European Trial of Pirfenidone in BOS, A European Multi-center Study

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02262299
• Date of registration: 21/09/2014
• Prospective Registration: Yes
• Primary sponsor: Rigshospitalet, Denmark
• Public title: European Trial of Pirfenidone in BOS, A European Multi-center Study EPOS
• Scientific title: A European Multi-center, Randomised, Double-blind Trial of Pirfenidone in Bronchiolitis-obliterans-syndrome Grade 1-3 in Lung Transplant Recipients
• Date of first enrolment: May 2015
• Target sample size: 90
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02262299
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Triple (Participant, Care Provider, Investigator).
• Phase: Phase 2/Phase 3

Countries of recruitment

Belgium, Denmark, Germany, Netherlands, Norway, Sweden, United Kingdom

Contacts

• Name: Michael Perch, MD
• Affiliation: Rigshospitalet, Denmark

Key inclusion & exclusion criteria

Inclusion Criteria:

- Patients >18 years of age

- Azithromycin therapy for at least 4 weeks prior to study start, with an Azithromycin
dose of minimum 250 mg/day at least 3 times per week as this is considered standard
therapy for bronchiolitis obliterans syndrome.

- Double lung transplantation is required.

- Patients must be at least 6 months after transplantation and must have documented
post-transplant baseline value of FEV1 (mean of the 2 highest values measured at least
3 weeks apart according to ISHLT criteria).

- Patients must have BOS grade 1 to BOS grade 3.

- Patients must have documented progressive disease as demonstrated by all of the
following criteria:

- Patients must have 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 i

- a decline of at least 50 ml in the last two measurements

Exclusion Criteria

- Patients with lung redo transplantation, combined transplantation (including heart and
lung transplantation) or single lung recipients.

- 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 the last 12 months.

- FEV1 decline related to other non BOS causes (eg pneumothorax, bronchial stenosis,
effusion, etc.)

- Patients who have developed BOS grade 3.

- 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.

- Documented acute perivascular rejection higher than grade A1 or findings compatible
with antibody mediated rejection

- Pregnancy or lactation (women of childbearing capacity are required to have a negative
serum pregnancy test before treatment and must agree to maintain highly effective
contraception by practicing abstinence or by using at least two methods of birth
control from the date of consent through the end of the study).

- Renal insufficiency (Creatinine clearance <30 ml/min calculated by the CKD-Epi
formula.

- 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

- Known allergy or hypersensitivity to Pirfenidone

- Ongoing use or expected use of any of the following therapies:

- Strong inhibitors of CYP1A2 (e.g. fluvoxamine or enoxacin)

- Moderate inhibitors of CYP1A2 (e.g. mexiletine, thiabendazole, or phenylpropanolamine
[Note: ciprofloxacin will be allowed only at doses =500 mg BID])

- Previous treatment with Pirfenidone after transplantation

- Patients who have resumed smoking after transplantation



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

CLAD, Bronchiolitis Obliterans

Disorder Related to Lung Transplantation

Intervention(s)

Drug: Pirfenidone

Drug: Placebo

Primary Outcome(s)

To evaluate the effect of Pirfenidone on the change in FEV1 in liters over 6 months in lung transplant recipients with bronchiolitis obliterans syndrome. [Time Frame: 6 months]

Secondary Outcome(s)

- Change in BOS grade [Time Frame: 6 months]

- Change in QoL as assessed by EQ5D [Time Frame: 6 months]

- Change in Forced Vital Capacity (FVC) [Time Frame: 6 months]

- Change in FEV1/FVC ratio [Time Frame: 6 months]

- Death or re-transplantation rates [Time Frame: 6 months]

- Change in functional level as assessed by the 6MWT [Time Frame: 6 months]

- Change in percent predicted diffusion capacity (DLCO) [Time Frame: 6 months]

- Number of patients with treatment failure [Time Frame: 6 months]

- Categorical percentage change in FEV1 [Time Frame: 6 months]

- Hospital admission for any reason [Time Frame: 6 months]

- Change in Total Lung Capacity (TLC) [Time Frame: 6 months]

Secondary ID(s)

RH-HJE-2014-09

Source(s) of Monetary Support

Please refer to primary and secondary sponsors