Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12625000591459
Ethics application status
Approved
Date submitted
14/05/2025
Date registered
10/06/2025
Date last updated
10/06/2025
Date data sharing statement initially provided
10/06/2025
Type of registration
Prospectively registered

Titles & IDs
Public title
A randomised controlled trial comparing the effects of in-hospital and home-based methods of adjusting non-invasive ventilation settings in people with long-term breathing failure.
Scientific title
A single-centre randomised controlled non-inferiority trial evaluating the effects of laboratory or home non-invasive ventilation (NIV) adjustment on NIV usage in people with chronic respiratory failure: Synchronise NIV@Home.
Secondary ID [1] 314260 0
MRF2032193
Universal Trial Number (UTN)
Trial acronym
Synchronise NIV@Home RCT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic hypercapnic respiratory failure 337184 0
Neuromuscular disease 337185 0
Chronic obstructive pulmonary disease 337186 0
Chest wall disease 337187 0
Chronic obstructive pulmonary disease-obstructive sleep apnoea overlap syndrome 337188 0
Obesity hypoventilation syndrome 337189 0
Condition category
Condition code
Respiratory 333599 333599 0 0
Chronic obstructive pulmonary disease
Respiratory 333600 333600 0 0
Other respiratory disorders / diseases
Public Health 333603 333603 0 0
Health service research

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
All participants will undergo a standardised daytime titration of NIV (using Vivo 45LS ventilator [Breas Medical, Massachusetts, United States of America]), followed by a four-week acclimatisation period (Week 0 to Week 4). After this period, participants who are not successfully using NIV will be randomised to one of three study arms. These participants will complete a single overnight sleep study assessment and NIV adjustments corresponding to their study arm during the adjustment period (Week 5 to Week 8). Randomised participants may undergo additional overnight sleep studies if deemed necessary by the clinician reviewing the sleep study to improve NIV usage. Participants successfully using NIV after the acclimatisation period (Week 0 to Week 4) will not be randomised and therefore will not undergo a sleep study during the adjustment period (Week 5 to Week 8). All participants will be asked to continue using NIV as prescribed during the adjustment period (Week 5 to Week 8) and the follow up period (Week 9 to Week 16). All participants will complete a home-based review of summarised overnight NIV and respiratory data (approximately 10 hours) at end-intervention (Week 16). Participants who are not randomised at Week 4 (post-recruitment) will not be included in the primary analysis. All participants (randomised and non-randomised participants) will be included in an observational analysis (lower grade of evidence) comparing outcomes at end-intervention (Week 16).

Arm 2: Intervention
Participants randomised to Arm 2 will complete a home-based polygraphy sleep study (approximately 10 hours), with adjustments to NIV settings based on breath-by-breath analysis. On the day of the sleep study, participants will attend a telehealth assessment with a respiratory doctor, who will make any required adjustments to the NIV mask and/or settings as deemed necessary. An experienced sleep scientist will set up the polygraphy sleep study equipment in the participant's home for the participant to wear and sleep with overnight. Measurements will include thoracic and abdominal respibands, continuous oxygen saturation (SpO2) using a pulse oximeter with a finger probe, and transcutaneous carbon dioxide (PtcCO2) using transcutaneous capnography. Mask pressure, total flow, tidal volume and leak will be measured by the NIV device. The sleep study data will be analysed by experienced clinicians to determine optimal NIV settings based on breath-by-breath analysis within 72 hours of the sleep study. The optimal NIV settings will be applied and sleep study equipment will be collected during a home-visit session with a respiratory nurse.

