E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Idiopathic Pulmonary Fibrosis |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10021240 |
E.1.2 | Term | Idiopathic pulmonary fibrosis |
E.1.2 | System Organ Class | 10038738 - Respiratory, thoracic and mediastinal disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Does co-trimoxazole change the life expectancy and/or reduce the chances of being admitted to hospital or having a lung transplant for people with pulmonary fibrosis. |
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E.2.2 | Secondary objectives of the trial |
Does co-trimoxazole change how patients feel about their quality of life or their breathlessness and/or cough, their oxygen levels, breathing tests or blood biomarkers. Fifty patients will undergo a lung camera test (bronchoscopy) to obtain lung fluid samples to find out whether co-trimoxazole changes the numbers or amount of inflammatory cells, biomarkers and bacteria (using traditional and new techniques). The biomarkers will tell us about inflammation, lung damage and scar production. An additional objective is to find out whether the changes in inflammatory cells' biomarkers or bugs relate to the changes in clinical outcomes. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Male or female, aged greater than or equal to 40 years. IPF rarely occurs in individuals less than 40 years. Individuals younger than this more frequently have connective tissue related lung disease which is similar to but different from IPF. 2) A diagnosis of idiopathic pulmonary fibrosis (IPF) based on multi-disciplinary consensus according to the latest international guidelines within 2 years of enrolment into the study. Patients with a diagnosis of more than 2 years duration can be enrolled if they have evidence of progressive disease defined as ≥10% decline in forced vital capacity (FVC) or ≥15% decline in diffusing capacity of carbon monoxide over the preceding 6 or 12 months. 3) Patients may receive oral prednisolone up to a dose of 10 mg per day, anti-oxidant therapy, pirfenidone or other licensed medication for IPF e.g. nintedanib. Patients should be on a stable treatment regimen for at least 6 weeks to ensure baseline values are representative. 4) MRC dyspnoea score of greater than 1. 5) Able to provide informed consent.
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E.4 | Principal exclusion criteria |
1) FVC > 70% predicted. 2) A recognised significant co-existing respiratory disease, defined as a respiratory condition that exhibits a greater clinical effect on respiratory symptoms and disease progression than IPF as determined by the principal investigator. 3) Patients with airways disease defined as forced expiratory volume in 1 second (FEV1)/FVC<60% 4) A self-reported respiratory tract infection within 4 weeks of screening defined as two or more of cough, sputum or breathlessness and requiring antimicrobial therapy. 5) Significant medical, surgical or psychiatric disease that in the opinion of the patient’s attending physician would affect subject safety or influence the study outcome including liver (Serum transaminase > 3 x upper limit of normal (ULN), Bilirubin > 2 x ULN) and renal failure (creatinine clearance <30ml/min). 6) Patients receiving recognised immunosuppressant medication (except prednisolone above) including azathioprine and mycophenolate mofetil. 7) Female subjects must be of non-childbearing potential, defined as follows: postmenopausal females who have had at least 12 months of spontaneous amenorrhea or 6 months of spontaneous amenorrhoea with serum FSH>40mIU/ml or females who have had a hysterectomy or bilateral oophorectomy at least 6 weeks prior to enrolment. 8) Allergy or intolerance to trimethoprim or sulphonamides or their combination. 9) Untreated folate or B12 deficiency. 10) Known glucose-6-phosphate dehydrogenase (G6PD) deficiency or G6PD deficiency measured at screening in males of African, Asian or Mediterranean descent. 11) Receipt of an investigational drug or biological agent within the 4 weeks prior to study entry or 5 times the half-life if longer.
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E.5 End points |
E.5.1 | Primary end point(s) |
The time to death (all causes), lung transplant or the first non-elective hospital admission. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
From randomisation of first patient until 12 months after the last patient is randomised, follow up is at 6 weeks, 3 months, 6 months, 9 months 12 months and then every 6 months. |
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E.5.2 | Secondary end point(s) |
Secondary efficacy outcomes • Time from randomisation to death (all causes) • Time from randomisation to first non-elective hospital admission for any reason • Health related quality of life: (i)the King’s Brief Interstitial Lung Disease (K-BILD) health related quality of life questionnaire; (ii) the MRC Breathlessness Score; (iii) the EQ5D quality adjusted life year’s assessment, (iv) cough score Lung function including assessment by spirometry and total lung diffusing capacity of carbon monoxide (DLCO) Secondary outcome measures for safety • Full blood count • Urea and electrolytes • Liver function • Adverse Events including SAEs Further exploratory and mechanistic outcomes From the stored blood the proposed analyses, which is subject to change depending on the results of the bronchoscopy results. • CRP as a measure of infection/inflammation; • SP-D as a markers of epithelial injury; • MMP-7 as a marker of disease severity; • Neutrophil count
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
From randomisation of first patient until 12 months after the last patient is randomised, follow up is at 6 weeks, 3 months, 6 months, 9 months 12 months and then every 6 months. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 28 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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12 months after the LVLS to enable data cleaning activities to be completed in all sites |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |