Plain English Summary
Background and study aims
Asthma is a common condition that can cause coughing, wheezing, chest tightness and breathlessness. About 1 in 10 people with asthma have difficult to control symptoms and are described as having severe asthma. They need more healthcare support than milder disease. We know regular physical activity has important health benefits, but many patients with severe asthma avoid exercise. GPs and nurses may also be worried that exercise might worsen asthma symptoms. Physical training through short structured supervised programmes (pulmonary rehabilitation [PR]) leads to improved symptoms, quality of life and fitness in other chronic lung diseases. They are good value for money and lead to less healthcare use. However, few patients with severe asthma have access to such programmes. Our local PR service has accepted these patients, but patients said they would prefer to attend a specific programme for asthma. The aim of this study is to find out whether people with severe asthma would benefit from a PR programme specifically for asthma.
Who can participate?
Patients with severe asthma.
What does the study involve?
Participants are randomly allocated to one of two groups. One group attends a PR programme specifically for asthma. The other group receives usual care (disease education and exercise advice from asthma nurses).
What are the possible benefits and risks of participating?
Not provided at time of registration
Where is the study run from?
Glenfield Hospital (UK)
When is the study starting and how long is it expected to run for?
December 2013 to November 2016
Who is funding the study?
National Institute for Health Research (NIHR) (UK)
Who is the main contact?
Dr Rachael Evans
Trial website
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
CLRN 127552
Study information
Scientific title
A feasibility study to inform the development of a multicentre randomised controlled trial of an asthma-tailored pulmonary rehabilitation programme versus usual care for individuals with severe asthma
Acronym
Study hypothesis
Patients with severe asthma have a high morbidity and healthcare cost despite currently available therapies. Activity limitation is common, leading to reduced health-related quality of life (HRQoL). Cardiorespiratory fitness (CRF) is a strong predictor of mortality and asthma has a strong inverse association with CRF. Despite this, patients with severe asthma are often excluded from exercise schemes due to perceived higher risks. Pulmonary rehabilitation (PR), with core components of exercise training and multi-professional education, is an integral part of the management of patients with chronic lung disease, with grade A evidence for improvements in dyspnoea, exercise tolerance and HRQoL. International guidance suggests inclusion of patients with asthma, but there is little published evidence evaluating either existing or tailored regimens in severe asthma, leading to few patients being referred. Our patients stated a preference for a PR programme specifically for their disease. We propose a feasibility study to inform the study design of a large multicentre randomised controlled trial (RCT) of asthma-tailored PR (AT-PR) for individuals with severe asthma compared to usual care (UC).
The aims of the proposed study are, in patients with severe asthma, to:
1. Understand the facilitators and barriers to regular physical activity and exercise
2. Understand healthcare professionals attitudes to exercise for this group
3. Perform a small scale version of the eventual RCT to:
3.1. Provide information on recruitment rate, retention rate, adverse events, accessibility and acceptability of the AT-PR programme, to assess the feasibility of the proposed study protocol, and to design and pilot a suitable patient cost questionnaire to be used in the proposed cost-effectiveness economic evaluation in the subsequent RCT
3.2. Identify further barriers or facilitators to participation in a AT-PR programme
4. To facilitate patient involvement in the design, conduct and dissemination for the multicentre trial.
Ethics approval
NRES Committee East Midlands - Leicester, 17/10/2013, ref: 13/EM/0323
Study design
Qualitative study and small scale feasibility study of a randomised controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Other
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details to request a patient information sheet
Condition
Severe asthma
Intervention
This feasibility project uses the Medical Research Council (MRC) guidelines on developing a complex intervention. It will have four stages and adopts a mixed methods approach. Recruitment for each stage will be separate.
The project will be conducted as stages:
1. A qualitative study involving semi-structured interviews will explore attitudes to exercise
2. A qualitative study involving focus groups of healthcare professionals will explore attitudes to exercise for severe asthma
3. A small scale feasibility study of an RCT of AT-PR versus UC will be performed. A qualitative approach will be used to explore the facilitators and barriers to participation in a AT-PR and the study protocol. AT-PR, modelled on our local successful PR programme for chronic obstructive pulmonary disease (COPD), will be exclusively for severe asthma and further modified according to the findings from stage 1 and 2. Usual care (DAC) will include disease education and exercise advice from asthma nurses. We plan to randomise 40 patients to the intervention arm and 20 patients to usual care. We estimate conservatively that we will recruit 30% of those invited to estimate the recruitment rate with a precision of at least +/- 7%. We suggest a conservative dropout rate of 25% (our local PR dropout rate is approximately 15%); recruiting 40 patients to the AT-PR programme, the precision of the estimated retention rate would be at least +/- 14%. From experience to date, we are expecting very few serious adverse events relating to the exercise programme. Based on a rate of 2.5%, the rate would be estimated to be less than 13%. All precisions are based on two-sided 95% confidence intervals.
