Title: Treating idiopathic pulmonary fibrosis with the addition of lansoprazole
Funder: Department of Health and Social Care

Abstract: Pulmonary fibrosis is a progressive scarring condition of the lungs causing people to cough and become breathless. People with pulmonary fibrosis often have reflux disease which means that acid from the stomach may be breathed into the lungs and potentially damage them. Medicines which stop the stomach producing acid, called proton pump inhibitors (or PPIs), can be used to reduce reflux symptoms including heartburn. Some researchers have suggested that PPIs also reduce the progression of pulmonary fibrosis. _x000D_ _x000D_ The aim of this research is to see if pulmonary fibrosis progresses more slowly if people are treated with PPIs. Based on the results of the study, we will be able to recommend whether or not people with pulmonary fibrosis should take PPIs. _x000D_ _x000D_ We plan to undertake a large clinical trial. We will identify 298 people with a confirmed diagnosis of pulmonary fibrosis from at least 30 hospitals in the UK. At the beginning of the study, we will ask all patients to perform breathing tests, and we will ask those with a cough to use an electronic recording device to count the number of times they cough in a day as a sub-study. Cough frequency will be recorded again 3 months after starting the study. _x000D_ _x000D_ We will also ask them to complete two questions to rate their coughing and breathlessness, and answer questionnaires about how they feel about their coughing, pulmonary fibrosis, heartburn and general condition. People will then be given treatment with a PPI, called lansoprazole, or dummy tablets, twice per day, taken at least 30 minutes before meals, every day for 12 months. They will also be given a leaflet telling them what to do about reflux symptoms. In total, there will be five study visits, at 3 monthly intervals. At the end of the study, we will repeat all of these tests, and we’ll also ask all participants about their experience of taking their trial treatment, and analyse the results. We will also keep an eye out for any side effects that people may get because of the treatments including chest infections, diarrhoea or low magnesium levels. If people suffer from side effects, or if patients or their doctors choose, they will be able to reduce the dose._x000D_ _x000D_ People taking medicines that interact with PPIs or have other serious medical conditions will not be able to take part. People who are receiving PPIs will be able to join the study only if they can stop taking their medications without their heartburn returning._x000D_ We have consulted people living with pulmonary fibrosis in planning this study. Based on this, we have checked that:_x000D_ • the questionnaires are ‘user friendly’ and can be completed easily; _x000D_ • people are happy to use the cough counter as they did this successfully in an earlier smaller study;_x000D_ • taking twice daily treatment is also acceptable. _x000D_ _x000D_ Action for Pulmonary Fibrosis (AFP), the national pulmonary fibrosis patient charity, will support our study by working with us to design and run an add-on study to see if patients themselves can help recruit others into research studies. People living with pulmonary fibrosis have been involved in designing this study and will continue to provide advice during our study alongside other people from AFP. _x000D_ _x000D_ The study will be undertaken by doctors and researchers with experience of pulmonary fibrosis, reflux disease, PPIs and coughing. We are confident that we will be able to find out whether PPIs should be used by patients with pulmonary fibrosis. We will widely publicise our results with the help of APF. We will write reports for medical publications, media articles and use social media. Hopefully, as a result of the study, treatment guidelines will be changed as appropriate.

Lay abstract: Research Question: Does anti-reflux therapy slow the deterioration of lung function and improve morbidity in Idiopathic Pulmonary Fibrosis (IPF)?_x000D_ _x000D_ Background: IPF, a progressive fibrotic interstitial lung disease, has a poor prognosis and limited treatment options. Observational data suggest that anti-acid therapy is beneficial in IPF and current international guidelines cautiously advise their use. There are no randomised controlled trials of anti-acid therapy but all reviews advocate one._x000D_ _x000D_ Aims and Objectives: The main aim of this study is to determine whether, in people with IPF, lansoprazole 30mg twice daily reduces the deterioration in lung function compared with placebo, in terms of change in percentage predicted forced vital capacity (%FVC) over a 12 month period. Secondary aims are to determine the effect of lansoprazole on morbidity and other clinically important outcomes including cough, health related quality of life (HRQOL), breathlessness, hospitalisation and survival at 12 months. _x000D_ _x000D_ Design: A double-blind, 1:1 randomised placebo-controlled, two-arm parallel group, phase 3 multi-centre effectiveness study of an investigational medicinal product. In addition, an integrated study within a trial (SWAT), supported by Action for Pulmonary Fibrosis (APF), will be conducted to explore the influence of patient support groups on research recruitment and retention._x000D_ _x000D_ We will enrol 298 people with IPF diagnosed according to international criteria. Participants may be receiving a licensed anti-fibrotic medication or antacids and/or raft alginates. People with concomitant use of a proton pump inhibitor (PPI) or pro-kinetics, significant other comorbidity, allergy to PPIs or therapy interacting with PPIs will be excluded. Potential participants receiving PPIs may proceed to randomisation if they remain asymptomatic of reflux after a 2 week washout period._x000D_ _x000D_ Patients will receive either oral lansoprazole 30 mg (as 2 x 15mg tablets) to be taken twice daily, at least 30 minutes before meals, for 12 months or matched placebo (2 tablets) to be taken twice daily, at least 30 minutes before meals, for 12 months. The trial treatment dose may be reduced to one tablet (1 x 15mg lansoprazole or 1 placebo tablet) twice daily, at least 30 minutes before meals, in those developing adverse reactions (suspected or confirmed diagnoses of respiratory tract infection and pneumonia, Clostridium difficile infection and hypomagnesaemia). Treatments will be given in addition to standard care as defined by National Institute for Health and Clinical Excellence (NICE) guidelines (www.nice.org.uk/CG163). _x000D_ _x000D_ At baseline and 3-monthly during study participation, we will capture cough score, Leicester Cough Questionnaire, Kings Brief ILD questionnaire, Medical Research Council Dyspnoea Scale and EQ5D-5L. In addition, we will also collect responses to a validated reflux questionnaire and a non-validated lifestyle questionnaire at baseline and 12 months. Participants will also be asked to review the acceptability of their trial treatment at 12 months only. Lung function assessments including spirometry and gas transfer measurements will be measured at baseline, 3, 6 and 12 months post-randomisation. Objective cough frequency (in those with a cough) will be measured over a 24 hour period at baseline and 3 months as a sub-study. We will capture adverse events, hospitalisations and deaths throughout the trial. We will utilise the BTS IPF registry to capture relevant study data._x000D_ Timelines for delivery: We will allow six months for agreeing contracts and site initiation in 30 sites. We anticipate recruitment will take 26 months (0.35 participants per site per month). There will be a 12-month follow up period and it will take four months for data cleaning, analysis, reporting and dissemination._x000D_ _x000D_ Dissemination: This will start at grant funding and continue until the findings are adopted into clinical practice. We will publicise important landmarks during the study through lay press and social media. We will publish the study protocol and present the study findings at scientific meetings and in a peer-reviewed journal. We will work with APF to ensure that patients are aware of the findings, and guideline committees to ensure that guidelines and practice are changed, as appropriate.

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: RESPIRATORY