Arm 3: Intervention
Participants randomised to Arm 3 will complete a home-based review of summarised overnight NIV and respiratory data (approximately 10 hours). On the day of the review, participants will attend a telehealth assessment with a respiratory doctor, who will make any required adjustments to the NIV mask and/or settings as deemed necessary. Participants will set up continuous SpO2 monitoring themselves using a pulse oximeter with a finger probe. Mask pressure, total flow, tidal volume and leak will be measured by the NIV device. Experienced clinicians will determine optimal NIV settings based on summarised, whole-night NIV data, analysed within 72 hours of NIV data collection. The optimal NIV settings will be applied through a second telehealth session with a respiratory nurse.
Intervention code [1] 330871 0
Treatment: Other
Comparator / control treatment
Arm 1: Intervention
Participants randomised to Arm 1 will complete a polysomnography sleep study (approximately 10 hours) in an in-hospital sleep laboratory and adjustments to NIV settings will be based on breath-by-breath analysis. On the day of the sleep study, participants will be reviewed in person by a respiratory doctor, who will make any required adjustments to the NIV mask and/or settings as deemed necessary. An experienced sleep scientist will set up the polysomnography sleep study equipment in the in-hospital sleep laboratory for the participants to wear and sleep with overnight. Measurements will include electroencephalography (EEG) using seven electrodes, left and right electrooculography (EOG), submental and diaphragm electromyography (EMG), body position, thoracic and abdominal respibands, continuous SpO2 monitoring using a pulse oximeter with a finger probe, and PtcCO2 using transcutaneous capnography. Mask pressure, total flow, tidal volume and leak will be measured by the NIV device. The sleep study data will be analysed by experienced clinicians to determine optimal NIV settings based on a breath-by-breath analysis within 72 hours of the sleep study. The sleep study will be staged and scored as per published criteria (The American Academy of Sleep Medicine [AASM] Manual for the Scoring of Sleep and Associated Events: Version 3.0). The optimal NIV settings will be applied through a second telehealth session with a respiratory nurse.
Control group
Active

Outcomes
Primary outcome [1] 341181 0
NIV usage
Timepoint [1] 341181 0
Week 4, Week 8, Week 12 and Week 16 (primary end-point) post initial daytime titration of NIV.
Secondary outcome [1] 446664 0
NIV treatment failure
Timepoint [1] 446664 0
Week 4 and Week 16 post initial daytime titration of NIV.
Secondary outcome [2] 446665 0
Control of Respiratory Failure on therapy
Timepoint [2] 446665 0
Week 16 post-initial daytime titration of NIV.
Secondary outcome [3] 446666 0
Dyspnoea
Timepoint [3] 446666 0
Week 0, Week 4 and Week 16 post-initial daytime titration of NIV.
Secondary outcome [4] 446667 0
Dyspnoea
Timepoint [4] 446667 0
Week 0, Week 4 and Week 16 post-initial daytime titration of NIV.
Secondary outcome [5] 446668 0
Health-related quality of life
Timepoint [5] 446668 0
Week 0 and Week 16 post-initial daytime titration of NIV.
Secondary outcome [6] 446671 0
Health-related quality of life
Timepoint [6] 446671 0
Week 0 and Week 16 post-initial daytime titration of NIV.
Secondary outcome [7] 446672 0
Sleep quality
Timepoint [7] 446672 0
Week 0, Week 4 and Week 16 post-initial daytime titration of NIV.
Secondary outcome [8] 446675 0
Daytime somnolence
Timepoint [8] 446675 0
Week 0, Week 4 and Week 16 post-initial daytime titration of NIV.
Secondary outcome [9] 446676 0
Daytime somnolence
Timepoint [9] 446676 0
Week 0, Week 4 and Week 16 post-initial daytime titration of NIV.
Secondary outcome [10] 446677 0
Comfort on ventilator
Timepoint [10] 446677 0
Week 4, Week 8, Week 12 and Week 16 post-initial daytime titration of NIV.
Secondary outcome [11] 446678 0
Time to analysis method
Timepoint [11] 446678 0
Cumulative data will be assessed at the conclusion of the trial.
Secondary outcome [12] 446679 0
Time to setting adjustment
Timepoint [12] 446679 0
Cumulative data will be assessed at the conclusion of the trial.
Secondary outcome [13] 446684 0
Successful recording of ventilator and monitoring data.
Timepoint [13] 446684 0
Cumulative data will be assessed at the conclusion of the trial.
Secondary outcome [14] 446685 0
Resource requirements for analysis method
Timepoint [14] 446685 0
Cumulative data will be assessed at the conclusion of the trial.
Secondary outcome [15] 446686 0
Contact between staff and participants
Timepoint [15] 446686 0
Cumulative data will be assessed at the conclusion of the trial.
Secondary outcome [16] 446687 0
Adverse events
Timepoint [16] 446687 0
Recorded monthly from enrolment until Week 16 post-randomisation and when sleep studies are analysed.
Secondary outcome [17] 446688 0
Resource usage costs
Timepoint [17] 446688 0
Cumulative data will be assessed at the conclusion of the trial.
Secondary outcome [18] 446689 0
Healthcare utilisation
Timepoint [18] 446689 0
Week 4, Week 8, Week 12, Week 16 post-initial daytime titration of NIV.
Secondary outcome [19] 447486 0
To understand the acceptability of the interventions and the implementation of the interventions from the perspective of patient participants
Timepoint [19] 447486 0
Once only between week 16-20 post-initial daytime titration of NIV.
Secondary outcome [20] 447487 0
To understand the acceptability of the interventions and the implementation of the interventions from the perspective of clinicians who delivered the interventions.
Timepoint [20] 447487 0
End of trial or cessation of employment in the trial
Secondary outcome [21] 448143 0
Control of Respiratory Failure on therapy
Timepoint [21] 448143 0
Week 16 post-initial daytime titration of NIV
Secondary outcome [22] 448163 0
Control of Respiratory Failure on therapy
Timepoint [22] 448163 0
Week 16 post-initial daytime titration of NIV
Secondary outcome [23] 448164 0
Successful recording of ventilator and monitoring data
Timepoint [23] 448164 0
Cumulative data will be assessed at the conclusion of the trial.
Secondary outcome [24] 448165 0
Successful recording of ventilator and monitoring data.
Timepoint [24] 448165 0
Cumulative data will be assessed at the conclusion of the trial.
Secondary outcome [25] 448166 0
Successful recording of ventilator and monitoring data.
Timepoint [25] 448166 0
Cumulative data will be assessed at the conclusion of the trial.
Secondary outcome [26] 448167 0
Successful recording of ventilator and monitoring data.
Timepoint [26] 448167 0
Cumulative data will be assessed at the conclusion of the trial.
Secondary outcome [27] 448168 0
To understand the feasibility of the interventions and the implementation of the interventions from the perspective of patient participants
Timepoint [27] 448168 0
Once only between week 16-20 post-initial daytime titration of NIV.
Secondary outcome [28] 448169 0
To understand the feasibility of the interventions and the implementation of the interventions from the perspective of clinicians who delivered the interventions.
Timepoint [28] 448169 0
End of trial or cessation of employment in the trial

