Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621000855820
Ethics application status
Approved
Date submitted
24/05/2021
Date registered
2/07/2021
Date last updated
6/12/2022
Date data sharing statement initially provided
2/07/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Immediate effects of the MetaNeb® compared to huff and cough in adults with stable cystic fibrosis.
Scientific title
Immediate effects of the MetaNeb® on regional lung perfusion, ventilation and other measures of lung function compared to those of huff and cough in adults with stable cystic fibrosis.
Secondary ID [1] 304300 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cystic Fibrosis
 322033 0
Condition category
Condition code
Human Genetics and Inherited Disorders 319764 319764 0 0
Cystic fibrosis
Respiratory 319765 319765 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The MetaNeb® System (Hill-Rom, Inc. Batesville, Indiana, USA) is a relatively new device that has been developed to facilitate airway clearance in individuals with acute and chronic
lung conditions, including cystic fibrosis (CF). It was introduced for clinical use in Australia in 2016. The MetaNeb® incorporates two modes; (i) continuous positive expiratory pressure (CPEP) and, (ii) continuous high frequency oscillation (CHFO). The CPEP mode assists with lung expansion and recruitment by delivering PEP, whereas the CHFO mode aids secretion clearance by providing pulsatile positive airway pressure at two different frequencies (similar to intrapulmonary percussive ventilation [IPV].)These modes deliver positive airway pressure and airway oscillation throughout both inspiration and expiration. The device also allows three varying levels of PEP to be applied at the mouthpiece, and a nebulised mucolytic (e.g. saline or hypertonic saline) to be delivered while the device is in use. Multiple interfaces can be used to deliver the therapy including a face mask, mouthpiece or tracheostomy. In this study we will be using the mouthpiece only.

For the experimental intervention undertaken during visit 1, participants will be asked to complete 30 minutes of supervised physiotherapy in sitting, using the MetaNeb® system (Hill-Rom, Inc. Batesville, Indiana, USA) with their usual inhaled mucolytics (either normal or hypertonic saline). The 30 minute MetaNeb treatment session will comprise breathing in and out of the mouthpiece for 5x 5 minute cycles of MetaNeb® therapy (2.5 mins each of CPEP and CHFO modes) interspersed with 1 minute of sputum clearance using huff and/or cough. This treatment will be used on the first study visit only. Each participant will have the settings of the MetaNeb® titrated to optimise comfort and these settings will be recorded. All treatment sessions will occur in the Radiology department at Sir Charles Gairdner Hospital (SCGH) and will be conducted by either the PhD candidate or another trained member of the SCGH CF Physiotherapy team. Across both study visits, the 30-minute intervention period and 30-minute rest period will be video recorded (camera will be placed behind the participant and will not capture their face). This video recording will be used to: (i) count the number of number of huff and coughs performed during visit 1 and standardise this variable at visit 2 and (ii) provide the gold standard (criterion measure) of the number of coughs and huffs taken to establish agreement with the Spire Health Tag. Each visit will be separated by at least 48 hours and be within a two-week period (washout period). During the washout period participants will be asked to maintain their usual medications, airway clearance techniques and exercise habits.

When first designing the study, our team did consider randomisation. However, this is not possible. This is because, in order to determine the true effect of the MetaNeb®, we need to use an experimental design in which the only difference between the two sessions is the use of the MetaNeb®. Every other factor that can influence airway clearance, such as the number of huffs and coughs the participant does, must be standardised between sessions. During the treatment session with the MetaNeb®, the participant will huff and cough. They will do this on request (by the treating physiotherapist), but this will also occur spontaneously. We have no control over spontaneous huffing and coughing during the MetaNeb® session (this is a reflex response to the changes in pressure and flow within the airways). Based on our clinical experience doing ACT with these patients, in some people, the MetaNeb® is likely to induce a lot of spontaneous huffing and coughing, and in other people, will not induce any. We will not know how the participant will respond until we perform the MetaNeb® session. For this reason, we must perform the MetaNeb® session first, so we can count the number of ‘requested’ and ‘spontaneous’ huffs and coughs so this can be standardised at the next session. This methodological consideration is well accepted in the literature, and has been described in earlier work (Dwyer et al 2019)
Intervention code [1] 320643 0
Treatment: Devices
Comparator / control treatment
For the control intervention undertaken during visit 2, participants will be asked to complete a 30-minute session, in sitting, with their usual inhaled mucolytic (either normal or hypertonic saline). During this session, they will be directed to cough and huff, the same number of times that they did for visit 1 (MetaNeb Intervention). All treatment sessions will occur in the Radiology department at Sir Charles Gairdner Hospital (SCGH) and will be conducted by either the PhD candidate or another trained member of the SCGH Cystic Fibrosis (CF) Physiotherapy team. As per the intervention session, the 30-minute control intervention period and 30-minute rest period will be video recorded (camera will be placed behind the participant and will not capture their face). This video recording will be used to: (i) count the number of number of huff and coughs performed during visit 1 and standardise this variable at visit 2 and (ii) provide the gold standard (criterion measure) of the number of coughs and huffs taken to establish agreement with the Spire Health Tag.
Control group
Active

Outcomes
Primary outcome [1] 327624 0
Lung structure assessed using a standard T2 Magnetic Resonance Imaging (MRI) sequence (SPACE)
Timepoint [1] 327624 0
Prior to and thirty minutes after each treatment session
Primary outcome [2] 327990 0
Lung structure assessed using a novel T1 MRI sequence (SpiralVIBE)
Timepoint [2] 327990 0
Prior to and thirty minutes after each treatment session
Primary outcome [3] 327991 0
Regional lung perfusion and ventilation measured using a Fourier decomposition MRI sequence (TRUFI)
Timepoint [3] 327991 0
Prior to and thirty minutes after each treatment session
Secondary outcome [1] 395970 0
Impedance of the respiratory system (Zrs) and its two components (respiratory reactance [Xrs] and resistance [Rrs]) using forced oscillation technique
Timepoint [1] 395970 0
Prior to and thirty minutes after each treatment session
Secondary outcome [2] 395971 0
Forced expiratory volume in one second (FEV1) via spirometry
Timepoint [2] 395971 0
Prior to and thirty minutes after each treatment session
Secondary outcome [3] 395972 0
Sputum expectorated using digital scale to measure sputum wet weight
Timepoint [3] 395972 0
Prior to and thirty minutes after each treatment session
Secondary outcome [4] 395973 0
Sputum expectorated using digital scale to measure sputum dry weight
Timepoint [4] 395973 0
Prior to and thirty minutes after each treatment session
Secondary outcome [5] 395974 0
Symptoms commonly reported by individuals with CF such as fatigue, dyspnoea, chest pain, nausea, dizziness, ease of sputum expectoration and sense of chest congestion using a modified Edmonton Symptom Assessment Scale revised.
Timepoint [5] 395974 0
Prior to and thirty minutes after each treatment session
Secondary outcome [6] 395975 0
Patient acceptability of the MetaNeb® using a 10cm visual analogue scale (VAS) to rate their overall experience of using the device
Timepoint [6] 395975 0
Prior to and thirty minutes after each treatment session
Secondary outcome [7] 395976 0
Mean airway pressure including peak inspiratory and expiratory pressure (at the mouth) generated by each participant whilst using the MetaNeb®, using an electronic strip chart recording system with an in-line calibrated pneumotach
Timepoint [7] 395976 0
During the first 5 minutes of the MetaNeb treatment session
Secondary outcome [8] 395977 0
Number of coughs using a video recorder
Timepoint [8] 395977 0
During treatment session and 30-minute rest period following treatment
Secondary outcome [9] 395978 0
Number of coughs using the Spire Health Tag
Timepoint [9] 395978 0
During treatment session and 30-minute rest period following treatment
Secondary outcome [10] 395979 0
Forced vital capacity (FVC) via spirometry
Timepoint [10] 395979 0
Prior to and thirty minutes after each treatment session
Secondary outcome [11] 397170 0
Mean flow including peak inspiratory and expiratory flow (at the mouth) generated by each participant whilst using the MetaNeb®, using an electronic strip chart recording system with an in-line calibrated pneumotach
Timepoint [11] 397170 0
During the first 5 minutes of the MetaNeb treatment session
Secondary outcome [12] 397171 0
Mean tidal volume (at the mouth) generated by each participant whilst using the MetaNeb®, using an electronic strip chart recording system with an in-line calibrated pneumotach
Timepoint [12] 397171 0
During the first 5 minutes of the MetaNeb treatment session
Secondary outcome [13] 397172 0
Number of huffs using a video recorder
Timepoint [13] 397172 0
During treatment session and 30-minute rest period following treatment
Secondary outcome [14] 397173 0
Number of huffs using the Spire Health Tag
Timepoint [14] 397173 0
During treatment session and 30-minute rest period following treatment
Secondary outcome [15] 397174 0
Agreement of the number of coughs between the Spire Health Tag and the gold standard - video recording
Timepoint [15] 397174 0
During treatment session and 30-minute rest period following treatment
Secondary outcome [16] 397175 0
Agreement of the number of huffs between the Spire Health Tag and the gold standard - video recording
Timepoint [16] 397175 0
During treatment session and 30-minute rest period following treatment

Eligibility
Key inclusion criteria
Inclusion criteria will comprise individuals with CF who: (i) are aged greater than or equal to 18 years, (ii) are currently managed by the adult CF service at SCGH and (iii) produce 30mL or more of sputum per 24 hours.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria will comprise: (i) a current or recent (within the last 4 weeks) acute exacerbation of CF, (ii) current pregnancy, (iii) current fresh haemoptysis (if a participant has blood stained sputum but not fresh blood, advice will be sought from medical team about suitability for the study), (iv) current or previous pneumothorax within last 12 months, (v) the inability to provide written informed consent and (vi) anyone who answers yes to any of the questions in our COVID-19 screening questionnaire which has been adapted for the CF population from the Sir Charles Gairdner Osborne Park Health Care Group (SCGOPHCG) patient screening questions: COVID-19 Nov 2020. Participants with implantable medical devices will be screened to determine if their device is compatible with fMRI prior to recruitment into the study.

