|E.1 Medical condition or disease under investigation
|Medical condition(s) being investigated
|Idiopathic Pulmonary Fibrosis
|Medical condition in easily understood language
|Diseases [C] - Respiratory Tract Diseases [C08]
|E.1.2 Medical condition or disease under investigation
|Idiopathic pulmonary fibrosis
|System Organ Class
|10038738 - Respiratory, thoracic and mediastinal disorders
|Condition being studied is a rare disease
|E.2 Objective of the trial
|Main objective of the trial
|The principal research question of this study asks does lansoprazole slow the deterioration of lung function in idiopathic pulmonary fibrosis patients compared to placebo after 12 months. This will be assessed by the absolute change in percentage predicted (%) forced vital capacity (FVC).
|Secondary objectives of the trial
|How patients feel about their coughing and breathlessness, their general quality of life and their quality of life associated with their IPF will be assessed as secondary objectives.
We will also look at if there is a relationship between the number of times people cough, and their activity and sleep patterns, and the trial treatment over a 24 hour period.
Risk of sleep apnoea will be assessed by two questionnaires at the end of the study.
Patients will confirm if the trial treatment is acceptable through a lifestyle questionnaire.
Patients will report on their reflux symptoms/characteristics and sleep quality intermittently during their participation.
Another indicator of lung function, the total lung diffusing capacity of carbon monoxide (known as DLCO), will also be assessed where these tests have been completed.
We will also be assessing if lansoprazole causes more side effects than the placebo, if the trial treatment is acceptable to patients and how the trial treatment im
|Trial contains a sub-study
|Full title, date and version of each sub-study and their related objectives
|The TIPAL cough count, and activity and sleep if applicable, sub-study will be assessed as a secondary outcome outlined within the main trial protocol.
The relevant secondary outcome is cough frequency over measured using the VitaloJAK cough meter over a 24 hours period assessed at baseline and 3 months post-randomisation. In addition patients participating in the sub-study will also be invited to wear an wrist-based accelerometer during the monitoring period to investigate whether there is a relationship between cough, activity levels and sleep patterns in this patient group as an exploratory investigation.
|Principal 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)
|Principal exclusion criteria
|1) Patients unable to comply with study assessments including the ability to complete reliable spirometry assessments.
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 presence 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) greater than stage 3, 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. A post-menopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. However in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient.
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).
|E.5 End points
|Primary end point(s)
|Absolute change in percentage predicted (%) forced vital capacity (FVC) at 12 months post-randomisation comparing lansoprazole to placebo.
|Timepoint(s) of evaluation of this end point
|The primary outcome variable, forced vital capacity (FVC), will be measured daily for 5 days at baseline and 12 months post-randomisation to calculate an average of the best value undertaken each day.
FVC will also be observed at 3 and 6 months post-randomisation to assess if the effect of the intervention is constant over time or varies as time progresses.
|Secondary end point(s)
|The following secondary outcomes will be assessed:
- cough frequency measured by the VitaloJAK cough monitor over a 24 hour period
- cough score measured using a 100mm visual analogue scale
- cough related quality of life measured by the Leicester Cough Questionnaire
- breathlessness measured by the MRC dyspnoea scale
- disease specific quality of life measured by the King's Brief Interstitial Lung Disease questionnaire
- health related quality of life measured by the EQ5D-5L questionnaire (quality adjusted life years will be estimated)
- adverse events with particular relevance to respiratory tract infection including pneumonia, Clostridium difficile infection and hypomagnesaemia
- total lung diffusing capacity of carbon monoxide (DLCO) (corrected for haemoglobin) where possible
- laboratory assessment of FVC and FEV1 data where possible
- sleep quality measured by the short Pittsburgh Sleep Quality Index
- reflux characteristics measured by the DeMeester score
- participant acceptability measured by a study-specific lifestyle questionnaire
- risk of sleep apnoea measured by the STOP-Bang questionnaire
- progression free survival (with progression defined as time from randomisation to week of all-cause death, lung transplant, 10% reduction in FVC % predicted from baseline)
- hospital free survival defined as death (all-causes) or first non-elective (all-cause) hospital admission
- respiratory related hospital free survival
- decline and rate of decline in absolute %FVC based on %FVC measured weekly
|Timepoint(s) of evaluation of this end point
|The secondary outcomes will be assessed as follows:
- cough frequency at 3 months post-randomisation
- cough score, cough related quality of life (QoL), breathlessness, disease specific QoL, health related QoL, and adverse events at 3, 6, 9 and 12 months post-randomisation
- DLCO at 3, 6 and 12 months post-randomisation where possible
- laboratory assessed FVC and FEV1 at 3, 6 and 12 months where possible
- sleep quality and reflux characteristics at 3 and 12 months post-randomisation
- participant acceptability, risk of sleep apnoea, progression free survival, hospital free survival and respiratory related hospital free survival at 12 months post-randomisation
- decline and rate of decline of absolute %FVC weekly over the course of 12 months
|E.6 and E.7 Scope of the trial
|Scope of the trial
|Trial type and phase
|Human pharmacology (Phase I)
|First administration to humans
|Other trial type description
|Therapeutic exploratory (Phase II)
|Therapeutic confirmatory (Phase III)
|Therapeutic use (Phase IV)
|E.8 Design of the trial
| Comparator of controlled trial
|Other medicinal product(s)
|Number of treatment arms in the trial
The trial involves single site in the Member State concerned
| The trial involves multiple sites in the Member State concerned
|Number of sites anticipated in Member State concerned
|The trial involves multiple Member States
|Number of sites anticipated in the EEA
|E.8.6 Trial involving sites outside the EEA
|Trial being conducted both within and outside the EEA
|Trial being conducted completely outside of the EEA
|Trial has a data monitoring committee
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|The end of the trial is defined as 4 months following the last follow-up visit of the last patient randomised to allow for data entry and data cleaning activities to be completed.
|E.8.9 Initial estimate of the duration of the trial
|In the Member State concerned years
|In the Member State concerned months
|In the Member State concerned days
|In all countries concerned by the trial years
|In all countries concerned by the trial months
|In all countries concerned by the trial days