Eligibility
Key inclusion criteria
Age > 18 years,
Medically stable,
With or at risk of chronic hypercapnic respiratory failure,
Referred to the Victorian Respiratory Support Service (Victoria, Australia),
Clinical indication to commence long term NIV according to local protocols, published guidelines, and/or specialist opinion, AND
Either suitable for day admission or short stay (<2 nights) for NIV implementation, with support to enable travel and utilise NIV in the home OR commencing long term NIV at the end of an acute admission with respiratory failure and clinically stable prior to discharge
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Medically unstable,
Hypoventilation attributable to medications with sedative/respiratory depressant side-effects,
Diagnosis of motor neurone disease,
Regular use of NIV (> 6 hours/day on average AND usage on > 50% of days) over the previous 3 months,
Geographically lives more than 2 hours from Austin Health via road,
No or inadequate support to manage home monitoring equipment or instructions to adjust therapy at home, including carer support,
No mobile network coverage,
Home visit safety risk,
Pregnancy,
Limited English language skills, OR
Inability to provide informed consent

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)
Centralised randomisation and allocation concealment will be ensured through a computer-generated algorithm (REDCap database). Allocation will be concealed from the research staff members recruiting participants as participants will be randomised four weeks (Week 4) following study recruitment (Week 0). Allocation will be concealed from the respiratory doctor who determines whether a participant requires a sleep study (Week 4, post acclimatisation period), as participants are randomised following this review by an independent research staff member.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
A computer-generated randomisation list will be provided by an independent statistician, using randomly permuted blocks. Participants will be randomised in a 1:1:1 ratio.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Assuming a SD of 132 minutes for NIV usage and to determine non-inferiority between interventions, 117 participants (39 per study group) are required to be 80% sure that the lower limit of a one-sided 95% confidence interval will be above the non-inferiority limit of -75 minutes in average daily NIV usage for the study arms (Arm 2 and 3 compared to Arm 1) at Week 16. Allowing for a 10% drop out and for 25% of participants successfully using NIV at Week 4, 172 participants will be required to be recruited at Week 0. Participants will be randomised in a 1:1:1 ratio to either Arm 1, Arm 2 or Arm 3.

