Clinical trial NCT02085018: Pilot Trial Of Omeprazole in Idiopathic Pulmonary Fibrosis (IPF)
Official title: A Randomised, Placebo-controlled Trial of Omeprazole in Idiopathic Pulmonary Fibrosis (IPF)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Idiopathic Pulmonary Fibrosis
Keywords: omeprazole, idiopathic pulmonary fibrosis
Lead sponsor: Newcastle-upon-Tyne Hospitals NHS Trust
Sponsor class: OTHER
Collaborators: name: Newcastle University
First posted: 2014-03-12
Enrollment: 45
Sex: ALL
Minimum age (years): 40
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: objectively measured cough frequency
timeFrame: 90 days
Secondary outcomes:
measure: symptoms of cough
timeFrame: 90 days
measure: reflux symptoms
timeFrame: 90 days
measure: acid and non-acid reflux
timeFrame: 90 days
measure: vital capacity (VC) & transfer factor for carbon monoxide (Tco)
timeFrame: 90 days
measure: 6 minute walk distance
timeFrame: 90 days
measure: assess amount of inflammation in lung
timeFrame: 90 days
measure: lung infection rate
timeFrame: 90 days
measure: adverse events rate
timeFrame: 90 days
Other outcomes:
measure: rate of recruitment
timeFrame: 18 months
measure: rate of study completion
timeFrame: 18 months
Locations:
city: Newcastle upon Tyne
country: United Kingdom
facility: The Newcastle upon Tyne Hospitals NHS Foundation Trust
state: Tyne & Wear
Study officials:
affiliation: Newcastle University
name: John Simpson, FRCP
role: STUDY_DIRECTOR
affiliation: Newcastle upon Tyne Hospitals NHS Foundation Trust
name: Ian Forrest, MRCP
role: PRINCIPAL_INVESTIGATOR
References: