CHORUS: a multi-centre double-blind randomised placebo-controlled group-sequential superiority trial to assess the effectiveness and cost-effectiveness of oral Corticosteroids in patients witH fibrOtic hypeRsensitivity pneUmonitiS
Fibrotic hypersensitivity pneumonitis
Participants will be randomised into the trial by a delegated member of the site team using an online randomisation service. Trial participants will be randomised on a 1:1 ratio to receive either 26 weeks prednisolone or 26 weeks placebo. For blinding purposes, the active drug will be over-encapsulated. Placebo capsules will be manufactured to match in appearance but will not contain any active ingredients. Participants will start on a dose of 40 mg (or matched placebo capsules) which will be gradually reduced over 12 weeks to a 10 mg maintenance dose which will be taken for 14 weeks. This will be followed by a 9-week IMP weaning period.
1. Age ≥18 years 2. ILD multi-disciplinary diagnosis of FHP within the last 6 months 3. % predicted FVC ≥40% at baseline (as per GLI equation) 4. % predicted DLCO ≥25% at baseline 5. FEV1/FVC ratio ≥0.7 at baseline 6. >10% fibrosis on CT taken as standard of care for the MDT diagnosis 7. Able to provide informed consent 8. People of child-bearing potential must be willing to: 8.1. Take a pregnancy test at baseline, before randomisation 8.2. Use of a highly effective method of contraception for the duration of the trial (35 weeks) 8.3. Inform the research clinical team if pregnancy occurs during trial participation
1. Previous or current therapy with prednisolone or other immunosuppressive agent for FHP 2. Active infection (use of antibiotics must be completed 2 weeks prior to the baseline visit. Prophylactic antibiotics are allowed) 3. Emphysema>fibrosis on CT scan 4. BMI>44 kg/m2 5. Currently enrolled in another investigational drug trial 6. Non-respiratory conditions requiring use of immunosuppressive therapy (including prednisolone) 7. Any condition that might be significantly exacerbated by the administration of prednisolone, including but not limited to: Cushing’s and Conn’s Syndromes, Addison’s disease, poorly controlled/difficult to control diabetes 8. Patients with underlying liver cirrhosis (Child Pugh, B, or C hepatic impairment). 9. Stage 4/5 chronic kidney disease (eGFR <30 ml/min/1.73 m2) 10. Patients with unstable cardiac disease or a significant disease or condition other than the ILD under trial, which in the opinion of the investigator, may put the patient at risk because of participation, interfere with trial procedures, or cause concern regarding the patient’s ability to participate in the trial 11. Use of potent inducers of prednisolone including phenytoin, rifabutin, carbamazepine, ketoconazole, rifamycins. Please refer to the Summary of Product Characteristics 12. Patients with ocular herpes simplex 13. Known allergy to prednisolone or its excipients including lactose anhydrous or capsule ingredients hydroxypropylmethylcellulose, water, dye – copper complex of chlorophyllins E141ii 14. Pregnant, breastfeeding, or planning to conceive in the next 35 weeks