Treating People With Idiopathic Pulmonary Fibrosis With the Addition of Lansoprazole

Phase

Condition

Cystic Fibrosis

Scar Tissue

Lung Disease

Treatment

Lansoprazole

Matched placebo

Clinical Study ID

NCT04965298

269050-80-06-19

2020-000041-14

269050

ISRCTN13526307

Ages > 40
All Genders

Study Summary

IPF is a progressive scarring lung condition causing coughing and breathlessness. IPF patients often have reflux disease meaning stomach acid may be breathed into the lungs, potentially damaging them. Medicines which stop stomach acid production, proton pump inhibitors (PPIs), can be used to reduce reflux symptoms including heartburn. Some researchers suggest PPIs also reduce IPF progression.

This research aims to see if IPF progresses slower if treated with PPIs. Based on the results, we will be able to recommend whether or not IPF patients should take PPIs.

This trial will involve 298 IPF patients from approximately 37 UK hospitals. At the beginning of the study, we will ask patients to start performing weekly breathing tests at home using equipment provided, and ask those with a cough to use a device to count the number of times they cough in 24hours. We will ask them to answer two questions rating their coughing and breathlessness, and complete questionnaires on their coughing, IPF, sleep habits and general condition. People will be given a PPI, called lansoprazole, or dummy tablets, twice per day for 12 months. They will be given a leaflet telling them what to do about reflux symptoms. At the end of the study, we will repeat these tests and analyse the results. We will record any side effects people may get. If people suffer side effects, they can reduce the dose.

People taking medicines that interact with PPIs or have other serious medical conditions won't be able to participate. People receiving PPIs will only be able to participate if they can stop taking their medication without their heartburn returning.

Eligibility Criteria

Inclusion

Inclusion Criteria:

Male or female, aged greater than or equal to 40 years.
A diagnosis of Idiopathic Pulmonary Fibrosis (IPF) based on local or regionalmulti-disciplinary consensus according to the latest international guidelines (50).
Patients may be receiving licensed anti-fibrotic medication (for at least 4 weeksprior to randomisation with no planned amendments for at least 4 weekspost-randomisation).
Able to provide informed consent. Additional Inclusion Criteria for cough count sub-study:
Pre-existing diagnosis of persistent cough (defined as troublesome for more than 8 weeksprior to study enrolment).

Exclusion

Exclusion Criteria:

Patients unable to comply with study assessments including the ability to completereliable spirometry assessments.
Concomitant use of a proton pump inhibitor (PPI) or prokinetic drugs (cisapride,domperidone, metoclopramide, erythromycin, prucalopride etc.) within 2 weeks prior torandomisation.
Patients with a self-reported respiratory tract infection within 4 weeks of screening (defined as two or more of: increased cough, sputum or breathlessness and requiringantimicrobial therapy).
Significant co-existing respiratory disease (defined as a respiratory condition thatexhibits a clinically relevant effect on respiratory symptoms and disease progressionas determined by the PI). The presence of traction bronchiectasis is permitted.
Patients with an FEV1/FVC<0.7.
Significant medical, surgical or psychiatric disease that in the opinion of thepatient's attending physician would affect subject safety or influence the studyoutcomes including liver failure (e.g. serum transaminase > 2 x upper limit of normal (ULN), Bilirubin > 1.5 x ULN (unless the patient has Gilbert's Syndrome) and chronickidney disease (CKD) greater than stage 3 , erosive oesophagitis, Barrett's oesophagusor any condition requiring lifelong proton pump inhibitor use.
Known allergy to proton pump inhibitors or the contents of placebo.
Concomitant use of atazanavir, ketoconazole, itraconazole, tacrolimus, methotrexate,fluvoxamine (see section 6.4.5).
Females who are of childbearing potential or lactating. A postmenopausal state isdefined as no menses for 12 months without an alternative medical cause. A high FSHlevel in the postmenopausal range may be used to confirm a post-menopausal state inwomen not using hormonal contraception or hormonal replacement therapy. However in theabsence of 12 months of amenorrhea, a single FSH measurement is insufficient.
Receipt of another investigational drug or biological agent associated with anotherclinical trial within the 4 weeks prior to TIPAL study enrolment or 5 times the drughalf-life, whichever is the longer.
Receiving long-term oxygen therapy.
Patients with hypomagnesemia (defined as magnesium ≤0.6 mmol/L).