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)
Allocation is not concealed
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



The people analysing the results/data
Intervention assignment
Crossover
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
There are little published data to guide sample size calculations for this study. However, earlier work in children with CF has demonstrated a reduction (improvement) in the global score obtained using fMRI (which represents changes in morphology and perfusion) following one month of antibiotic therapy from 18±2 to 12±3 (p<0.05) (Wielputz et al 2014). To detect a change in global score equal to 3 (i.e. half the magnitude, which is >10% from baseline and is likely to be meaningful), assuming a larger standard deviation in our adult sample of 4.5 (a = 0.05, 1-ß = 0.8), we need paired data on 20 participants. Therefore, we will keep recruiting until we have completed paired data on 20 participants.

Stata software (Version 16.0, StataCorp LLC, College Station, TX, USA) will be used for data analysis. Descriptive summaries of patient characteristics and measures of pressure, flow and volume generated using the MetaNeb® will consist of means and standard deviations (SD) or medians and interquartile ranges (IQR) for continuous data and frequency distributions for categorical data. The distribution of data will be checked using frequency histograms and the Shapiro-Wilk test. Associations between changes in lung structure, regional perfusion and ventilation, respiratory mechanics and airflow obstruction (from fMRI, FOT, and spirometry) pre- and post-intervention will be examined using generalised linear mixed models (GLMM) with random effects for slope and intercept, adjusting for disease severity. Participants unable to complete the full assessment and treatment periods will still be included in the analysable dataset as GLMM uses all available observed data to compute maximum likelihood estimates. Agreement between observed coughs/huffs (direct observation) and recorded coughs/huffs (The Spire Health Tag) will be examined using a Bland Altman Plot. A p value of >0.05 will be considered statistically significant. Participant data will be analysed using the intention to treat principle.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
15/07/2021
Actual
7/11/2021
Date of last participant enrolment
Anticipated
1/01/2023
Actual
Date of last data collection
Anticipated
1/01/2023
Actual
Sample size
Target
20
Accrual to date
8
Final
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 19524 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment postcode(s) [1] 34133 0
6009 - Nedlands

Funding & Sponsors
Funding source category [1] 308676 0
Charities/Societies/Foundations
Name [1] 308676 0
Institute for Respiratory Health
Country [1] 308676 0
Australia
Primary sponsor type
University
Name
Curtin University
Address
Kent St, Bentley WA 6102
Country
Australia
Secondary sponsor category [1] 309553 0
None
Name [1] 309553 0
Address [1] 309553 0
Country [1] 309553 0
Other collaborator category [1] 281802 0
Hospital
Name [1] 281802 0
Sir Charles Gairdner Hospital
Address [1] 281802 0
Hospital Ave, Nedlands WA 6009
Country [1] 281802 0
Australia
Other collaborator category [2] 281803 0
Charities/Societies/Foundations
Name [2] 281803 0
Telethon Kids Institute
Address [2] 281803 0
Northern Entrance, Perth Children's Hospital, 15 Hospital Ave, Nedlands WA 6009
Country [2] 281803 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 308598 0
Sir Charles Gairdner and Osborne Park Health Care Group Human Research Ethics Committee
Ethics committee address [1] 308598 0
Ethics committee country [1] 308598 0
Australia
Date submitted for ethics approval [1] 308598 0
30/09/2020
Approval date [1] 308598 0
29/03/2021
Ethics approval number [1] 308598 0
RGS0000003484
Ethics committee name [2] 308600 0
Curtin University
Ethics committee address [2] 308600 0
Ethics committee country [2] 308600 0
Australia
Date submitted for ethics approval [2] 308600 0
16/04/2021
Approval date [2] 308600 0
03/06/2021
Ethics approval number [2] 308600 0
HRE2021-0316

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

Contacts
Principal investigator
Name 111278 0
Miss Naomi Chapman
Address 111278 0
Physiotherapy Department, Ground Floor A block
Sir Charles Gairdner Hospital
Verdun Street
Nedlands WA 6009
Country 111278 0
Australia
Phone 111278 0
+61 08 6457 2337
Fax 111278 0
Email 111278 0
[email protected]
Contact person for public queries
Name 111279 0
Naomi Chapman
Address 111279 0
Physiotherapy Department, Ground Floor A block
Sir Charles Gairdner Hospital
Verdun Street
Nedlands WA 6009
Country 111279 0
Australia
Phone 111279 0
+61 08 6457 2337
Fax 111279 0
Email 111279 0
[email protected]
Contact person for scientific queries
Name 111280 0
Kylie Hill
Address 111280 0
Curtin School of Allied Health
Curtin University
Kent Street
Bentley WA 6102
Country 111280 0
Australia
Phone 111280 0
+61 08 9266 2774
Fax 111280 0
Email 111280 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


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.