A multi-centre double-blind randomised placebo-controlled group-sequential superiority trial to assess the effectiveness and cost-effectiveness of oral Corticosteroids in patients witH fibrOtic hypeRsensitivity pneUmonitiS (CHORUS).

Research question: What is the effectiveness and cost-effectiveness of prednisolone versus placebo for people with fibrotic hypersensitivity pneumonitis (FHP)? Background: FHP is a progressive fibrotic interstitial lung disease (ILD), which causes significant morbidity and mortality. Therapy choices for FHP are currently based on observational data and expert opinion. Despite a paucity of high-quality evidence, plus potential side effects, 97% of UK clinicians continue to regularly prescribe prednisolone Aims and objectives: The primary aim is to determine whether prescribing daily prednisolone, compared with placebo, reduces the deterioration of lung function in people recently diagnosed with FHP, as measured by change in forced vital capacity over a 6-month period. Secondary aims are to assess the effect of prednisolone at 6 months on other important outcomes: safety, ILD-specific and general health related quality of life, cough, hospitalisation and survival. We will also assess the cost-effectiveness of prednisolone vs placebo Methods: Double-blind, randomised (1:1) placebo-controlled, multi-centre, group-sequential, superiority trial, with internal pilot phase and parallel health economic evaluation. We will recruit people with FHP diagnosed within the last 6 months, not previously treated with prednisolone. We will exclude people on immunosuppressive therapy (including prednisolone) for any cause, and those with significant co-morbidities or a condition that might be significantly exacerbated by the administration of prednisolone. 222 participants will receive either oral prednisolone or matched placebo for 26 weeks. An initial peak dose of 40mg per day will be given for two weeks, followed by dose reduction of 10mg every 4 weeks until reaching a maintenance dose of 10mg, which will be continued for the remainder of the intervention period. There will then be a 9-week weaning period and final telephone call at study end (week 35). Lung function measurements will be performed on site at baseline, 3- and 6-months and participants will complete the King’s Brief Interstitial Lung Disease questionnaire, Leicester Cough Questionnaire and EQ-5D-5L. Participants will also complete a health/social care resource use questionnaire, based on the ModRUM core module. We will capture adverse events, FHP exacerbations, hospitalisations, and death throughout the study Timelines for delivery: This is a 51-month study. Trial set-up (M1-9); recruitment (M10-36, including internal pilot M10-M21); intervention and follow-up (M10-M43); final data cleaning, analysis, reporting and dissemination (M44-M51). Recruitment is estimated to take 27 months (mean 0.4 participants per site per month, up to 30 sites) Anticipated impact and dissemination: Dissemination will start at grant funding to raise awareness of the trial and continue until findings are adopted into clinical practice. Our PPIE group will work with Action for Pulmonary Fibrosis, British Thoracic Society, Asthma-Lung UK, Pulmonary Fibrosis Trust, EU-IPFF to ensure that physicians and patients, in the UK and internationally, are informed of the findings. As this is the first RCT of FHP therapy, the trial results will be of significant interest and will inform changes to national and international guidelines. The main results will be published in a high impact international journal; we anticipate subsequent publications will cover health economics, and treatment responses in disease subgroups