Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621000044820
Ethics application status
Approved
Date submitted
29/07/2020
Date registered
18/01/2021
Date last updated
27/04/2023
Date data sharing statement initially provided
18/01/2021
Date results information initially provided
27/04/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
A Phase II Trial to Assess Feasibility of Using Nasal Cannula High Flow Therapy for Breathlessness in Participants with Chronic Obstructive Pulmonary Disease who do not qualify for domiciliary long-term oxygen therapy.
Scientific title
A Phase II Trial to Assess Feasibility of Using Nasal Cannula High Flow Therapy for Breathlessness in Participants with Chronic Obstructive Pulmonary Disease who do not qualify for domiciliary long-term oxygen therapy.
Secondary ID [1] 301070 0
none
Universal Trial Number (UTN)
Trial acronym
EAGLE - A Phase II Trial to Assess FEasibility of Using NAsal HiGh FLow for BrEathlessness in Participants with Chronic Obstructive Pulmonary Disease who do not qualify for domiciliary long-term oxygen therapy.
Linked study record

Health condition
Health condition(s) or problem(s) studied:
chronic obstructive pulmonary disease 317130 0
chronic breathlessness 317131 0
Condition category
Condition code
Respiratory 315287 315287 0 0
Chronic obstructive pulmonary disease

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 (30 - 37oC), humidified, high flow (between 2 to 60L/min) air through a specialised nasal cannula, with airflow generated from a flow generator system (AirvoTM 2 System). High-flow air mix only will be used, no oxygen will be administered.

On this single arm study, all participants will receive NHF therapy intervention.

All study participants will have assessments performed at a single timepoint at baseline (between Day -2 to Day 1).
Following this, a respiratory scientist or a nurse trained in setting up NHF will assist with the initial NHF set-up for each participant. This will be conducted in the RMH respiratory lab for out-patients or on the respiratory or palliative care wards for inpatients.
There are no current published guidelines on NHF titration. No oxygen will be entrained in the system as patients will not have severe resting hypoxaemia. The set up of NHF is individualised, however a suggested standard approach will follow the guidelines below:

0 minutes - 10 L/min - 31 degrees C
10 minutes - 15 L/min - 34 degrees C
20 minutes - 20 L/min - 37 degrees C
30 minutes - 25 L/min - 37 degrees C
40 minutes - 30 L/min - 37 degrees C
with optional increases on 5 L/min every 10 minutes up to 60 L/min

Participants will be educated on how to use NHF at home and advised to wear it for a minimum of 7 hours at night, with additional use in the day as desired.
Once set up, participants will commence the intervention on Day 1, and this will continue for 7 consecutive days until day 7. Post-intervention measures will be taken following completion of study (Day 8). Participants will be asked to participate in a semi-structured interview to explore their experiences and acceptance of NHF therapy.

Compliance will be recorded in a patient diary.
Intervention code [1] 317375 0
Treatment: Devices
Comparator / control treatment
No control group.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 323531 0
Study feasibility
Timepoint [1] 323531 0
Study enrolment of 10 participants over 6 months, with at least 80% of enrolled participants progressing to study completion
Secondary outcome [1] 382170 0
Breathlessness (best, worst, and average over last 24 hours), as measured by Breathlessness Numerical Rating Scale (NRS).
Timepoint [1] 382170 0
Baseline, Day 3, Day 5, Day 8
Secondary outcome [2] 382171 0
Quality of life, as measured by the CRQ-SAS
Timepoint [2] 382171 0
Baseline, Day 3, Day 5, Day 8
Secondary outcome [3] 382172 0
Composite outcome of function, as measured by the Resource Utilisation Groups – Activities of Daily Living (RUG-ADL) score and the Australia-modified Karnofsky Performance Scale (AKPS)
Timepoint [3] 382172 0
Baseline, Day 3, Day 5, Day 8
Secondary outcome [4] 382173 0
Sleep, as measured by the Pittsburgh Sleep Quality Index (PSQI)
Timepoint [4] 382173 0
Baseline, Day 3, Day 5, Day 8
Secondary outcome [5] 382174 0
Tolerability of using NHF, as measured by study retention (completion rate) and compliance with protocol measured by actual NHF flow, rate, humidity.
Timepoint [5] 382174 0
Tolerability will be assessed using data from study database at Baseline, Day 3, Day 5, Day 8.
Secondary outcome [6] 382175 0
Safety of NHF, as measured by the incidence of serious adverse events including hospital admission will be assessed in participant interview and data linkage to medical records. There are no specific adverse events associated with the device usage.
Timepoint [6] 382175 0
Baseline, Day 3, Day 5, Day 8
Secondary outcome [7] 382176 0
Frequency of use of rescue medications (e.g. opioids / anxiolytic), as measured by inpatient drug charts (inpatients) or medication diary (outpatients)
Timepoint [7] 382176 0
Daily during study intervention period
Secondary outcome [8] 386098 0
Sleep quality measured by minimally invasive sleep testing device worn on the wrist (watch PAT)
Timepoint [8] 386098 0
Baseline, Day 7

