The effectiveness and risks of Treating people with Idiopathic Pulmonary fibrosis with the Addition of Lansoprazole (TIPAL): study protocol for a randomised placebo-controlled multicentre clinical trial

Abstract

Introduction: Idiopathic pulmonary fibrosis (IPF) is a chronic progressive fibrotic lung disease frequently complicated by gastro-oesophageal reflux disease. Although several observational studies and a pilot study have investigated the role of proton pump inhibitors (PPIs) in IPF, their efficacy is unknown and there is much debate in international IPF guidelines on their use. We aim to undertake an adequately powered double-blind placebo-controlled randomised multicentre clinical trial to assess the change in forced vital capacity (FVC), cough and other important patient-reported outcomes, following 12-month therapy with PPIs in people with IPF.

Methods and analysis: A total of 298 patients with IPF diagnosed by a multidisciplinary team according to international guidelines who are not receiving PPIs will be enrolled. Patients are randomised equally to receive two capsules of lansoprazole or two placebo capsules, two times per day for 12 months. The primary outcome for the trial is change in FVC, measured at home, between the first week and last week of the study period. Secondary assessments include cough frequency (in a subgroup) measured using the VitaloJAK cough monitor, the King's Brief Interstitial Lung Disease questionnaire, the Raghu Scale for Pulmonary Fibrosis, Medical Research Council dyspnoea score, EQ-5D-5L, Leicester Cough Questionnaire, modified DeMeester reflux symptoms questionnaire and opportunistically captured routine lung function measurements. High-resolution CT scoring will be undertaken in a subgroup. The trial is designed to determine whether treating people with IPF with lansoprazole will reduce the reduction in FVC over a year. The COVID-19 pandemic required the study to be undertaken as a remote trial.

Ethics and dissemination: This study received ethical approval from the East of England Cambridgeshire and Hertfordshire Research Ethics Committee (reference 20/EE/0043; integrated research application system number 269050). Trial results will be published in a peer-reviewed journal upon completion.

Trial registration number: ISRCTN13526307; ClinicalTrials.gov NCT04965298.

Keywords: Clinical Trial; Computed tomography; Pulmonary Disease.

Figure 1. TIPAL trial design. Flowcharts presenting an overview of the prerandomisation and postrandomisation tasks for TIPAL participants. Key: green steps=site led process; yellow steps=Norwich Clinical Trials Unit-led process; orange=participant process; pink=eCRF process/randomisation; blue=central pharmacy process; grey=follow-up visits to be conducted as per protocol. eCRF: electronic case report form, CT: computed tomography, h: hour, HRCT: high resolution computed tomography, M: month, IMP: investigational medicinal product, NCTU: Norwich Clinical Trials Unit, PPI: proton pump inhibitor, Pt: patient