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Trial registered on ANZCTR


Registration number
ACTRN12622001296729
Ethics application status
Approved
Date submitted
15/09/2022
Date registered
6/10/2022
Date last updated
16/11/2023
Date data sharing statement initially provided
6/10/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
A randomised, cross over, non-inferiority trial comparing a newly engineered non-invasive ventilator to a commercially available device in patients with respiratory failure
Scientific title
A randomized, cross-over, non-inferiority study comparing differences in transcutaneous carbon dioxide between the Fisher and Paykel Airvo-3 non-invasive ventilator and a commercially available non-invasive ventilator, in patients with resolved acute hypercapnic respiratory failure.
Secondary ID [1] 307890 0
None
Universal Trial Number (UTN)
U1111-1282-5821
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Respiratory failure 327520 0
Condition category
Condition code
Respiratory 324627 324627 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The total study time will be approximately 2 hours duration with all study procedures being performed by a study investigator. At the beginning of the trial a Sentec transcutaneous monitoring device sensor will be attached to the participant's earlobe to monitor transcutaneous carbon dioxide (PtCO2) and oxygen saturations (SpO2). Blood pressure monitoring will also be attached.

Participants will rest for 15 minutes while the Sentec signal stabilises. If supplementary oxygen is required, it will be provided through the oxygen device in use prior to the study, or through a device agreed upon between the study investigator and the participants clinical team (examples include nasal canula, hudson mask and nasal high flow oxygen). The fraction of inspired oxygen (FiO2) will be titrated so that the participants' SpO2 values are within the target range of 88-92%. The FiO2 settings will remain fixed for the remainder of the trial.

The study intervention is the Airvo-3 NIV device and the study control is the Respironics V60 NIV device. Participants will be randomised to which device they receive NIV therapy through first, and then will cross over to the other device.

The first treatment period is 30 minutes of bi-level spontaneous timed non-invasive ventilation (NIV) therapy using either the intervention device or control device. A study investigator will establish the appropriate bi-level NIV settings with input from a respiratory/sleep specialist and upon review of previous therapeutic settings. If supplemental oxygen is required, it will be delivered through a port on the side of the NIV mask circuit, with the FiO2 set as the same as the FiO2 used during the initial 15 minute stabalisation period described above. The NIV mask will then be fitted by a study investigator, who will remain present to assess mask fit, intervention efficacy and adherence to the study procedures for the duration of this period.

Following the first treatment period, there will be a 30 minute washout period where the participant will receive oxygen if required, using the same oxygen delivery device and FiO2 as that used during the initial 15 minute stabilization period. The participant will remain resting throughout this period.

The second treatment period is 30 minutes of bi-level spontaneous timed non-invasive ventilation (NIV) therapy using whichever device was not used during the first treatment period. A study investigator will establish the appropriate bi-level NIV settings with input from a respiratory/sleep specialist and upon review of previous therapeutic settings. If supplemental oxygen is required, it will be delivered through a port on the side of the NIV mask circuit, with the FiO2 set as the same as the FiO2 used during the initial 15minute stabalisation period described above. The NIV mask will then be fitted by a study investigator, who will remain present to assess mask fit, intervention efficacy and adherence to the study procedures for the duration of this period.

After completing the second treatment period, participants will be changed back onto their standard oxygen delivery device with the settings as they were prior to entering the trial. The participants involvement in the trial will then be complete.
Intervention code [1] 324348 0
Treatment: Devices
Comparator / control treatment
The comparator treatment is 30 minutes of bi-level spontaneous timed NIV therapy on the Philips Respironics V60 ventilator, using the Fisher & Paykel Healthcare 950 humidifier and Nivairo full-face mask. The comparator intervention follows the procedures described in the interventional treatment section above
Control group
Active

