The Efficacy and Mechanism Evaluation of Treating Idiopathic Pulmonary Fibrosis with the Addition of Co-trimoxazole (EME-TIPAC)

INTERVENTION: Trade Name: Cotrimoxazole Product Name: Cotrimoxazole Product Code: NA Pharmaceutical Form: Tablet INN or Proposed INN: trimethoprim CAS Number: 738‐70‐5 Current Sponsor code: none Other descriptive name: none Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 80‐ INN or Proposed INN: sulphamethoxazole CAS Number: 723‐46‐6 Current Sponsor code: none Other descriptive name: none Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 400‐ Pharmaceutical form of the placebo: Tablet Route of administration of the placebo: Oral use CONDITION: Idiopathic Pulmonary Fibrosis ; MedDRA version: 18.0 Level: PT Classification code 10021240 Term: Idiopathic pulmonary fibrosis System Organ Class: 10038738 ‐ Respiratory, thoracic and mediastinal disorders Therapeutic area: Diseases [C] ‐ Respiratory Tract Diseases [C08] PRIMARY OUTCOME: Main Objective: 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. Primary end point(s): The time to death (all causes), lung transplant or the first non‐elective hospital admission. Secondary Objective: 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. 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. SECONDARY OUTCOME: 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; 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. 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 representativ