Condition category
Respiratory
Date applied
10/02/2020
Date assigned
25/02/2020
Last edited
15/10/2020
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Not yet recruiting

Plain English Summary

Background and study aims
Idiopathic pulmonary fibrosis (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 that stop stomach acid production, including 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, the researchers will be able to recommend whether or not IPF patients should take PPIs.

Who can participate?
Patients aged 40 years or above with a diagnosis of idiopathic pulmonary fibrosis. 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.

What does the study involve?
At the beginning of the study, the researchers will ask patients to perform breathing tests, and ask those with a cough to use a device to count the number of times they cough in 24hours. The researchers 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, the researchers will repeat these tests and analyse the results. The researchers will record any side effects people may get. If people suffer side effects, they can reduce the dose.

What are the possible benefits and risks of participating?
Benefits: There is no guarantee that the study will help participants personally, but the information we get from this study will improve our ability to treat patients with pulmonary fibrosis in the future.
Risks: Participants may not get the active treatment, lansoprazole, and may receive the dummy treatment, placebo. However participants will still receive any approved treatment for pulmonary fibrosis from their doctor. Participants will need to attend the hospital for visits in addition to their routine clinic visits. Although participants will receive reimbursement for their travel expenses up to £100 in total for trial participation. The blood tests may cause discomfort and bruising. Questionnaires will take time to complete. Breathing tests may cause slight breathlessness, difficulty breathing or chest discomfort for a few minutes at the most following the tests. Participants may experience side effects from the active treatment. However, participants are free to reduce their dose of trial treatment under the guidance of their doctor/research team. Participants are also free to withdraw from the study at any time without giving a reason and without any effect on the standard of care participants receive.

Where is the study run from?
Norfolk and Norwich University Hospitals NHS Foundation Trust (UK)

When is the study starting and how long is it expected to run for?
March 2020 to May 2022

Who is funding the study?
NIHR Evaluation, Trials and Studies Co-ordinating Centre (NETSCC) (UK)

Who is the main contact?
Megan Jones
megan.l.jones@uea.ac.uk

Trial website

Contact information

Type

Public

Primary contact

Miss Megan Jones

ORCID ID

Contact details

NCTU
Norwich Medical School
University of East Anglia
Norwich
NR4 7TJ
United Kingdom
+44 (0)1603591224
megan.l.jones@uea.ac.uk

Type

Scientific

Additional contact

Prof Andrew Wilson

ORCID ID

Contact details

Norwich Medical School
University of East Anglia
Floor 2 Bob Champion Research and Education Building
Norwich
NR4 7TJ
United Kingdom
+44 (0)1603 591257
a.m.wilson@uea.ac.uk

Additional identifiers

EudraCT number

2020-000041-14

ClinicalTrials.gov number

Nil known

Protocol/serial number

CPMS 44455, IRAS 269050

Study information

Scientific title

The effectiveness and risks of Treating people with Idiopathic Pulmonary fibrosis with the Addition of Lansoprazole (TIPAL): a randomised placebo-controlled multi-centre clinical trial

Acronym

TIPAL

Study hypothesis

Participants treated with lansoprazole will have a smaller absolute decline in percentage predicted (%) FVC at 12 months post-randomisation versus participants treated with placebo.

Ethics approval

Approved 29/04/2020, East of England - Cambridgeshire and Hertfordshire Research Ethics Committee (The Old Chapel, Royal Standard Place, Nottingham, NG1 6FS, UK; +44 (0)207 104 8106; nrescommittee.eastofengland-cambsandherts@nhs.net), ref: 20/EE/0043

Study design

Interventional randomized controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet.

Condition

Idiopathic pulmonary fibrosis

Intervention

This project is a clinical trial of an investigational medicinal product (drug). The drug (lansoprazole) 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 (although the doctors will be able to find out in an emergency). The researchers will be running the study at approximately 37 hospitals across the UK.

Potentially eligible patients will be approached in clinic or identified from local patient lists/databases. They will be given 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 24 h to consider participating.

Interested patients will be invited to a 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 a lung function assessment (including spirometry and gas transfer assessments) and provide a blood sample for safety in order for the investigator to confirm their eligibility for the trial. Patients will also provide a blood sample for analysis in future research, a blood sample for genotype analysis and complete a 24-h 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 2-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 min before meals, for 12 months.

At 3 months post-randomisation, participants will attend the study site again to complete the relevant questionnaires, provide blood samples for safety checks, complete lung function assessments (including spirometry and gas transfer assessments) as before. Participants involved in the sub-study will again undergo cough frequency monitoring, and activity and sleep monitoring if applicable, for a final 24-h 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 attend the site again at 6 months post-randomisation where they will be required to complete questionnaires, provide a safety blood sample and complete lung function assessments (including spirometry and gas transfer assessments). 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 via a pill count completed by local site staff. A final supply of trial medication will be dispensed to the patient with the appropriate dosing instructions.

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

The final study visit occurs 12 months post-randomisation. Patients will be required to complete all necessary questionnaires, provide a blood sample for safety analysis and complete lung function assessments (including spirometry and gas transfer assessments). Participants will also have an additional blood sample taken for analysis in future research studies. 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 min before meals: respiratory tract infection including pneumonia, Clostridium difficile infection and/or hypomagnesaemia. Participants may also reduce dose if the participant or clinician wishes them to do so.

Intervention type

Drug

Phase

Phase III

Drug names

Lansoprazole

Primary outcome measure

Predicted (%) forced vital capacity (FVC) at 12 months post-randomisation

Secondary outcome measures

1. Cough frequency measured using a VitaloJAK cough monitor over a 24-h period at baseline and 3 months post-randomisation
2. Cough score measured using a 100-mm visual analogue scale (VAS) at baseline 3, 6, 9 and 12 months post-randomisation
3. Cough related quality of life measured by the Leicester Cough Questionnaire at baseline, 3, 6, 9 and 12 months post-randomisation
4. Breathlessness measured by the Medical Research Council (MRC) Dyspnoea Scale at baseline, 3, 6, 9 and 12 months post-randomisation
5. Disease specific quality of life measured using the King’s Brief Interstitial Lung Disease (K-BILD) questionnaire at baseline, 3, 6, 9 and 12 months post-randomisation
6. Health related quality of life measured using the EQ-5D-5L questionnaire at baseline, 3, 6, 9 and 12 months post-randomisation (quality-adjusted life-years will be estimated)
7. Adverse events with particular relevance to respiratory tract infection including pneumonia, Clostridium difficile infection and hypomagnesaemia measured at 3, 6, 9 and 12 months post-randomisation
8. Total lung diffusing capacity of carbon monoxide (DLCO) measured at baseline, 3, 6 and 12 months post-randomisation
9. Sleep quality measured by the short Pittsburgh Sleep Quality Index at baseline, 3 and 12 months post-randomisation
10. Reflux characteristics measured by the DeMeester score at baseline, 3 and 12 months post-randomisation
11. Participant acceptability of trial treatment measured by a non-validated study-specific questionnaire at 12 months post-randomisation
12. Risk of sleep apnoea measured by the STOP-bang questionnaire at 12 months post-randomisation
13. Progression free survival (with progression defined as all-cause death, lung transplant, a 10% reduction in FVC % predicted from baseline, or 15% reduction in DLCO % predicted from baseline) at 12 months post-randomisation
14. Hospital-free survival defined as death (all causes) or first non-elective (all-cause) hospital admission at 12 months post-randomisation
15. Respiratory related hospital-free survival at 12 months post-randomisation

Overall trial start date

01/09/2019

Overall trial end date

31/08/2023

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. Male or female, aged greater than or equal to 40 years
2. A diagnosis of Idiopathic Pulmonary Fibrosis (IPF) based on local or regional multi-disciplinary consensus according to the latest international guidelines (Am J Respir Crit Care Med. 2018;198:e44-e68)
3. Patients may be receiving licensed anti-fibrotic medication (for at least 4 weeks prior to randomisation with no planned amendments for at least 4 weeks post-randomisation)
4. Able to provide informed consent

Additional inclusion criteria for cough count sub-study:
1. Pre-existing diagnosis of persistent cough (defined as troublesome for more than 8 weeks prior to study enrolment)

