A randomised placebo-controlled pilot trial of omeprazole in idiopathic pulmonary fibrosis (IPF)

INTERVENTION: Trade Name: Omeprazole (UK licensed generic product) Product Name: Omeprazole Pharmaceutical Form: Gastro‐resistant capsule, hard INN or Proposed INN: Omeprazole CAS Number: 73590‐58‐6 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 20‐ Pharmaceutical form of the placebo: Capsule, hard Route of administration of the placebo: Oral use CONDITION: Idiopathic Pulmonary Fibrosis (IPF) ; MedDRA version: 19.0 Level: PT Classification code 10021240 Term: Idiopathic pulmonary fibrosis System Organ Class: 10038738 ‐ Respiratory, thoracic and mediastinal disorders Therapeutic area: Diseases [C] ‐ Respiratory Tract Diseases [C08] PRIMARY OUTCOME: Main Objective: The principal question is whether omeprazole reduces cough (quantified objectively) in patients with IPF, when compared with placebo.; ; Primary end point(s): Primary Efficacy outcome:; ; Change in cough frequency between baseline and the end of treatment.; ; Feasibility outcomes :; ; • Rates of eligibility, recruitment, randomization and study completion; • Feasibility and acceptability of trial procedures; Secondary Objective: Secondary questions include whether omeprazole (as compared with placebo):; ‐ causes less acid reflux and non‐acid reflux; ‐ reduces symptoms of cough and reflux; ‐ makes any difference to lung function; ‐ reduces lung inflammation; ‐ is associated with a difference in the distance the patient can walk in 6 minutes; ‐ changes the frequency of lung infection; ‐ increases side effects. Timepoint(s) of evaluation of this end point: 3 months SECONDARY OUTCOME: Secondary end point(s): The following outcomes, proposed as secondary efficacy outcomes for any future trial, will be measured, with the focus of analysis being on data yield and quality; ; • Change in symptoms of cough at the end of treatment ; • Change in symptoms of reflux at the end of treatment; • Change in acid and non‐acid reflux after treatment; • Change in VC and Tco at the end of treatment; • Change in 6 minute walk distance at the end of treatment; • Markers of lung inflammation in bronchoalveolar lavage (BAL) fluid at the end of treatment (eg concentration of transforming growth factor beta, interleukin‐8 etc); • Change in lung infection in BAL fluid at the end of treatment; • Patient‐reported adverse events; Timepoint(s) of evaluation of this end point: 3 months INCLUSION CRITERIA: A pragmatic clinical definition of IPF will be used, in which recruited patients must fulfill all of the following criteria • IPF is considered the most likely diagnosis by the regional interstitial lung disease multidisciplinary team meeting (ILD‐MDT) • history of cough, with or without exertional dyspnoea • high resolution computed tomography (HRCT) scan features of honeycombing in a predominantly basal and subpleural distribution • bibasal crackles on auscultation • features of a restrictive ventilatory defect (vital capacity (VC) <90% predicted and/or diffusion factor for carbon monoxide (Tco) <90% predicted) • aged 40‐85 years Patients with radiological emphysema will be eligible so long as the diagnosis of IPF is secure, ie all the features above are satisfied. If the regional ILD‐MDT cannot reach a clear consensus as to the diagnosis, the case will be referred to 2 experts in ILD from outside the region, and the patien