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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register.
Register: EUCTR
Last refreshed on: 2 October 2017
Main ID:  EUCTR2014-002022-12-BE
Date of registration: 15/10/2014
Prospective Registration: Yes
Primary sponsor: Clinical Trials Unit, Rigshospitalet
Public title: European Trial of Pirfenidone in BOS (EPOS).
Scientific title: A European multi-centre, randomised, double-blind trial of pirfenidone in bronchiolitis-obliterans-syndrome grade 1-3 in lung transplant recipients. - EPOS Trial
Date of first enrolment: 10/03/2015
Target sample size: 80
Recruitment status: Authorised-recruitment may be ongoing or finished
URL:  https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-002022-12
Study type:  Interventional clinical trial of medicinal product
Study design:  Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2  
Phase:  Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no
Countries of recruitment
Belgium Denmark Germany Netherlands Sweden United Kingdom
Contacts
Name: Dr. Michael Perch   
Address:  Blegdamsvej 9 2100 Copenhagen Denmark
Telephone: 004535459702
Email: Michael.Perch@regionh.dk
Affiliation:  Rigshopitalet
Name: Dr. Michael Perch   
Address:  Blegdamsvej 9 2100 Copenhagen Denmark
Telephone: 004535459702
Email: Michael.Perch@regionh.dk
Affiliation:  Rigshopitalet
Key inclusion & exclusion 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:
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 <30 ml/min calculated by the CKD-Epi formula).
9. Any of the following liver test criteria above the specified limit:
• Total bilirubin above the upper limit of the normal range (ULN), except in patients with predominantly unconjugated hyperbilirubinemia (e.g., Gilbert’s syndrome)
• Aspartate or alanine aminotransferase (AST or ALT) >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


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes
Health Condition(s) or Problem(s) studied
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
Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]
Intervention(s)

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-Phenyl-2-1-(H)-Pyridone
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 267-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Primary Outcome(s)
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.
Primary end point(s): The primary endpoint of the study is the change in FEV1 (ml) from baseline to 6 months.
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
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 Outcome(s)
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).
Secondary ID(s)
2014-002022-12-SE
EPOS-CT-001
Source(s) of Monetary Support
F. Hoffmann La Roche Ltd
Secondary Sponsor(s)
Ethics review
Results
Results available:
Date Posted:
Date Completed:
URL:
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