Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12623000835640p
Ethics application status
Submitted, not yet approved
Date submitted
22/06/2023
Date registered
4/08/2023
Date last updated
4/08/2023
Date data sharing statement initially provided
4/08/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
INFINITE: A Phase II Randomised Crossover Trial to Assess Feasibility of Domiciliary Nasal High Flow for Chronic Breathlessness in People with Interstitial Lung Disease
Scientific title
A Phase II Randomised Crossover Trial to Assess Feasibility of Domiciliary Nasal High Flow for Chronic Breathlessness in People with Interstitial Lung Disease
Secondary ID [1] 309957 0
None
Universal Trial Number (UTN)
Trial acronym
INFINITE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
interstitial lung disease 330440 0
Condition category
Condition code
Respiratory 327287 327287 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Nasal High Flow (NHF) therapy is a non-invasive respiratory support device that delivers heated (32-37C) humidified, high flow (20-60 L/min) air through specialised nasal cannulae, with airflow generated from a flow generator system (myAirvoTM 3 system).

All participants will have a baseline assessment performed at a single time point (measured once between Day -13 to Day 0). Baseline assessment will include a remote sleep study with a WatchPAT monitoring device, Respirasense respiratory monitoring device, and the Global Sleep Assessment Questionnaire (GSAQ), to be conducted in the patient’s home.

Participants will then be randomly allocated according to the randomisation procedure to either:

o Arm 1 – NHF therapy for 4 weeks, followed by usual care for 4 weeks with a one-week washout between periods.
o Arm 2 – Usual care for 4 weeks, followed by NHF therapy for 4 weeks with a one-week washout between periods.

At the start of the NHF Therapy intervention period, a respiratory nurse will commence the initial use of the intervention of NHF either in a study site (clinic) or home setting. There are no current published guidelines on NHF titration, and this will be individualised to each participant by a skilled senior respiratory clinical nurse. No oxygen will be entrained as eligible participants will not have severe resting hypoxemia based on SpO2 assessment at rest (SpO2 equal to or greater than 92%).

Patients will be contacted at regular intervals (on day 3 of each treatment period and then every week for the remainder of the treatment period) during both the NHF therapy period and usual care period to troubleshoot device usage, prompt completion of daily VAS scores, and monitor adverse events. Participants will be able to telephone the respiratory nurse at other times for any device issues on a non-urgent basis (within 1 business day; as per current usual practice with home respiratory supports). From a safety perspective discontinuing either NHF without oxygen entrained does not have significant clinical consequences. NHF use will be recommended for 7 hours over 24 hours (ideally overnight). Current medications can continue. Rescue medications if used will be monitored.

Patient reported outcomes will be assessed at the end of each 4-week period. Participants will be invited to participate in a semi-structured interview about their experiences with NHF at the conclusion of their NHF therapy period (either during the washout week or during the follow-up week dependent on randomisation).
Intervention code [1] 326375 0
Treatment: Devices
Comparator / control treatment
Standard care, dependant on clinical indication, including but not limited to:

- pulmonary rehabilitation
- optimisation of medical therapy
- self-management education
- exacerbation action plans (if appropriate)
- education and provision of a breathlessness plan regarding non-pharmacological approaches to managing breathlessness: activity pacing, positions to ease breathlessness, breathing techniques and the use of the handheld fan
- low dose opioids for breathlessness if clinically indicated
Control group
Active