Linear mixed models will be used to compare average daily usage of NIV between the study arms during the intervention, with treatment arm included as a fixed effect and participant as a random effect. Survival analysis will be used to analyse the time to achieve usage of at least 6 hour per night on average over the period of a week between each group. Generalised linear models will be used to compare the proportion of participants in each arm with treatment failure. Mixed models will be used to compare changes in other secondary outcomes between groups from weeks 5 to 16.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
23/06/2025
Actual
Date of last participant enrolment
Anticipated
24/04/2028
Actual
Date of last data collection
Anticipated
18/08/2028
Actual
Sample size
Target
172
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 27803 0
Austin Health - Austin Hospital - Heidelberg
Recruitment postcode(s) [1] 43997 0
3084 - Heidelberg

Funding & Sponsors
Funding source category [1] 318784 0
Government body
Name [1] 318784 0
Australian Government Department of Health and Aged Care, Medical Research Future Fund (MRFF)- 2023 Clinician Researchers: Applied Research in Health
Country [1] 318784 0
Australia
Primary sponsor type
Other
Name
Institute for Breathing and Sleep
Address
Country
Australia
Secondary sponsor category [1] 321223 0
Hospital
Name [1] 321223 0
Austin Health, Melbourne
Address [1] 321223 0
Country [1] 321223 0
Australia
Other collaborator category [1] 283490 0
University
Name [1] 283490 0
The University of Melbourne
Address [1] 283490 0
Country [1] 283490 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 317392 0
Austin Health Human Research Ethics Committee
Ethics committee address [1] 317392 0
Ethics committee country [1] 317392 0
Australia
Date submitted for ethics approval [1] 317392 0
18/12/2024
Approval date [1] 317392 0
14/04/2025
Ethics approval number [1] 317392 0
HREC/115209/Austin-2024

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

Contacts
Principal investigator
Name 140910 0
Prof Mark Howard
Address 140910 0
Victorian Respiratory Support Service (VRSS), Level 5, Harold Stokes Building, Austin Health 145 Studley Road Heidelberg, Victoria, 3084
Country 140910 0
Australia
Phone 140910 0
+61 03 9496 3663
Fax 140910 0
Email 140910 0
[email protected]
Contact person for public queries
Name 140911 0
Sarah Brown
Address 140911 0
Institute for Breathing and Sleep (IBAS), Level 5, Harold Stokes Building, Austin Health 145 Studley Road Heidelberg, Victoria, 3084
Country 140911 0
Australia
Phone 140911 0
+61 03 9496 3877
Fax 140911 0
Email 140911 0
[email protected]
Contact person for scientific queries
Name 140912 0
Mark Howard
Address 140912 0
Victorian Respiratory Support Service (VRSS), Level 5, Harold Stokes Building, Austin Health 145 Studley Road Heidelberg, Victoria, 3084
Country 140912 0
Australia
Phone 140912 0
+61 03 9496 3663
Fax 140912 0
Email 140912 0
[email protected]

Data sharing statement
Will the study consider sharing individual participant data?
Yes
Will there be any conditions when requesting access to individual participant data?
Persons/groups eligible to request access:
• Investigators whose proposed use of the individual participant data has been approved by an independent review committee. Data requester will need to sign a data access agreement.

Conditions for requesting access:
• Yes, conditions apply:
• Requires review on a case-by-case basis by the trial custodian, sponsor or data sharing committee
• Requires a data sharing agreement between data requester and trial custodian or sponsor
What individual participant data might be shared?
• De-identified individual participant data:
What types of analyses could be done with individual participant data?
• Sharing of de-identified individual participant data will be considered for individual patient data meta-analyses and other types of analyses on a case-by-case basis.

When can requests for individual participant data be made (start and end dates)?
From:
Data will be available beginning 18 months following publication with no end date.

To:
No end date
Where can requests to access individual participant data be made, or data be obtained directly?
• Email of trial custodian, sponsor or committee: Data can be obtained via written request to the Principal Investigator, A/Prof Mark Howard, via email ([email protected]). Approval will be granted by an independent review committee.

Are there extra considerations when requesting access to individual participant data?
No


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.