Study Design

Lansoprazole

June 16, 2021

February 28, 2025

Study Description

Idiopathic pulmonary fibrosis (IPF) is a progressive and usually fatal lung disease with a poor prognosis. IPF patients frequently have other medical conditions as well, with reflux disease being one of the most common. Previous studies and a review of data already collected suggest that treatments used to reduce reflux disease symptoms, proton pump inhibitors (PPIs), may reduce IPF disease progression and improve survival rates. Current IPF treatment guidelines cautiously advise PPI treatment for IPF patients, however there hasn't been a study which investigates this specifically yet even though doctors and government groups have said one is needed. There are thought to be links between cough, reflux, sleep and IPF. As a result we will be asking a sub-group of patients to complete two 24 hour sessions of cough frequency monitoring as a sub-study. Some of these participants may be asked to wear a wrist-based activity and sleep monitor during these periods also. In addition, we will ask patients to complete two questionnaires on their sleeping habits to further investigate this link. At the end of the trial, we will able to recommend whether or not IPF patients should take PPIs routinely or not.

This project is a clinical trial of an investigational medicinal product (drug). The drug is well established and approved for use for another medical condition. The drug will be assessed against placebo (dummy) tablets, with patients allocated to either group by chance. Patients on the drug and dummy tablets will be assessed at the same time. Neither patients nor their doctors or the research team will know which treatment they have been allocated to. We will be running the study at approximately 37 hospitals across the UK.

All study visits may take place remotely without the participant needing to attend the hospital. However, face-to-face onsite visits are also permitted if preferred/feasible. All participants will receive central training via video call, with a trained clinical physiologist, following consent on how to complete domiciliary spirometry assessments. Further training will be provided during follow-up if deemed required following a review of the data. Questionnaires will be completed either electronically or by post.

Potentially eligible patients will be approached remotely or in clinic after being identified from local patient lists/databases. They will be given/sent the relevant study literature to consider participation in the study and will be followed-up by a member of the local research team after they have had at least 24hours to consider participating.

Interested patients will be invited to a virtual or face-to-face screening appointment where they will be counselled on the study and what it entails in order to provide informed consent to participate. The patient will then be asked to complete baseline questionnaires, provide demographic, medical history and concomitant medication, and any other relevant study information, complete spirometry assessments over 5 days at home using a domiciliary spirometer and provide a blood sample for safety in order for the investigator to confirm their eligibility for the trial. Patients may also provide a blood sample for analysis in future research if the visit takes place at the recruiting site. In addition, eligible participants may complete a 24hour period of cough frequency monitoring, and activity and sleep monitoring if applicable, if they have consented to do so. Patients in receipt of PPIs without a clear clinical indication for them at consent, will undergo a two week wash-out period (following agreement from the patient and their GP) to ascertain whether it is safe to stop this treatment and monitor whether their symptoms subside. Patients who remain asymptomatic at the end of this period will proceed to enter the study. For those whose symptoms return, PPI treatment will recommence and they will not enter the study. Once the results of all baseline assessments are known, patients will be randomised.

Participants will receive an initial 6 month supply of trial medication and be instructed to take 2 tablets twice daily (approximately 12 hours apart), 30 minutes before meals, for 12 months. Participants will commence weekly domiciliary spirometry assessments, for 12 months, from this point onwards.

At 3 months post-randomisation, participants will complete the relevant questionnaires and provide blood samples for safety checks. Domiciliary spirometry assessments remain ongoing. Participants involved in the sub-study will again undergo cough frequency monitoring, and activity and sleep monitoring if applicable, for a final 24 hour period. Patients will be asked to report any changes in their medical history, medication and any events which they have experienced since their last visit.

Participants will be contacted again at 6 months post-randomisation where they we will complete questionnaires and provide a safety blood samples. Domiciliary spirometry assessments remain ongoing. Participants will again be asked to report any changes in their medical history, medication and any events which they have experienced since their last visit. Participant adherence to the trial medication will be checked. A final supply of trial medication will be dispensed.

At 9 months post-randomisation, local site staff will contact patients to record any changes in their medical history, medication and any events experienced since their last visit. Patients will be required to complete the required questionnaires and provide a blood sample for safety checks.

The final study assessments will be at 12 months post-randomisation. Patients will be required to complete all necessary questionnaires, provide a blood sample for safety analysis and a final set of domiciliary spirometry assessments will occur over a 5 day consecutive period. If participants have consented to do so, an additional blood sample will be taken for analysis in future research studies if the visit occurs on site. Patients will be required to report any changes in their medical history, medication and any events they have experienced since their last report to site staff.

If participants are suspected of or confirmed to have experienced any of the following they may reduce the dose of their trial treatment, at any point during the study, to 1 tablet, twice daily (approximately 12 hours apart), 30 minutes before meals: infection including pneumonia, Clostridium difficile infection and/or hypomagnesaemia. Participants may also reduce dose if the participant or clinician wishes them to do so.

A blood sample for genotype analysis may be taken at any study timepoint which occurs face-to-face, if the participants consents to provide one. Safety blood samples will be taken at the participant's GP surgery where visits take place remotely. Remote follow-up may take place via video or phone call.

Connect with a study center

Norfolk and Norwich University Hospitals NHS Foundation Trust
Norwich, Norfolk NR4 7UY
United Kingdom
Active - Recruiting

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