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 298; UK Sample Size: 298

Participant exclusion criteria

1. Patients unable to complete reliable FVC measurements (i.e. the difference between the two largest values is NOT < = 0.150 L)
2. Concomitant use of a proton pump inhibitor (PPI) or prokinetic drugs (cisapride, domperidone, metoclopramide, erythromycin, pruclopride etc) within 2 weeks prior to randomisation
3. 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 requiring antimicrobial therapy)
4. Significant co-existing respiratory disease (defined as a respiratory condition that exhibits a clinically relevant effect on respiratory symptoms and disease progression as determined by the PI). The presences of bronchiectasis is permitted
5. Patients with FEV1/FVC< 0.7
6. Significant medical, surgical or psychiatric disease that in the opinion of the patient's attending physician would affect subject safety or influence the study outcomes including liver failure (e.g. serum transaminase > 2x upper limit of normal (ULN), bilirubin > 1.5x ULN (unless the patient has Gilbert's syndrome) and chronic kidney disease (CKD) no greater than stage 3 (stable for at least 3 months prior to enrolment), erosive oesophagitis, Barrett's oesophagus or any other condition requiring lifelong proton pump inhibitor use.
7. Known allergy to proton pump inhibitors or the contents of placebo
8. Concomitant use of atazanavir, ketoconazole, itraconazole, tacrolimus, methotrexate, fluvoxamine (see section 6.4.5 of protocol)
9. Females who are of childbearing potential or lactating. Non-childbearing potential is defined as follows: postmenopausal females who have had at least 12 months of spontaneous amenorrhoea or 6 months of spontaneous amenorrhoea with serum FSH> 40mlU/ml or females who have had a hysterectomy, bilateral salpingectomy or bilateral oophorectomy at least 6 weeks prior to enrolment
10. Receipt of another investigational drug or biological agent associated with another clinical trial within the 4 weeks prior to TIPAL study enrolment or 5 times the drug half-life, whichever is the longer
11. Receiving long-term oxygen therapy
12. Patients with hypomagesmesmia (defined as magnesium < = 0.6mmol/L)

Recruitment start date

01/01/2021

Recruitment end date

31/05/2022

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Norfolk and Norwich University Hospital
Colney Lane
Norwich
NR4 7UY
United Kingdom

Trial participating centre

Queen Elizabeth Hospital Birmingham
University Hospitals Birmingham NHS Foundation Trust Mindelsohn Way
Birmingham
B15 2TH
United Kingdom

Trial participating centre

Central Manchester University Hospitals NHS Foundation Trust
Cobbett House Oxford Road
Manchester
M13 9WL
United Kingdom

Trial participating centre

University Hospital Aintree
Aintree University Hospital Nhs Foundation Trust Fazakerley Hospital Lower Lane Liverpool Merseyside
Liverpool
L9 7AL
United Kingdom

Trial participating centre

Royal Papworth Hospital Nhs Foundation Trust
Papworth Everard
Cambridge
CB23 3RE
United Kingdom

Trial participating centre

Royal Brompton Hospital
Royal Brompton and Harefield NHS Foundation Trust Sydney Street
London
SW3 6NP
United Kingdom

Trial participating centre

Freeman Hospital
Freeman Road High Heaton
Newcastle upon Tyne
NE7 7DN
United Kingdom

Trial participating centre

Western Health & Social Care Trust
MDEC Building Glenshane Road
Derry
BT47 6SB
United Kingdom

Trial participating centre

Walsgrave General Hospital
Clifford Bridge Road
Coventry
CV2 2DX
United Kingdom

Trial participating centre

NHS Forth Valley
33 Spittal Street
Stirling
FK8 1DX
United Kingdom

Trial participating centre

Leicester Royal Infirmary
Infirmary Square
Leicester
LE1 5WW
United Kingdom

Trial participating centre

Westmorland General Hospital
University Hospitals of Morecambe Bay NHS Foundation Trust Burton Road
Kendal
LA9 7RG
United Kingdom

Trial participating centre

Southmead Hospital
North Bristol NHS Trust Southmead Road Westbury-on-trym
Bristol
BS10 5NB
United Kingdom

Trial participating centre

New Cross Hospital
The Royal Wolverhampton Nhs Trust Wolverhampton Road Heath Town
Wolverhampton
WV10 0QP
United Kingdom

Trial participating centre

Northern General Hospital
Sheffield Teaching Hospitals Nhs Foundation Trust Herries Road
Sheffield
S5 7AU
United Kingdom

Trial participating centre

South Tyneside District Hospital
South Tyneside Nhs Foundation Trust Harton Lane
South Shields
NE34 0PL
United Kingdom

