Title: Ambulatory oxygen for pulmonary fibrosis (OxyPuF)
Funder: Department of Health and Social Care

Abstract: Idiopathic pulmonary fibrosis (IPF) is a devastating condition of unknown cause that results in progressive, irreversible scarring of the lung (pulmonary fibrosis). IPF has, until recently, been considered to be a rare disease however is thought to be responsible for as many as 1 in 100 deaths in the UK, killing 5,300 people a year (more than cancers such as those of the stomach, liver and skin). Initially sufferers notice shortness of breath and a persistent dry cough which can be embarrassing as well as impacting on sleep and quality of life. As a result of this symptom reduced physical activity occurs, which may affect basic tasks such as washing, dressing and eating. Loss of appetite, weight loss, fatigue, anxiety and depression add to the already high symptom burden. Treatment may include exercise (pulmonary rehabilitation), and tablets designed to reduce processes in the lung which lead to scarring (anti-fibrotics). Even with the best available treatments half of patients survive only 3 years from the time of diagnosis – a prognosis similar to lung cancer_x000D_ Increasing breathlessness can happen as a result of low oxygen levels, especially when trying to be active, although can occur even in the context of normal oxygen levels. In other respiratory conditions, such as chronic obstructive pulmonary disease, oxygen is used to help relieve symptoms and extend life in selected patients. However, there has been very little research into the management of low oxygen levels in IPF and no evidence as to whether oxygen is beneficial if used just when walking (ambulatory oxygen). We plan to assess the benefit, if any, of ambulatory oxygen in the management of people with IPF by conducting a randomised controlled trial in 260 IPF patients who are breathless on walking. We will assess the impact on quality of life, breathlessness and ability to exercise is any better in patients who receive ambulatory oxygen compared to those receiving best supportive care. We will also interview patients and clinicians to assess how acceptable oxygen treatment of this kind is, and will determine if the treatment is cost-effective. If we are able to demonstrate benefit, guidelines in the UK are likely to be updated to include oxygen therapy as a routine treatment. Conversely, if it’s not found to be helpful, it would help drive earlier focus on rehabilitation to maintain functional capacity and independence._x000D_ Our team comprises academic respiratory consultants who specialise in IPF, a respiratory academic who has conducted a previous trial using ambulatory oxygen, a statistician, a health economist and a medical sociologist, as well as support from a clinical trials unit. We also have a patient co-applicant and close links to a charity, Action Pulmonary Fibrosis. Patients will be represented within regular trial management meetings, on our trial steering committee, and will act as co-researchers with us in some parts of the study. We will also be using arts based approaches to communicate our results outside academic audiences. The trial will take approximately 3 years to complete.

Lay abstract: Research question: What is the clinical and cost-effectiveness of ambulatory oxygen therapy (AOT) in patients with idiopathic pulmonary fibrosis (IPF)?_x000D_ Background_x000D_ Idiopathic pulmonary fibrosis (IPF) is a devastating condition of unknown cause that results in progressive, irreversible scarring of the lung, manifesting as breathlessness and dry cough. IPF has, until recently, been considered to be a rare disease however is thought to be responsible for as many as 1 in 100 deaths in the UK, killing 5,300 people a year. Ambulatory oxygen is commonly used in IPF to relieve exertional breathlessness, although evidence to support this strategy is lacking. This pragmatic RCT will test whether use of AOT is beneficial in people with IPF who are breathless on exertion._x000D_ Objectives_x000D_ 1. Determine whether HRQoL described by the K-BILD (validated questionnaire in IPF) is superior after AOT compared to best supportive care at 6 months after commencement of therapy_x000D_ 2. Determine whether breathlessness, determined by the MRC score, is superior after AOT compared to best supportive care at 6 months, as above_x000D_ 3. Determine whether exercise capacity and physical activity, as described by the six minute walk test (6MWT), and a self reported activity questionnaire (IPAQ) respectively, is superior after AOT compared to best supportive care at 6 months, as above_x000D_ 4. Assess cost effectiveness of AOT_x000D_ 5. Assess the acceptability of AOT_x000D_ _x000D_ Methods_x000D_ This is a pragmatic, randomized, controlled trial in 260 patients with IPF who are breathless on exertion and do not meet criteria for long term oxygen therapy, randomizing in a 1:1 ratio between AOT and best supportive care. Primary outcome is a quality of life questionnaire validated in pulmonary fibrosis, the K-BILD, measured at 6 months. We have calculated our sample size based on the minimum clinically important difference in K-BILD; assuming power of 90% and 5% 2-sided significance level, we need to recruit 130 per arm, after accounting for 20% dropout. The trials unit’s web based randomization algorithm minimizes on factors potentially influencing response to AOT such as severity of IPF, desaturation to <88% present on walking, current or recent (within 6 months) pulmonary rehabilitation, and recruitment centre. Secondary outcomes include symptoms, exercise capacity and cost-effectiveness. A process evaluation will include assessment of trial fidelity and acceptability of the intervention. The latter will be assessed using qualitative research methods and visual arts approaches with patients and staff (n~60), incorporating co-analysis by patients._x000D_ Timelines for delivery_x000D_ 3 years, comprising 6 month set-up period, 18 months enrolment, 6 months follow up and 6 months to analyse data. Internal pilot will assess recruitment, withdrawal and crossover rates._x000D_ Anticipated impact and dissemination_x000D_ Dissemination will occur through conferences and publications, as well as through our PPI group, Action Pulmonary Fibrosis, the ILD nursing network, arts based approaches and a newsletter. Impact is anticipated through updates to UK NICE guidance around AOT use in IPF.

Research activity codes: 6.7 PHYSICAL
Health categories: RESPIRATORY