescribed by the treating clinician, with study investigator advice if required. The oxygen saturation target range will be set between either 88-92% or 92-96%. The decision around device setting, and any decisions related to changes in respiratory support mode during the trial will be at the discretion of the treating clinician.

The participant’s nurse and study investigator will then enter the patient’s room with the Airvo3 device. The device will be attached to the wall oxygen outlet via high pressure tubing. The nurse will be instructed to titrate oxygen and monitor SpO2 as per standard practice. (in accordance with Wellington Hospital Policy). In the event of a requirement for escalation of FiO2 to maintain SpO2 within the target range, and the FiO2 is increased to above 0.55 for 10 minutes then a mandatory medical review will occur. If the participant deteriorates to the extent that they require transfer to ICU then they will be withdrawn from the study. Until this point is met, participants with FiO2 requirements >0.55 will continue in the study. If a participants required FIO2 increases to >0.60 for at least 10 minutes they will be withdrawn from the study.

When mobilising, nursing staff will be instructed to disconnect the wall oxygen and connect an oxygen bottle to the Airvo 3 acute device. Oxygen therapy can be weaned and discontinued during the study period. If oxygen therapy is discontinued, the nasal cannula or NIV mask will be removed from the participant and the Airvo 3 acute device turned off. The patient remains under the care of the admitting medical team throughout the study duration, with a study investigator available for advice if necessary.

At this time, the data captured on the Airvo-3 acute device will be downloaded into a secure database, and assessed for adherence to the intervention treatment.

The data of patients who are withdrawn prior to the completion of 8 hours of the 9-hour trial will be replaced by another participant but will be included in a sensitivity analysis. On reaching 9 hours post randomisation, those who require ongoing oxygen therapy will be transferred onto a hospital provided oxygen delivery device, and the study device will be removed from the room. The hospital provided device will be applied and titrated by the study investigator in liaison with the doctor and nurse responsible for the care of the patient.

At this time a Masimo RD SET® Adt sensor (Masimo Corporation, Irvine, CA) will be applied to a finger and connected to a small portable pulse oximeter (sat801+, Bitmos, Düsseldorf, Germany). All pulse oximeter alarms will be silenced and the screen concealed to avoid influencing clinical management. The participant and nursing staff will be advised that the sensor should be disconnected when mobilising, but at all other times it should remain connected. Nursing staff will be instructed to measure SpO2 using their normal ward pulse oximeters and adjust oxygen as they normally would in accordance with their normal practice. After 24 hours of monitoring, a study investigator will remove the finger sensor and disconnect the pulse oximeter. At this time the participants involvement in the study will end and they will not be permitted to participate in the study again.
Control group
Active

Outcomes
Primary outcome [1] 330536 0
Percentage of time spent with SpO2 within target range, comparing closed loop oxygen control to manual oxygen control across ventilatory modes; NHF, CPAP-O2, BiLEVEL-O2
Timepoint [1] 330536 0
The SpO2 will be monitored continuously using pulse oximetry during each intervention/control until the 9 hours after randomisation
Secondary outcome [1] 406544 0
Time course of SpO2 monitored using pulse oximetry during the entire duration of the trial in both closed loop oxygen control group and manual oxygen control group
Timepoint [1] 406544 0
SpO2 will be continuously monitored using pulse oximetry until 9 hours after randomisation
Secondary outcome [2] 406545 0
Time course of FiO2 during the closed loop oxygen control groups and manual oxygen control groups
Timepoint [2] 406545 0
FIO2 will be continuously monitored as calculated by the Airvo3 device 9 hours after randomisation
Secondary outcome [3] 406546 0
The number of FiO2 adjustments made by healthcare professionals in both the closed loop oxygen control groups and manual oxygen control groups
Timepoint [3] 406546 0
Adjustments to FiO2 made by healthcare professionals will be documented until 9 hours after randomisation. This data will be automatically captured within the Airvo-3 acute device data collection system for download after the trial is complete, as well as being collected in a study-specific data capture form.
Secondary outcome [4] 406547 0
Time course of heart rate using pulse oximetry in both the closed loop oxygen control groups and manual oxygen control groups
Timepoint [4] 406547 0
Heart rate will be continuously monitored using pulse oximetry until 9 hours after randomisation.
Secondary outcome [5] 406548 0
Time course of respiratory rate calculated by the Airvo3 device in both the closed loop oxygen control groups and manual oxygen control groups
Timepoint [5] 406548 0
Respiratory rate will be continuously monitored as sensed by the Airvo3 device until 9 hours after randomisation
Secondary outcome [6] 406756 0
To establish the time spent with SpO2 within target range under standard clinical conditions using continuous pulse oximetry.
Timepoint [6] 406756 0
Percentage of time spent within target range during 24-hour follow up period receiving standard clinical care