Trial participating centre

Worcestershire Royal Hospital
Worcestershire Acute Hospitals Nhs Trust Charles Hastings Way
Worcester
WR5 1DD
United Kingdom

Trial participating centre

Queen Elizabeth Hospital
Gateshead Health Nhs Foundation Trust
Gateshead
NE9 6SX
United Kingdom

Trial participating centre

Sherwood Forest Hospitals Nhs Foundation Trust
Mansfield Road
Sutton-in-Ashfield
NG17 4JL
United Kingdom

Trial participating centre

St George's Hospital
St George's University Hospitals Nhs Foundation Trust Blackshaw Road
London
SW17 0QT
United Kingdom

Trial participating centre

Victoria Hospital
Blackpool Teaching Hospitals Nhs Foundation Trust Whinney Heys Road
Blackpool
FY3 8NR
United Kingdom

Trial participating centre

St. Marys Hospital
Imperial College Healthcare Nhs Trust Praed Street
London
W2 1NY
United Kingdom

Trial participating centre

Nhs Grampian
Summerfield House 2 Eday Road
Aberdeen
AB15 6RE
United Kingdom

Trial participating centre

Southampton General Hospital
University Hospital Southampton Nhs Foundation Trust Tremona Road
Southampton
SO16 6YD
United Kingdom

Trial participating centre

Leighton Hospital
Mid Cheshire Hospitals Nhs Foundation Trust Leighton
Crewe
CW1 4QJ
United Kingdom

Trial participating centre

Royal Preston Hospital
Lancashire Teaching Hospitals Nhs Foundation Trust Sharoe Green Lane Fulwood
Preston
PR2 9HT
United Kingdom

Trial participating centre

Hull Royal Infirmary
Hull and East Yorkshire Hospitals Nhs Trust Anlaby Road
Hull
HU3 2JZ
United Kingdom

Trial participating centre

Shrewsbury And Telford Hospital Nhs Trust
Mytton Oak Road
Shrewsbury
SY3 8XQ
United Kingdom

Trial participating centre

Cardiff & Vale University LHB
Heath Park
Cardiff
CF14 4XW
United Kingdom

Trial participating centre

John Radcliffe Hospital
Oxford University Hospitals Nhs Foundation Trust Headley Way Headington
Oxford
OX3 9DU
United Kingdom

Trial participating centre

Royal Infirmary
Calderdale and Huddersfield Nhs Foundation Trust Acre Street
Huddersfield
HD3 3EA
United Kingdom

Trial participating centre

University College London Hospitals Nhs Foundation Trust
250 Euston Road
London
NW1 2PG
United Kingdom

Trial participating centre

Queens Medical Centre
Nottingham University Hospitals Nhs Trust Derby Road
Nottingham
NG7 2UH
United Kingdom

Trial participating centre

University Hospitals of North Midlands Nhs Trust
Newcastle Road
Stoke-on-Trent
ST4 6QG
United Kingdom

Trial participating centre

The Royal London Hospital
Barts Health Nhs Trust Whitechapel
London
E1 1BB
United Kingdom

Sponsor information

Organisation

Norfolk and Norwich University Hospitals NHS Foundation Trust

Sponsor details

Colney Lane
Colney
Norwich
NR4 7UY
United Kingdom
+44 (0)1603 647882
julie.dawson@nnuh.nhs.uk

Sponsor type

Hospital/treatment centre

Website

http://www.nnuh.nhs.uk/

Funders

Funder type

Government

Funder name

NIHR Evaluation, Trials and Studies Co-ordinating Centre (NETSCC); Grant Codes: NIHR127479

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

National Institute for Health Research (NIHR) (UK)

Alternative name(s)

NIHR

Funding Body Type

government organisation

Funding Body Subtype

National government

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Planned publication in a high-impact peer-reviewed journal.

IPD sharing statement:
The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

Intention to publish date

31/08/2024

Participant level data

Available on request

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

15/10/2020: The recruitment start date was changed from 01/10/2020 to 01/01/2021. 29/07/2020: The following changes were made to the trial record: 1. The ethics approval was added. 2. The recruitment start date was changed from 31/03/2020 to 01/10/2020. 13/02/2020: Trial’s existence confirmed by National Institute for Health Research (NIHR).