Outcomes
Primary outcome [1] 335164 0
The primary outcome for this study is feasibility as determined by the composite number of participants who have been screened, met eligibility criteria, enrolled, randomised and completed the study. Data will be sourced from screening, enrolment, and withdrawal logs. Completion is defined as completing the final assessment.
Timepoint [1] 335164 0
12 months after trial start date
Secondary outcome [1] 423328 0
Between-treatment difference in change from baseline to end-of-treatment scores in breathlessness (dyspnoea), measured by 100mm Visual Analogue Score (VAS; using a 3-day average daily score at baseline relative to 3-day average daily score at end of treatment period)
Timepoint [1] 423328 0
Day 63 post-commencement of intervention
Secondary outcome [2] 423329 0
Between-treatment difference in change from baseline to end-of-treatment scores, in breathlessness (dyspnoea), measured by Dyspnea-12 (D12)
Timepoint [2] 423329 0
Day 63 post-commencement of intervention
Secondary outcome [3] 423330 0
Between-treatment difference in change from baseline to end-of-treatment scores, in breathlessness (dyspnoea), measured by Chronic Respiratory Disease Questionnaire Self-Administered Standardised – Mastery domain (CRQ-M)
Timepoint [3] 423330 0
Day 63 post-commencement of intervention
Secondary outcome [4] 423331 0
between-treatment difference in change from baseline to end-of-treatment scores, in respiratory rate, as measured by non-invasive device worn on the chest (Respirasense®)
Timepoint [4] 423331 0
Day 63 post-commencement of intervention
Secondary outcome [5] 423333 0
between-treatment difference in change from baseline to end-of-treatment scores, in respiratory rate, as measured by non-contact under mattress monitoring mat (VitalDetect-Bed)
Timepoint [5] 423333 0
Day 63 post-commencement of intervention
Secondary outcome [6] 423334 0
between-treatment difference in change from baseline to end-of-treatment scores, in oxygen saturation, as measured by non-invasive device worn on the finger (Nonin®)
Timepoint [6] 423334 0
Day 63 post-commencement of intervention
Secondary outcome [7] 423335 0
between-treatment difference in change from baseline to end-of-treatment scores, in health-related quality of life, measured by as measured by King’s Brief Interstitial Lung Disease (KBILD)
Timepoint [7] 423335 0
Day 63 post-commencement of intervention
Secondary outcome [8] 423336 0
between-treatment difference in change from baseline to end-of-treatment scores, in cough, measured by as measured by Leicester Cough Questionnaire (LCQ)
Timepoint [8] 423336 0
Day 63 post-commencement of intervention
Secondary outcome [9] 423337 0
between-treatment difference in change from baseline to end-of-treatment scores, in activity levels, as measured by tri-axial activity monitor (Garmin)
Timepoint [9] 423337 0
Day 63 post-commencement of intervention
Secondary outcome [10] 423338 0
between-treatment difference in change from baseline to end-of-treatment scores, in fatigue, measured by as measured by Functional Assessment of Chronic Illness Therapy – Fatigue scale version 4 (FACIT-Fatigue)
Timepoint [10] 423338 0
Day 63 post-commencement of intervention
Secondary outcome [11] 423340 0
between-treatment difference in change from baseline to end-of-treatment scores, in sleep, measured by as measured by Richard-Charles Sleep Questionnaire (RCSQ)
Timepoint [11] 423340 0
Day 63 post-commencement of intervention
Secondary outcome [12] 423341 0
between-treatment difference in change from baseline to end-of-treatment scores, in anxiety, measured by as measured by Generalised Anxiety Disorder Assessment (GAD-7)
Timepoint [12] 423341 0
Day 63 post-commencement of intervention
Secondary outcome [13] 423342 0
between-treatment difference in change from baseline to end-of-treatment scores, in depression, measured by as measured by Patient Health Questionnaire (PHQ-9)
Timepoint [13] 423342 0
Day 63 post-commencement of intervention
Secondary outcome [14] 423344 0
Safety and tolerability, as measured by Adverse events. Adverse events will be assessed by regularly (at least weekly during phone call monitoring visits) prompting participants to describe any new or changed adverse events and recorded using Common Terminology Criteria for Adverse Events (CTCAE) version 5. . Previous trials of nasal high flow therapy for chronic lung disease have reported no serious adverse events or side effects. Discomfort from drying of airways may be experienced and will be managed with optimisation of device settings.
Timepoint [14] 423344 0
Day 63 post-commencement of intervention
Secondary outcome [15] 423345 0
Overall symptom control, as measured by composite of Between-treatment difference in type and frequency of rescue medications used. Rescue medications will be assessed in a paper-based daily diary where participants will record name, time, and dosage of any medications taken on an as-needed basis for control of breathlessness, including but not limited to opioids and benzodiazepines.
Timepoint [15] 423345 0
Day 63 post-commencement of intervention
Secondary outcome [16] 423346 0
Patient experiences and perceptions, as measured by thematic analysis of semi-structured interviews conducted face-to-face or remotely (via teleconference of phone call as required) with a member of the research team
Timepoint [16] 423346 0
end of the NHF treatment period (day 29 to day 35 post-commencement of NHF therapy)
Secondary outcome [17] 424283 0
between-treatment difference in change from baseline to end-of-treatment scores, in heart rate, as measured by non-contact under mattress monitoring mat (VitalDetect-Bed)
Timepoint [17] 424283 0
Day 63 post-commencement of intervention
Secondary outcome [18] 424284 0
between-treatment difference in change from baseline to end-of-treatment scores, in composite sleep parameters (nocturnal heart rate and nocturnal respiratory rate), as measured by non-contact under mattress monitoring mat (VitalDetect-Bed)
Timepoint [18] 424284 0
Day 63 post-commencement of intervention
Secondary outcome [19] 424285 0
between-treatment difference in change from baseline to end-of-treatment scores, in heart rate, as measured by tri-axial activity monitor (Garmin)
Timepoint [19] 424285 0
Day 63 post-commencement of intervention
Secondary outcome [20] 424286 0
between-treatment difference in change from baseline to end-of-treatment scores, in oxygen saturation, as measured by tri-axial activity monitor (Garmin)
Timepoint [20] 424286 0
Day 63 post-commencement of intervention
Secondary outcome [21] 424287 0
Safety and tolerability, as measured by actual device usage extracted from device analytics.
Timepoint [21] 424287 0
Day 63 post-commencement of intervention

