Pilot Trial Of Omeprazole in Idiopathic Pulmonary Fibrosis (IPF) (PPIPF)

A Randomised, Placebo-controlled Trial of Omeprazole in Idiopathic Pulmonary Fibrosis (IPF)

Idiopathic pulmonary fibrosis (IPF) is a disease of unknown cause in which areas of normal lung tissue are replaced by scars. As a result it becomes harder for the lungs to extract oxygen from the air. IPF is commonly progressive, and around 50% of patients diagnosed with the disease die after approximately 3 years. The most common, troublesome symptoms of IPF are breathlessness on exertion, and cough. No drug treatments have been unequivocally shown to improve the death rate, or to significantly impact upon symptoms, in IPF.

In recent years it has been recognised that cough can be caused by small amounts of liquid coming up from the stomach and "going down the wrong way" into the lungs, a process commonly known as "reflux". As liquid in the stomach is usually acidic, patients' lungs may repeatedly be exposed to small amounts of acid. Reflux is unusually common in IPF and could potentially contribute to the debilitating cough found with the disease. However there are many potential causes for cough in IPF.

Stomach acid can be efficiently "switched off" by drugs called "proton pump inhibitors", one of which is called omeprazole. If reflux of stomach acid does contribute to cough in IPF, omeprazole might be expected to reduce cough. The purpose of this study is therefore to test whether omeprazole does reduce cough in patients with IPF. Sixty patients with IPF will be randomly allocated to have 3 months of omeprazole or a placebo. Neither the patient nor the doctor will be aware which treatment has been given, ie this is a randomised "double-blind", placebo--controlled trial. Patients' cough frequency will be measured before and after treatment and the change in cough frequency compared in those receiving omeprazole and those receiving placebo. Change in cough frequency is the main thing we aim to compare, but a range of other measurements will be assessed such as the numbers of patients eligible to take part, agreeing to randomisation and providing outcome data, patients' lung function, symptom scores, the amount of reflux, and the amount of inflammation in the lungs.

Study Overview

• Status: Completed
• Conditions: Idiopathic Pulmonary Fibrosis
• Intervention / Treatment: Drug: Omeprazole; Drug: Matched placebo

• Study Type: Interventional
• Enrollment (Actual): 45
• Phase: Phase 2

Contacts and Locations

Study Locations

• United Kingdom
  • Tyne & Wear
    • Newcastle upon Tyne, Tyne & Wear, United Kingdom, NE1 4LP
      • The Newcastle upon Tyne Hospitals NHS Foundation Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 38 years to 83 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion 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 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 taking short courses (eg. 2 months) of proton pump inhibitors (PPI) will be eligible once the treatment has been discontinued for a minimum of 1 month.

Exclusion Criteria:

• Known allergy to Omeprazole or other proton pump inhibitor.
• Concomitant use of warfarin, diazepam, phenytoin, ketoconazole.
• Concomitant use of a regular PPI, antacid, prokinetic or raft alginate during the trial period.
• History of upper respiratory tract infection, lower respiratory tract infection or exacerbation of IPF in the 4 weeks before starting study drugs.
• Active trial of treatment for IPF 9eg. prednisolone, pirfenidone, N-acetylcysteine) started in the 4 weeks before starting study drugs.
• Documented history of hepatic cirrhosis.
• Pregnancy or lactation.
• ILD-MDT considers the most likely cause of he patient's ILD to be a condition other than IPF (eg. rheumatoid lung, systemic sclerosis ILD, asbestosis, chronic hypersensitivity pneumonitis, sarcoidosis, etc.).
• Concurrent enrolment in a trial of a Clinical Trial of Investigational Medicinal Product (CTIMP) for IPF.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Omeprazole; Omeprazole 20 milligrams twice a day taken for 90 days	Drug: Omeprazole; Drug; Other Names: Losec
Placebo Comparator: Matched placebo; Matched placebo twice a day taken for 90 days	Drug: Matched placebo; Matched placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
objectively measured cough frequency	the change in frequency of objectively measured cough from beginning of the study to the end of treatment (within 2 weeks of completion of treatment). This will be compared in the two groups.	90 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
symptoms of cough	change in symptoms of cough at the end of treatment as measured by validated cough questionnaire	90 days
reflux symptoms	change in symptoms of reflux as measured by validated questionnaires	90 days
acid and non-acid reflux	change in acid and non-acid reflux measured by oesophageal physiological study	90 days
vital capacity (VC) & transfer factor for carbon monoxide (Tco)	change in VC and Tco as measured by lung function tests	90 days
6 minute walk distance	change in 6 minute walk distance from baseline to 90 days	90 days
assess amount of inflammation in lung	assess markers of lung inflammation in bronchoalveolar lavage (BAL) fluid (eg. concentration of transforming growth factor beta, interleukin-8 etc.)	90 days
lung infection rate	assess bronchoalveolar lavage (BAL) fluid for infections over period from baseline to 90 days, also patient reported infection in adverse event diary	90 days
adverse events rate	patient reported adverse events, assess lung infection rate in bronchoalveolar fluids over period from baseline to 90 days	90 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
rate of recruitment	Number of participants eligible and consented for study	18 months
rate of study completion	Number of participants completing all study procedures (over 90 days for each participant)	18 months

Collaborators and Investigators

• Sponsor: Newcastle-upon-Tyne Hospitals NHS Trust
• Collaborators: Newcastle University
• Investigators: Study Director: John Simpson, FRCP, Newcastle University; Principal Investigator: Ian Forrest, MRCP, Newcastle upon Tyne Hospitals NHS Foundation Trust

Study record dates

Study Major Dates

• Study Start (Actual): March 28, 2014
• Primary Completion (Actual): September 27, 2016
• Study Completion (Actual): September 27, 2016

Study Registration Dates

• First Submitted: February 9, 2014
• First Submitted That Met QC Criteria: March 10, 2014
• First Posted (Estimate): March 12, 2014

Study Record Updates

• Last Update Posted (Actual): November 20, 2017
• Last Update Submitted That Met QC Criteria: November 17, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Keywords: omeprazole, idiopathic pulmonary fibrosis
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Fibrosis; Pulmonary Fibrosis; Idiopathic Pulmonary Fibrosis; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Gastrointestinal Agents; Anti-Ulcer Agents; Proton Pump Inhibitors; Omeprazole
• Other Study ID Numbers: IAFIPF001; 2013-003301-26 (EudraCT Number); IPFPSG12-7 (Other Grant/Funding Number: British Lung Foundation); 13/YH/0284 (Other Identifier: Research Ethics Committee)