Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12620000283976
Ethics application status
Approved
Date submitted
28/01/2020
Date registered
3/03/2020
Date last updated
3/03/2020
Date data sharing statement initially provided
3/03/2020
Type of registration
Retrospectively registered

Titles & IDs
Public title
Understanding Breathlessness in Asthma
Scientific title
Understanding Breathlessness in Asthma
Secondary ID [1] 299909 0
Nil known
Universal Trial Number (UTN)
Trial acronym
UBA
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Severe asthma 315331 0
Mild to moderate asthma 315332 0
Condition category
Condition code
Respiratory 313634 313634 0 0
Asthma

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
A cross-sectional observational study will be conducted in stable severe and non-severe asthma participants.

Participants will consent to-
1) Completing the tests involved in the study
2) Completing questionnaires to obtain research data
3) A copy of their results being sent to their General Practitioner
4) Allowing research personnel access to their medical record and to record attendance and lung function results in their file.

All participants will undergo a multidimensional assessment of breathlessness over 2 visits 2-4 weeks apart that will take no longer than 2.5 hours per visit.

The multidimensional assessment involves the participant undergoing measures of blood pressure, height and weight, pulmonary function testing, saline challenge, six minute walk test, blood collection, physical activity monitoring, respiratory inductive plethysmography (RIP), fractional exhaled nitric oxide (FeNO), capnography, breath hold time, bioimpedence analysis and a laryngoscopy.

The participant will also complete some questionnaires to gain information about general health or quality of life, medical history and medications, asthma symptoms, overall well-being and mental health, activity levels and problems related to breathlessness.

A subset of participants who complete the multidimensional assessment and are identified as having vocal cord dysfunction (VCD) will be invited to participate in a 2-hour qualitative interview on a later day. Participants with VCD or breathlessness from other causes will also be invited to participate in a 3-hour qualitative art activity on later day.
Intervention code [1] 316181 0
Diagnosis / Prognosis
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 322072 0
The proportion of people with breathlessness defined by an mMRC score greater than or equal to 2
Timepoint [1] 322072 0
baseline
Secondary outcome [1] 377228 0
Nil
Timepoint [1] 377228 0
Not applicable

Eligibility
Key inclusion criteria
All Participants
-18 years of age or older.
-Confirmed diagnosis of asthma
-Evidence of variable airflow limitation within the last 10 years:
*Bronchodilator response (BDR) greater than or equal to 200ml OR greater than or equal to 12% (post-bronchodilator FEV1 following administration of 400µg salbutamol).
*Airway hyper-responsiveness (AHR) in response to any standard challenge agent.
or
*Peak flow variability (diurnal; variation greater than or equal to 15% or greater than or equal to 50ml).

Severe Asthma Participants
Severe asthma is defined as asthma requiring high-dose inhaled corticosteroids with a second controller to prevent “uncontrolled” disease or disease that remains “uncontrolled” despite therapy.
To meet the criteria for severe asthma, participants will additionally require the following to be met:
1. Prescribed high-dose inhaled corticosteroids (>1000µg beclomethasone equivalent) PLUS a second controller (may include long-acting beta agonists; and/or long-acting muscarinic antagonists, and/or maintenance oral corticosteroids greater than or equal to 50% of the past year; and/or montelukast; and/or theophylline).
or
Requires a monoclonal antibody (mAb) therapy to control asthma or remains uncontrolled despite a mAb.
2. Have uncontrolled asthma determined by:
a. scores on the Asthma Control Questionnaire greater than or equal to 1.5;
b. and/or frequent severe exacerbations (greater than or equal to 2 systemic corticosteroids of 3 or more days each in the previous year);
c. and/or a serious exacerbation in the previous year (hospitalisation, intensive care unit stay, mechanical ventilation);
d. and/or persistent airflow limitation (pre-bronchodilator FEV1 <80% predicted in the face of a reduced FEV1/FVC <0.7).

Inclusion for qualitative studies

Qualitative Interview: Participants with asthma who have co-existing VCD defined either a fall in FIF of greater than or equal to 25% or demonstrated paradoxical vocal fold movement on laryngoscopy.

Art Based Study: Two groups will be recruited. 1) Those with severe asthma and breathlessness but not VCD. That is a score of greater than or equal to 2 on the Modified Medical Research Council Dyspnea Scale [31] and either a fall in FIF of <25% or no demonstrated paradoxical vocal fold movement during laryngoscopy. 2) Those with severe asthma, breathlessness and VCD. That is a score of greater than or equal to 2 on the Modified Medical Research Council Dyspnea Scale and either a fall in FIF of greater than or equal to 25% or demonstrated paradoxical vocal fold movement on laryngoscopy.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Pregnant.
2. High dependence on medical care, including recent intensive care unit admission.
3. Significant life-limiting comorbidity.
4. Current lung cancer or other blood, lymphatic or solid organ malignancy.
5. Primary diagnosis of a lung disease other than asthma.
6. Cognitive impairment, poor English language skills or significant untreated hearing impairment that prevents completion of data collection forms or understanding verbal instructions.
7. Inability to attend study visits.
8. Exacerbation (use of oral corticosteroids or an increase from maintenance dose of oral corticosteroids for greater than or equal to 3 days) in the previous four weeks. These participants will have their visit postponed.

