Bronchiolitis Obliterans Syndrome (BOS) in patients following lung transplantation. This syndrome occurs due to rejection of the transplanted organ (s). MedDRA version: 20.0 Level: LLT Classification code 10049202 Term: Bronchiolitis obliterans System Organ Class: 100000015490
Conditions
Interventions
Trade Name: Esbriet
Product Name: Pirfenidone
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: PIRFENIDONE
CAS Number: 53179-13-8
Current Sponsor code: PIR
Other descriptive name: 5-Methyl-1-Ph
Sponsors
Clinical Trials Unit, Rigshospitalet
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patients >18 years of age 2. Azithromycin therapy for at least 4 weeks prior to study start, with an Azithromycin dose of minimum 250mg /day at least 3 times per week 3. Double lung transplantation is required; 4. Patients must be at least 6 months after transplantation and must have documented post-transplant, base-line value of FEV1 (mean of the 2 highest values measured at least 3 weeks apart according to ISHLT criteria) 5. Patients must have BOS grade 1 -3 6. Patients must have documented progressive disease as demonstrated by: • At least 3 FEV1 measurements in the last 6 months each at least 3 weeks apart • a total decline of at least 200mL in FEV1 in the last six months • a mean decline of at least 50 mL in the last two measurements Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 70 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: 1. Patients with redo lung transplantation or combined transplantation (including heart and lung transplantation) Or Single lung recipients 2. Patients with any severe comorbidity complicating BOS which might determine the prognosis and functional level of the patient (e.g. invasive aspergillosis, active malignant disease within last 12 months (i.e. disease free since at least 12 months)) 3. FEV1 decline related to other non BOS causes (eg pneumothorax, bronchial stenosis, effusion, etc.) 4. Screening ECG shows QTc > 500 ms 5. Patients who on Thorax CT at entry demonstrate new significant findings which are not compatible with BOS like interstitial fibrosis, consolidation, appearances suggesting restrictive Allograft Syndrome (RAS) and acute pulmonary infection as cause of decline in lung function 6. Documented acute perivascular rejection higher than grade A1 or findings compatible with antibody mediated rejection at the last trans-bronchial biopsy performed. 7. Pregnancy or lactation. 8. Renal insufficiency (Creatinine clearance 3 × ULN • Subjects with severe liver impairment (Child Pugh C) 10. Known allergy or hypersensitivity to Pirfenidone 11. Ongoing use or expected use of any of the following therapies: • Strong inhibitors of CYP1A2 (fluvoxamine or enoxacin) • Moderate inhibitors of CYP1A2 (mexiletine, thiabendazole, oral contraceptives or phenylpropanolamine [Note: ciprofloxacin will be allowed only at doses =500 mg BID]) • Moderate inducers (montelukast, phenytoin) • Cimetidine • Previous treatment with Pirfenidone after transplantation 12. Patients who have resumed smoking after transplantation 13. Initiation of a new bronchodilator therapy or treatment with Montelukast within 4 weeks prior to randomization
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the effect of Pirfenidone on the change in FEV1 over 6 months in lung transplant recipients with bronchiolitis obliterans syndrome, who are treated with Azithromycin.;Secondary Objective: • Categorical percentage change in FEV1 [Categorical percentage change in FEV1 = 10 % (increase or decrease) relative to FEV1 (ml) at baseline] • Change of FVC in liters • Change in TLC in liters • FEV1/FVC ratio change • Number of patients with treatment failure • Change in BOS grade • Change in percent predicted DLco. • Change in functional level as assessed by the 6MWT • Hospital admission for any reason • Death or re-transplantation rates • Change in EQ5D scale ;Primary end point(s): The primary endpoint of the study is the change in FEV1 (ml) from baseline to 6 months.;Timepoint(s) of evaluation of this end point: This endpoint will be evaluated at the end of the study (the 6 month visit for each patient). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Categorical percentage change in FEV1 [Categorical percentage change in FEV1 = 10 % (increase or decrease) relative to FEV1 (ml) at baseline] • Change of FVC in liters • Change in TLC in liters • FEV1/FVC ratio change • Number of patients with treatment failure • Change in BOS grade • Change in percent predicted DLco. • Change in functional level as assessed by the 6MWT • Hospital admission for any reason • Death or re-transplantation rates • Change in EQ5D scale ;Timepoint(s) of evaluation of this end point: All secondary endpoints will be evaluated at the end of the study (the 6 month visit for each patient). | — |
Countries
Belgium, Denmark, Germany, Netherlands, Sweden, United Kingdom
Contacts
Public ContactDr. Michael Perch
Rigshopitalet
Outcome results
None listed