Outcomes
Primary outcome [1] 332446 0
Mean transcutaneous CO2 (PtCO2) measured using capnography compared between the two devices.
Timepoint [1] 332446 0
The transcutaneous partial pressure of carbon dioxide (PtCO2) will be monitored continuously using capnography throughout the trial. End of treatment PtCO2 will be determined as the average of the final 5 minutes of the treatment period and will be adjusted for baseline, which will be determined as the 5-minute average preceding the treatment period.
Secondary outcome [1] 413556 0
Time course of heart rate using pulse oximetry during the intervention period
Timepoint [1] 413556 0
Heart rate will be continuously monitored using pulse oximetry for the entirety of the intervention period
Secondary outcome [2] 413557 0
Mean heart rate using pulse oximetry during each intervention
Timepoint [2] 413557 0
Mean value calculated over the final 5 minutes of each intervention
Secondary outcome [3] 413558 0
Time course of SpO2 using pulse oximetry during the intervention period
Timepoint [3] 413558 0
SpO2 will be continuously monitored using pulse oximetry for the entirety of the intervention period
Secondary outcome [4] 413559 0
Mean SpO2 using pulse oximetry during each intervention
Timepoint [4] 413559 0
Mean value calculated over the final 5 minutes of each intervention
Secondary outcome [5] 413560 0
Time course of respiratory rate as calculated by the Airvo 3 device/Philips V60 ventilator during the intervention period
Timepoint [5] 413560 0
Respiratory rate will be continuously monitored by the interventional devices for the entirety of the intervention period
Secondary outcome [6] 413561 0
Blood pressure using an automatic blood pressure monitor
Timepoint [6] 413561 0
Within the final 5 minutes of the intervention period
Secondary outcome [7] 413562 0
Symptoms of breathlessness as assessed using BORG scale for breathlessness
Timepoint [7] 413562 0
At the end of each intervention
Secondary outcome [8] 413563 0
Time course of PtCO2 using capnography during the intervention period
Timepoint [8] 413563 0
PtCO2 will be continuously monitored using capnography for the entirety of the treatment period
Secondary outcome [9] 413565 0
Proportion of participants who demonstrate a drop in PtCO2 of more than or equal to 4 mmHg measured using capnography (physiologically significant)
Timepoint [9] 413565 0
At end of each intervention
Secondary outcome [10] 413566 0
Proportion of participants who demonstrate a drop in PtCO2 of more than or equal to 8 mmHg measured using capnography (clinically significant)
Timepoint [10] 413566 0
At end of each intervention
Secondary outcome [11] 413567 0
Mean respiratory rate as calculated by the Airvo 3 device/Philips Respironics V60 ventilator during each intervention
Timepoint [11] 413567 0
Mean value calculated over the final 5 minutes of each intervention

Eligibility
Key inclusion criteria
• Hospitalised patient currently receiving care in a high dependency unit, respiratory ward or medical ward
• Has received acute NIV therapy for at least 1 hour during their hospital admission.
• No longer dependent on continuous NIV therapy (i.e. able to tolerate at least 3 hours without NIV therapy)
• Had an appropriate indication for commencing acute NIV therapy as assessed by the study investigator
• Spontaneously breathing
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Any contraindication to NIV therapy (according to use instructions: UI-900887 – AirSpiral NIV tube and chamber kit)
- Cardiac or respiratory arrest, or severe hemodynamic instability
- Unconscious, unable to breathe spontaneously, uncooperative, unresponsive or unable to remove the mask
- Upper airway obstruction, or inability to clear secretions (impaired cough or swallow reflexes, excessive reflux, epistaxis, hiatal hernia)
- Have copious secretions, at risk of nausea/vomiting, or at high risk of aspiration emesis
- Head or facial surgery, trauma, or burns
- Severe upper gastrointestinal bleeding, or barotrauma (undrained pneumothorax)
• Pregnancy
• Any other condition which, at the investigators discretion, is believed may present a safety risk, or impact the feasibility of the study or study results
• Requires ventilatory assistance for life support

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
Crossover
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
The objective is to demonstrate that the Airvo 3 NIV device is non-inferior at delivering bi-level S/T therapy when compared to a commercially available device delivering the same therapy. The non-inferiority margin for the change in PtCO2 over the intervention period compared between each ventilator will be 4 mmHg PtCO2, with an a of 0.05, and ß of 0.1 (i.e., power [1- ß) = 90%). Based on previous experience with PtCO2 in similar study populations, study investigators considered 4 mmHg to represent a minimal physiologically important difference in PtCO2, and judged that this should be used as the non-inferiority margin for the trial.

