Randomised, double-blind, placebo-controlled pilot trial of omeprazole in idiopathic pulmonary fibrosis

Abstract

BackgroundCough is a common, disabling symptom of idiopathic pulmonary fibrosis (IPF), which may be exacerbated by acid reflux. Inhibiting gastric acid secretion could potentially reduce cough. This study aimed to determine the feasibility of a larger, multicentre trial of omeprazole for cough in IPF, to assess safety and to quantify cough.MethodsSingle-centre, double-blind, randomised, placebo-controlled pilot trial of the proton pump inhibitor (PPI) omeprazole (20 mg twice daily for 3 months) in patients with IPF. Primary objectives were to assess feasibility and acceptability of trial procedures. The primary clinical outcome was cough frequency.ResultsForty-five participants were randomised (23 to omeprazole, 22 to placebo), with 40 (20 in each group) having cough monitoring before and after treatment. 280 patients were screened to yield these numbers, with barriers to discontinuing antacids the single biggest reason for non-recruitment. Recruitment averaged 1.5 participants per month. Geometric mean cough frequency at the end of treatment, adjusted for baseline, was 39.1% lower (95% CI 66.0% lower to 9.3% higher) in the omeprazole group compared with placebo. Omeprazole was well tolerated and adverse event profiles were similar in both groups, although there was a small excess of lower respiratory tract infection and a small fall in forced expiratory volume and forced vital capacity associated with omeprazole.ConclusionsA large randomised controlled trial of PPIs for cough in IPF appears feasible and justified but should address barriers to randomisation and incorporate safety assessments in relation to respiratory infection and changes in lung function.

Design and rationale of a multi-center, pragmatic, open-label randomized trial of antimicrobial therapy – the study of clinical efficacy of antimicrobial therapy strategy using pragmatic design in Idiopathic Pulmonary Fibrosis (CleanUP-IPF) clinical trial

“…As a result, the majority of Phase II and III clinical trials in IPF have used the measure of lung function as the primary endpoint. Recently, there has been considerable work on quality of life and symptoms (including cough and reflux) [59]. Furthermore, several groups have pooled clinical trial databases to examine treatment effects of drugs on clinical endpoints including mortality and respiratory hospitalizations [60,61].…”

Comorbidities in idiopathic pulmonary fibrosis: an underestimated issue

“…Moreover, a cough trial with proton pump inhibitors showed that proton pump inhibitors increase the nonacidic components of reflux [137]. A recently published pilot trial on omeprazole in IPF demonstrated that omeprazole is well tolerated; a small excess of lower respiratory tract infection was evidenced together with a minor reduction in FVC associated with use of omeprazole [138]. In order to give a definitive answer on the effects of GOR therapy in patients with IPF, further prospective, randomised studies are needed to shed light on this specific aspect.…”

Guidelines of the Polish Respiratory Society for Diagnosis and Treatment of Idiopathic Pulmonary Fibrosis

“…No changes were observed in FVC, T L,CO or quality of life assessments during three months of follow-up. The study results can support the efficacy of omeprazole in managing cough in IPF patients and indicate a need of additional, multicentre trials with larger patient populations [280].…”