Eligibility
Key inclusion criteria
• Supplemental oxygen requirement >= 2L/min nasal prongs for those with a target SpO2 of 92-96% appropriate (not at risk of hypercapnic respiratory failure)
• Supplemental oxygen requirement >= 1L/min nasal prongs for those with a target SpO2 of 88-92% appropriate (risk of hypercapnic respiratory failure)
• Requirement for NHF/CPAP/ Bi-level therapy as deemed appropriate by the patient’s treating clinician
• Expected duration of oxygen therapy >9 hours
• Measured for at least 8 hours of the initial 9 hour study period
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Age < 18
• Imminent (within 1 hour) need for invasive mechanical ventilation or intensive care unit support (based on treating clinician assessment)
• Haemodynamic instability (systolic blood pressure <90mmHg or requirement for vasopressor or inotropic support)
• Patient receiving end of life care
• Risk of barotrauma, as assessed by the investigator
• Nasal or facial conditions precluding use of NHF, CPAP or Bi-level
• 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

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 will be concealed with the randomisation schedule being computer generated after the initial assessment for inclusion in the trial is complete
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Random computerised sequence generation
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
Based on our previous study of closed loop control in medical inpatients receiving oxygen therapy, assuming a normal distribution is reasonable in the control group for proportion of time in range; with a mean (SD) of 71 (9) . However, the distribution of time in range for the treatment group was highly skew and in our past work we used a Mann-Whitney U test for estimating the difference in central location for the two treatments. A total sample size of 36 (18 in each of two arms) has 90% power, two-sided alpha of 5%, to detect an absolute difference in mean values of 15%, i.e. a mean value in the treatment group of 86; based on a distribution of time in range of 60% <90 (mean value of 80 in this stratum), 30% 90 to 97.5 (mean value of 95 in this stratum), and 10% >97.5 (mean value of 99 in this stratum). In our past work, which found a Hodges-Lehmann estimate of difference between two treatment arms of 24%, the distribution of the three groupings of time in range was 20%, 50%, and 30%.

Based on these calculations, we aim to recruit 62 participants, to ensure at least 90% power, two-sided alpha of 5%, to detect a clinically significant absolute difference in mean values of less than 15% in the proportion of time spent in range.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
21/03/2022
Actual
10/04/2022
Date of last participant enrolment
Anticipated
6/01/2023
Actual
17/04/2023
Date of last data collection
Anticipated
9/01/2023
Actual
18/04/2023
Sample size
Target
62
Accrual to date
Final
62
Recruitment outside Australia
Country [1] 24597 0
New Zealand
State/province [1] 24597 0
Wellington

Funding & Sponsors
Funding source category [1] 310800 0
Commercial sector/Industry
Name [1] 310800 0
Fisher and Paykel Healthcare
Country [1] 310800 0
New Zealand
Primary sponsor type
Commercial sector/Industry
Name
Fisher and Paykel Healthcare
Address
Fisher & Paykel Healthcare Limited
15 Maurice Paykel Place, East Tamaki, Auckland, 2013, New Zealand.
Country
New Zealand
Secondary sponsor category [1] 312044 0
None
Name [1] 312044 0
Address [1] 312044 0
Country [1] 312044 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 310368 0
Central Health and Disability Ethics Committee
Ethics committee address [1] 310368 0
Ministry of Health
Health and Disability Ethics Committees
PO Box 5013
Wellington 6140

Street address:
133 Molesworth Street
Thorndon
Wellington 6011
Ethics committee country [1] 310368 0
New Zealand
Date submitted for ethics approval [1] 310368 0
25/02/2022
Approval date [1] 310368 0
04/03/2022
Ethics approval number [1] 310368 0

Summary
Brief summary
This study assesses how effectively a new oxygen delivery device can keep patients with COVID-19 who require oxygen within a safe range of blood oxygen levels. The device can be used in manual mode, where the oxygen concentration delivered by the device is adjusted manually by a nurse. It can also be used in automatic mode, where the delivered oxygen concentration is adjusted automatically by the device.

Participants with COVID-19 will be randomly assigned to have the device deliver oxygen manually or automatically. It is anticipated that when the device adjusts participants oxygen levels automatically, it will keep participants oxygen levels within a safe range for a greater proportion of the study than oxygen that is adjusted manually.
Trial website
Trial related presentations / publications
Public notes
Name of Sponsor contact person: James Revie
Email: [email protected]
Profession: Clinical Research Manager
Country of residence: New Zealand

An assessment will occur at 8 weeks after study initiation. If fewer than expected cases of COVID-19 are eligible for the trial, then the trial will be opened up to allow recruitment of those without a diagnosis of COVID-19.

Contacts
Principal investigator
Name 117410 0
Dr Louis Kirton
Address 117410 0
Medical Research Institute of New Zealand
Level 7, CSB Building, Wellington Hospital
Riddiford St, Newtown, Wellington 6021
Country 117410 0
New Zealand
Phone 117410 0
+64226922497
Fax 117410 0
Email 117410 0
[email protected]
Contact person for public queries
Name 117411 0
Louis Kirton
Address 117411 0
Medical Research Institute of New Zealand
Level 7, CSB Building, Wellington Hospital
Riddiford St, Newtown, Wellington 6021
Country 117411 0
New Zealand
Phone 117411 0
+64226922497
Fax 117411 0
Email 117411 0
[email protected]
Contact person for scientific queries
Name 117412 0
Louis Kirton
Address 117412 0
Medical Research Institute of New Zealand
Level 7, CSB Building, Wellington Hospital
Riddiford St, Newtown, Wellington 6021
Country 117412 0
New Zealand
Phone 117412 0
+64226922497
Fax 117412 0
Email 117412 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
No individual participant data will be available due to commercial sensitivity


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.