Title: A feasibility, randomised controlled trial of a complex breathlessness intervention in idiopathic pulmonary fibrosis.
Funder: Department of Health and Social Care

Abstract: Background: Idiopathic pulmonary fibrosis (IPF) is a progressive, incurable and fatal scarring lung condition with median survival of 3-5 years. Breathlessness is common and worsens as the disease progresses resulting in significant distress and functional limitation. Patients attending the Hull Pulmonary Fibrosis Support Group identified breathlessness as the symptom with greatest impact on their lives. Although two drugs have recently emerged that slow lung function decline, neither improve symptoms or quality of life. Pulmonary rehabilitation remains the only intervention that improves quality of life. However, access to programs tailored to the needs of people with pulmonary fibrosis is poor. Pulmonary rehabilitation, particularly with a large aerobic exercise component, is not suitable for or tolerated by many with IPF, especially those with advanced disease. Individually tailored pharmacological and non-pharmacological palliative care management strategies play an important role and are recommended in national guidance. However, people with IPF are underrepresented and rarely differentiated from other interstitial lung diseases in palliative breathlessness trials. The heterogeneous and unpredictable nature of IPF limits the generalisability of these findings to people with IPF. Methods: Design: We will undertake a multi-centre, fast-track (wait list), mixed-methods, randomised controlled feasibility study to inform a substantive, phase 3, randomised controlled trial of a complex breathlessness intervention in people with IPF and chronic breathlessness. Participants, Intervention and Comparator: Fifty people with IPF and chronic breathlessness despite optimal management will be recruited and randomised (1:1) to receive a complex breathlessness intervention within 1 week (fast-track group) or be placed on a waiting-list for 8 weeks prior to receiving the intervention (wait-list group). Both groups will receive all other usual care throughout the study. The intervention consists of two, one hour sessions, one week apart, with a specialist respiratory therapist. Participants will receive training in breathlessness management techniques including breathing control, hand-held fan, activity pacing, relaxation, recovery, tailored exercise and advice. A final telephone consultation with the therapist will be undertaken 1 week later. Study measures: Measures will be collected at baseline and weeks 4,8,12 and 16. Participants allocated to fast-track intervention will provide data until 16 weeks allowing longer-term follow-up in this group. Primary outcomes relate to trial feasibility (recruitment, attrition, data quality, choice of primary outcome in the definitive trial, sample size calculation). Other measures will assess the following domains: ability to cope with (0-10 numerical rating scale [NRS]) and mastery over (mastery domain from the chronic respiratory questionnaire) breathlessness; breathlessness severity (&ldquo;worst&rdquo; and &ldquo;average&rdquo; over past 24 hours 0-10 NRS); and functional capacity (shuttle walk test, Australian-modified Karnofsky Performance Scale, activity monitoring), health status (Disease specific [SGRQ-I] and generic [EQ-5D-5L]), well-being (ICECAP-SCM) and health service utilisation (recorded from hospital systems and patient reported). Analysis: Descriptive statistics will be used to describe: Recruitment: Eligibility to consent ratio, recruitment rate and participant retention rate to inform the number of sites needed to enrol sufficient participants within an acceptable timeline. Intervention: Adherence in delivery and uptake. This will provide data on acceptability and fidelity. Data quality: Amount and pattern of missing data for study measures. Outcome: Data variability across the range of outcome measures, patient experience from the qualitative interviews of study measures and the data quality (see 3) will inform the choice of primary outcome and other study measures, including health economic assessment, for the definitive trial. Health Economic Assessment: health service utilisation and health related quality of life. Stop-go rules will be applied to feasibility outcomes to assess whether a main trial is feasible.

Lay abstract: Idiopathic pulmonary fibrosis (IPF) is a scarring lung disease that affects older adults. It usually progresses over time leading to disabling shortness of breath and cough. Unfortunately, although medications can slow down the rate of lung scarring, they do not improve patients symptoms or quality of life. Shortness of breath is the most common symptom in IPF and the one which has the biggest impact on patients lives. Treatments for breathlessness have been shown to be effective for people with other lung conditions but we do not know whether they work for people with IPF. It is important that treatments are properly tested in IPF to help patients, doctors and policy makers make correct treatment decisions. When designing a study to test a treatment's effectiveness we need to understand how many patients will be suitable and willing to take part and how many complete all study tests and measurements. We also need to identify the best measurements to use and ensure that they are meaningful to patients and their carers. We will conduct a feasibility study to answer these questions. Breathless IPF patients will be randomly selected to receive the breathlessness treatment straight away or be placed on a waiting list to start the treatment 8 weeks later. The treatment will involve training patients in techniques to help their breathing. It will be delivered by a specialist therapist during 2 hour-long appointments and a telephone call over 3 weeks. Assessment of breathlessness and quality of life and measurement of daily activity will be performed at the start of the study and repeated every four weeks for a total of 16 weeks. At the end of this study, we will know if a larger study is possible, whether it is potentially cost effective and how this study should be designed.

Research activity codes: 7.1 INDIVIDUAL CARE NEEDS
Health categories: RESPIRATORY