Eligibility
Key inclusion criteria
o Age 18 years and over
o confirmed ILD as determined by:
o radiological evidence on CT chest scan (within last 5 years) or
o pulmonary function tests with DLco less than 60% and/or restrictive spirometry (within last 3 years)
o physician confirmed optimisation of treatment of ILD
o breathlessness as determined by modified medical research council dyspnea score (mMRC) greater than on equal to 2
o not currently on home, long-term, oxygen therapy for greater than or equal to 16h/day and not meeting criteria for home long-term oxygen therapy (i.e., SpO2 at rest greater than or equal to 92%)
o patients using only portable oxygen therapy on exertion remain eligible
o able to provide written informed consent
o capable of completing assessments and following the study procedures.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
o Acute exacerbation of ILD, including but not limited to:
o chest infection in the past 4 weeks (unstable)
o on home long-term oxygen therapy for greater than or equal to 16h/day
o enrolled in other clinical trials which may impact breathlessness (as determined by the study investigator)
o commenced (or required to commence during the trial) new treatment for ILD, including but not limited to, anti-fibrotic, opioids or benzodiazepines in the last 14 days
o previous adverse reaction to NHF
o clinician predicted survival less than or equal to 3 months
o pregnant or breast feeding
o current alcoholism or drug abuse
o untreated pneumothorax
o contradictions to NHF use, including
o requires home long-term oxygen therapy or non-invasive ventilation
o altered conscious state
o suspected or known base of skull fracture
o inability to maintain own airway or tolerate nasal prongs
o recent (last 30 days) nose or upper airway surgery – including transsphenoidal approach
o significant facial fractures or trauma (last 30 days)
o nasal obstruction or packing

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 sequence will be developed by trial data manager, who is not involved in study recruitment, and will be uploaded to REDCap. No trial investigators or personnel involved in participant recruitment or data collection will have access to the allocation sequence.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Treatment allocation will be in 1:1 ratio. A randomisation sequence will be developed using permuted block design (using R Studio software), stratified by intervention order (Arm 1 vs Arm 2).
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Not Applicable
Type of endpoint/s
Statistical methods / analysis
All resorts will be reported according to the CONSORT statement. Baseline characteristics will be presented by allocation using median (interquartile range) or mean (standard deviation) for continuous variables and frequency (percentage) for categorical variables. All analyses will be on an intention to treat basis with an additional per-protocol analysis performed.

There will be no adjustment for multiple secondary outcomes, however, results of secondary outcomes will be interpreted in the light of multiple comparisons and focus will be given to their clinical significance.

There is no formal statistical analysis of the primary feasibility outcome. Results will be presented descriptively.

Secondary outcomes will be expressed as between-treatment differences in change-from-baseline to end of treatment period for each secondary outcome measure. VAS daily breathlessness scores will be compared using a 3-day average at both baseline and end-of-treatment to account for missing data and daily variation.

Semi-structured interviews will be recorded and transcribed verbatim with all identifying data removed. Transcripts will be coded and synthesised thematically according to the principles of iterative thematic analysis.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
2/10/2023
Actual
Date of last participant enrolment
Anticipated
1/10/2024
Actual
Date of last data collection
Anticipated
3/12/2024
Actual
Sample size
Target
20
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 24977 0
The Alfred - Melbourne
Recruitment postcode(s) [1] 40630 0
3004 - Melbourne

Funding & Sponsors
Funding source category [1] 314133 0
Commercial sector/Industry
Name [1] 314133 0
Fisher and Paykel
Country [1] 314133 0
New Zealand
Primary sponsor type
Hospital
Name
Alfred Health
Address
55 Commercial Rd
Prahran 3004
VIC, Australia
Country
Australia
Secondary sponsor category [1] 316052 0
None
Name [1] 316052 0
Address [1] 316052 0
Country [1] 316052 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 313268 0
Alfred Health HREC
Ethics committee address [1] 313268 0
Ethics committee country [1] 313268 0
Australia
Date submitted for ethics approval [1] 313268 0
02/08/2023
Approval date [1] 313268 0
Ethics approval number [1] 313268 0

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

Contacts
Principal investigator
Name 127546 0
A/Prof Natasha Smallwood
Address 127546 0
Alfred Centre
99 Commercial Rd
Prahran 3004 VIC
Country 127546 0
Australia
Phone 127546 0
+61 3 9903 8930
Fax 127546 0
Email 127546 0
[email protected]
Contact person for public queries
Name 127547 0
Natasha Smallwood
Address 127547 0
Alfred Centre
99 Commercial Rd
Prahran 3004 VIC
Country 127547 0
Australia
Phone 127547 0
+61 3 9903 8930
Fax 127547 0
Email 127547 0
[email protected]
Contact person for scientific queries
Name 127548 0
Natasha Smallwood
Address 127548 0
Alfred Centre
99 Commercial Rd
Prahran 3004 VIC
Country 127548 0
Australia
Phone 127548 0
+61 3 9903 8930
Fax 127548 0
Email 127548 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?
All de-identified individual participant data will be available upon reasonable request to the principal investigator.
When will data be available (start and end dates)?
Raw data will be available immediately after publication upon reasonable request to the principal investigator with no end date.
Available to whom?
case-by-case basis at the discretion of Primary Sponsor
Available for what types of analyses?
case-by-case basis at the discretion of Primary Sponsor
How or where can data be obtained?
Raw data will be available upon reasonable request to the corresponding author on any publications.


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.