4. The patient involvement during the project will be assessed to make any necessary adaptations for the multicentre trial
Intervention type
Behavioural
Phase
Drug names
Primary outcome measure
To establish the practicality of a definitive multicentre RCT, the primary outcomes for the feasibility study are:
1. Recruitment rate
2. Retention rate
3. Incidence of adverse events
Secondary outcome measures
The outcome measures proposed for the multicentre trial will be included to assess patient acceptability of the tests, study protocol and data completion. The outcome measures to assess the intervention will be collected at baseline, 12 weeks and 6 months by a blinded investigator. We have experience in using all proposed outcome measures. Baseline demographics will be recorded including body mass index and spirometry.
Safety
1. Any adverse events directly or indirectly related to the exercise measurements and training sessions will be recorded. Any severe adverse event will be reported to our Research and Development office immediately. An external respiratory physician has agreed to independently assess any adverse events and stop the trial if necessary.
2. A full cardiopulmonary exercise test with expiratory gas analysis will be performed on a treadmill. Exercise-induced bronchoconstriction will be assessed by a flow-volume loop, before and after the treadmill test, before and after 12 weeks. All patients will be included in the programme and excluded only if they have an adverse event. This data will used as an outcome measure not just for safety.
3. Asthma control and disease activity will be assessed by:
3.1. The Juniper Asthma Control Score
3.2. Measuring airway inflammation by induced sputum count before and after the intervention
3.3. By comparing the preceeding 9 months unscheduled healthcare visits for asthma with 9 months after and including the intervention, including GP, accident and emergency attendance and hospital admissions.
Cost effectiveness
The Euroqol (EQ-5D) questionnaire will be used to assess quality-adjusted life-years (QALYs) at baseline, 12 weeks and 6 months. Costs will be calculated using NHS tariffs. All treatment including medication, adverse events and any over the counter medication will be recorded. Cost effectiveness will be assessed with the help of a health economist using methodology previously described.
The usual outcome measures for PR will be assessed to ensure acceptability of the protocol for the multicentre trial. As exercise rehabilitation is a complex medical intervention there are a number of different outcomes to assess including:
1. Asthma-specific health-related quality of life (HRQoL) using the asthma quality of life questionnaire (AQLQ) and Chronic Respiratory Questionnaire
2. Hospital Anxiety and Depression Scale
3. Incremental treatmill test (ITM)
4. Incremental shuttle walking test (ISWT)
5. Endurance shuttle walk test (ESWT)
6. Compliance with the supervised and home training programme
Acceptability and feasibility of other outcome measures that may be used for the multicentre RCT:
1. Domestic physical activity measured by tri-axial accelerometers (Sensewear pro 3). This is a valid measurement of daily activity to assess behaviour change
2. Quadriceps strength assessed by an adapted chair with a strain gauge
3. Venous blood sampling
4. Dual-energy X-ray absorptiometry (DEXA) scanning
Exacerbations of asthma
Patients will be asked to keep a diary of their exacerbations, treatment and unscheduled healthcare visits. Participants in both groups, along with their GPs, will receive a personalised management plan with guidance about initiating steroids for exacerbations. If participants present to the investigating team they will be reviewed by an independent clinician with the decision to commence treatment with oral prednisolone based on standard clinical guidelines. The patients will be asked to stop coming to the AT-PR sessions for any exacerbation requiring steroid treatment. If they are not recovered enough to start participation within 2 weeks they will be classified as a dropout. Similarly they will be excluded from the UC limb if they are not back to normal within 2 weeks to avoid bias.
Overall trial start date
18/12/2013
Overall trial end date
10/09/2017
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
Patients with severe asthma (defined as asthma which remains symptomatic at steps 4-5 of the British Thoracic Society asthma guidelines), despite management for >6 months in the Glenfield Difficult Asthma Clinic (DAC), will be recruited. All patients will have a thorough diagnostic work up and a treatment strategy targeting eosinophillic airway inflammation to optimise control; exercise-induced asthma is often a reflection of poor control.
Participant type
Patient
Age group
Not Specified
Gender
Not Specified
Target number of participants
Stage 1: 2-30 patients; Stage 2: 6-8 focus groups of 6-10 healthcare professionals; Stage 3: 60 patients; Stage 4: patient representatives and the steering group commitee
Participant exclusion criteria
1. Severe exacerbation within a month of entry
2. Inability to exercise e.g. due to significant musculoskeletal or neurological abnormalities
Recruitment start date
18/12/2013
Recruitment end date
02/01/2017
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Glenfield Hospital
Leicester
LE3 9QP
United Kingdom
Sponsor information
Organisation
University Hospitals of Leicester NHS Trust (UK)
Sponsor details
c/o Mrs Carolyn Maloney
Research & Development Manager
Leicester
LE5 4PW
United Kingdom
Sponsor type
University/education
Website
Funders
Funder type
Government
Funder name
National Institute for Health Research, Research for Patient Benefit Grant, PB-PG-0712-28063
Alternative name(s)
NIHR
Funding Body Type
government organisation
Funding Body Subtype
Federal/National Government
Location
United Kingdom
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list
2016 protocol in: http://www.ncbi.nlm.nih.gov/pubmed/27009149