Study design
Purpose
Natural history
Duration
Cross-sectional
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
Sample Size

Cross-sectional study
To detect a difference between groups of 0.5 standard deviation units (medium effect size) at 85% power and a = 0.05, we require 118 patients (59 severe asthma, 59 mild-moderate asthma). To conduct cluster analysis, we require 2m participants (m=number of predictors). Therefore, with 7 predictors, we require 128 participants. Allowing for a 10% attrition rate between assessments, we aim to recruit 140 participants in total.

Qualitative studies
Qualitative interviews with VCD patients. A sample size of n=25 will be considered adequate. If data saturation has not been achieved we will seek a variation to increase the sample.

Art-based assessment of patient experience
We will recruit 30 participants, 15 with VCD and 15 without. The sample size was guided by Cheung et al who reported 18 participants in the first published study investigating adult’s perspectives of asthma using drawings.

Statistical Methods

Quantitative Data: Continuous and categorical indicators of breathlessness will be compared between severe and mild-moderate asthma via appropriate inferential statistics (independent samples t-test, Mann–Whitney U test, chi-square, Fisher’s exact test). Associations between indicators of breathlessness and clinical characteristics will be analysed using linear, logistic and negative binomial regression, as appropriate. Unsupervised cluster analysis will be conducted to identify distinct groups of patients based on the correlates of breathlessness.

Qualitative Interviews: Recordings will be transcribed verbatim and transcripts will be anonymised and entered into NVivo to assist data management and coding. Comparison, charting and mapping will occur for cross-case examination that will assist in interpretation. Dependability and confirmability to ensure the trustworthy of this research will be undertaken via audit trail with records of the research path being kept during the study.

Art based Qualitative Study: As drawings can be abstract and interpreted subjectively in various ways, the analyses will be grounded in the participants’ own accounts of their images. Participants’ descriptions of their drawings will be transcribed verbatim. Sections of text will be examined alongside the relevant image, and a coding approach will be used to cluster thematic material.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
6/01/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
140
Accrual to date
8
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 15306 0
John Hunter Hospital - New Lambton
Recruitment postcode(s) [1] 28617 0
2305 - New Lambton

Funding & Sponsors
Funding source category [1] 304367 0
University
Name [1] 304367 0
University of Newcastle
Country [1] 304367 0
Australia
Primary sponsor type
University
Name
University of Newcastle
Address
University Drive
Callaghan NSW 2308
Country
Australia
Secondary sponsor category [1] 304616 0
None
Name [1] 304616 0
Address [1] 304616 0
Country [1] 304616 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 304811 0
Hunter New England Human Research Ethics Committee
Ethics committee address [1] 304811 0
Ethics committee country [1] 304811 0
Australia
Date submitted for ethics approval [1] 304811 0
31/07/2019
Approval date [1] 304811 0
13/09/2019
Ethics approval number [1] 304811 0
2019/ETH12515

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

Contacts
Principal investigator
Name 98282 0
Prof Vanessa McDonald
Address 98282 0
Level 2, Hunter Medical Research Institute
1 Kookaburra Circuit, New Lambton Heights NSW 2305
Country 98282 0
Australia
Phone 98282 0
+61 2 4042 0146
Fax 98282 0
+61 2 4042 0046
Email 98282 0
[email protected]
Contact person for public queries
Name 98283 0
Amber Smith
Address 98283 0
Level 2, Hunter Medical Research Institute
1 Kookaburra Circuit, New Lambton Heights NSW 2305
Country 98283 0
Australia
Phone 98283 0
+61 2 4042 0134
Fax 98283 0
+61 2 4042 0046
Email 98283 0
[email protected]
Contact person for scientific queries
Name 98284 0
Vanessa McDonald
Address 98284 0
Level 2, Hunter Medical Research Institute
1 Kookaburra Circuit, New Lambton Heights NSW 2305
Country 98284 0
Australia
Phone 98284 0
+61 2 4042 0146
Fax 98284 0
+61 2 4042 0046
Email 98284 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?
Anonymised demographic and primary and secondary outcome data underlying published results
When will data be available (start and end dates)?
following publication -no end date
Available to whom?
Case by case basis at the discretion of the primary sponsor
Available for what types of analyses?
Individual patient data meta-analysis
How or where can data be obtained?
Access subject to approvals by Principal Investigator
Professor Vanessa McDonald 02 40420146


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
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