Treating idiopathic pulmonary fibrosis with the addition of lansoprazole

Research Question: Does anti-reflux therapy slow the deterioration of lung function and improve morbidity in Idiopathic Pulmonary Fibrosis (IPF)? 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. 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. 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. 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. 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). 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. 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. 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.