Eligibility
Key inclusion criteria
• Underlying diagnosis of severe COPD – evidence on pulmonary function tests performed within the last 24 months of Forced Expiratory Ratio (FER) <70% and Forced Expiratory Volume 1sec (FEV1) <50%
• Physician confirmed optimisation of treatment of underlying disease
• Breathlessness scale: Level 3 or above on the modified Medical Research Council (mMRC) dyspnoea scale (Bausewein, et al., 2007)
• Not currently using domiciliary long-term oxygen therapy at rest via a concentrator for 16 hours/day (oxygen saturations > 92% at rest). However patients who only use exertional oxygen therapy from portable oxygen cylinders for exertion induced hypoxaemia are eligible
• Able and willing to provide written informed consent
• Capable of completing assessments and complying with the study procedures
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Acute exacerbations of COPD in the past four weeks (i.e. unstable disease)
• Enrolment in other clinical trials that may impact study outcomes (e.g. trials on breathlessness, opioids, benzodiazepines)
• Commenced on opioids or benzodiazepines within the last 14 days or requiring commencement of these medications while on study. Patients who were commenced on slow or immediate release opioids or benzodiazepines >14 days prior to study enrolment may continue to use these while on study.
• Previous adverse reaction to NHF
• Clinician predicted survival less than seven days
• Pregnant or breastfeeding
• Chronic alcoholism or drug abuse
• Contraindications to NHF use:
o Requiring Non-Invasive or Invasive ventilation
o Altered level of consciousness (GCS 10 or below)
o Suspected or known base of skull fracture
o Inability to maintain own airway or unable to tolerate nasal prongs
o Recent surgery (in last 30 days) to the nose or upper airway - including pituitary surgery via a trans sphenoidal approach
o Significant facial fractures or trauma in last 30 days
o Nasal obstruction or nasal packing

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
All analyses will be conducted using descriptive statistics for the feasibility measures. The qualitative data will be analysed using a thematic approach with data coding generated iteratively.

Patient demographics/other baseline characteristics
All demographic and other baseline data including disease characteristics will be listed in detail. Summaries of categorical data will be presented as frequencies and percentages. For continuous data, mean, standard deviation, median, 25th and 75th percentiles, will be presented as summary tables.

Treatments (study treatment and compliance)
The actual dose of flow rate, humidity, and temperature received, as well as duration of use of NHF and any dose modifications will be listed and summarised.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/03/2021
Actual
1/10/2021
Date of last participant enrolment
Anticipated
30/09/2022
Actual
6/12/2022
Date of last data collection
Anticipated
10/10/2022
Actual
14/12/2022
Sample size
Target
15
Accrual to date
Final
15
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 16495 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [2] 16496 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment hospital [3] 18439 0
The Alfred - Melbourne
Recruitment postcode(s) [1] 30050 0
3000 - Melbourne
Recruitment postcode(s) [2] 30051 0
3050 - Parkville
Recruitment postcode(s) [3] 32546 0
3004 - Melbourne

Funding & Sponsors
Funding source category [1] 305457 0
Commercial sector/Industry
Name [1] 305457 0
Fisher and Paykel
Country [1] 305457 0
New Zealand
Primary sponsor type
Hospital
Name
Melbourne Health
Address
300 Grattan St, Parkville VIC 3050
Country
Australia
Secondary sponsor category [1] 305912 0
None
Name [1] 305912 0
none
Address [1] 305912 0
none
Country [1] 305912 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 305773 0
Melbourne Health HREC
Ethics committee address [1] 305773 0
300 Grattan Street (corner of Royal Parade)
Parkville, Victoria 3050
Ethics committee country [1] 305773 0
Australia
Date submitted for ethics approval [1] 305773 0
12/10/2020
Approval date [1] 305773 0
23/03/2021
Ethics approval number [1] 305773 0
HREC/67282/MH-2020

Summary
Brief summary
Chronic obstructive pulmonary disease (COPD) is an incurable illness characterised by airflow limitation, persisting respiratory symptoms and progressive respiratory failure..
Nasal high flow (NHF) therapy is a new respiratory support system. NHF washes out carbon dioxide from airway dead space in the lungs to improve ventilation and also generates a low-level positive airway pressure that reduces airway resistance to reduce the work of breathing.

This mixed methods research project including feasibility and qualitative studies will determine if domiciliary NHF is a feasible and acceptable intervention for severe breathlessness in COPD. Secondly these results will inform a world-first, multi-site Phase 3 RCT, to determine if long-term, domiciliary NHF is an effective and cost-effective, new intervention for severe breathlessness in people with COPD who do not qualify for domiciliary continuous oxygen therapy.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 101546 0
A/Prof Natasha Smallwood
Address 101546 0
Department of Respiratory & Sleep Medicine
The Royal Melbourne Hospital
City Campus, Level 1
Centre for Medical Research Building
Parkville Victoria 3050
Country 101546 0
Australia
Phone 101546 0
+61 3 9342 7708
Fax 101546 0
Email 101546 0
[email protected]
Contact person for public queries
Name 101547 0
A/Prof Natasha Smallwood
Address 101547 0
Department of Respiratory & Sleep Medicine
The Royal Melbourne Hospital
City Campus, Level 1
Centre for Medical Research Building
Parkville Victoria 3050
Country 101547 0
Australia
Phone 101547 0
+61 3 9342 7708
Fax 101547 0
Email 101547 0
[email protected]
Contact person for scientific queries
Name 101548 0
A/Prof Natasha Smallwood
Address 101548 0
Department of Respiratory & Sleep Medicine
The Royal Melbourne Hospital
City Campus, Level 1
Centre for Medical Research Building
Parkville Victoria 3050
Country 101548 0
Australia
Phone 101548 0
+61 3 9342 7708
Fax 101548 0
Email 101548 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
Sensitive and personal health information will be contained in individual participant data and for this reason, aggregate de-identified data only will be available.


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.