Sample size calculations:
The standard deviation of the change in PtCO2 in stable COPD patients on bi-level NIV from a previous trial differed depending on time period of the intervention, with values of 3.3, 3.7, and 4.5 mmHg. Based on the highest S.D of 4.5 mmHg, an a value of 0.05, a sample size of 13 had 90% power to detect a difference of 4 mmHg in the change of PtCO2. In recognition of the anticipated increased variability in PtCO2 of the intended study population, study investigators consider a sample size of 21 to be appropriate.

In addition, a power calculation will be performed after 8 participants to determine the number of participants required do demonstrate non-inferiority of the primary outcome. The power calculation will be performed based on a significance level of 0.05, 90% power, a standard deviation of 4.5 and a non-inferiority margin of 4 mmHg. The trial will proceed until the N determined by the power calculation is reached, and any dropouts will be replaced.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
17/10/2022
Actual
25/01/2023
Date of last participant enrolment
Anticipated
29/12/2023
Actual
Date of last data collection
Anticipated
29/12/2023
Actual
Sample size
Target
14
Accrual to date
10
Final
Recruitment outside Australia
Country [1] 24992 0
New Zealand
State/province [1] 24992 0
Wellington

Funding & Sponsors
Funding source category [1] 312165 0
Commercial sector/Industry
Name [1] 312165 0
Fisher and Paykel Healthcare
Country [1] 312165 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] 313692 0
None
Name [1] 313692 0
Address [1] 313692 0
Country [1] 313692 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 311554 0
Health and Disability Ethics Committee (next available committee))
Ethics committee address [1] 311554 0
Postal address:
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] 311554 0
New Zealand
Date submitted for ethics approval [1] 311554 0
07/10/2022
Approval date [1] 311554 0
02/11/2022
Ethics approval number [1] 311554 0
Ethics committee name [2] 314164 0
Northern A Health and Disability Ethics Committee
Ethics committee address [2] 314164 0
Ministry of Health
133 Molesworth Street
PO BOX 5013
Wellington
Ethics committee country [2] 314164 0
New Zealand
Date submitted for ethics approval [2] 314164 0
10/10/2022
Approval date [2] 314164 0
02/11/2022
Ethics approval number [2] 314164 0
2022 FULL 13450

Summary
Brief summary
The aim of this study is to demonstrate that the Airvo 3 NIV device is non-inferior at delivering bi-level spontaneous/timed non-invasive ventilation therapy when compared to a commercially available device (i.e. the Philips Respironics V60) delivering the same therapy.

Patients admitted to hospital with acute hypercapnic respiratory failure who have previously received bi-level NIV during their hospital admission will undergo bi-level NIV therapy using each of the devices in a randomised order. It is anticipated that the Airvo 3 NIV will produce a similar change in transcutaneous carbon dioxide as the Philips Respironics V60, with a non-inferior margin of less than or equal to 4 mmHg between devices.
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

A power calculation will be performed at 8 weeks after study initiation to determine the number of participants required to demonstrate non-inferiority of the primary outcome.

Contacts
Principal investigator
Name 121518 0
Dr Louis Kirton
Address 121518 0
Medical Research Institute of New Zealand
Level 7, CSB Building, Wellington Hospital
Riddiford St, Newtown, Wellington 6021
Country 121518 0
New Zealand
Phone 121518 0
+64 027 2144250
Fax 121518 0
Email 121518 0
[email protected]
Contact person for public queries
Name 121519 0
Louis Kirton
Address 121519 0
Medical Research Institute of New Zealand
Level 7, CSB Building, Wellington Hospital
Riddiford St, Newtown, Wellington 6021
Country 121519 0
New Zealand
Phone 121519 0
+64 027 2144250
Fax 121519 0
Email 121519 0
[email protected]
Contact person for scientific queries
Name 121520 0
Louis Kirton
Address 121520 0
Medical Research Institute of New Zealand
Level 7, CSB Building, Wellington Hospital
Riddiford St, Newtown, Wellington 6021
Country 121520 0
New Zealand
Phone 121520 0
+64 272144250
Fax 121520 0
Email 121520 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.