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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02262299
Recruitment Status : Completed
First Posted : October 13, 2014
Last Update Posted : January 18, 2020
Sponsor:
Information provided by (Responsible Party):
Michael Perch, Rigshospitalet, Denmark

Brief Summary:

A European multi-centre, randomised, double-blind placebo-controlled trial of Pirfenidone in bronchiolitis-obliterans-syndrome grade 1-3 in lung transplant recipients.

Randomized double blinded, placebo controlled study. Eligible patients are to be randomized in a 1:1 ratio to receive either Pirfenidone 2403 mg/d or the matching placebo treatment for 6 months.

Primary objective To evaluate the effect of Pirfenidone on the change in FEV1 in liters over 6 months in lung transplant recipients with bronchiolitis obliterans syndrome.


Condition or disease Intervention/treatment Phase
Disorder Related to Lung Transplantation CLAD, Bronchiolitis Obliterans Drug: Pirfenidone Drug: Placebo Phase 2 Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 90 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: A European Multi-center, Randomised, Double-blind Trial of Pirfenidone in Bronchiolitis-obliterans-syndrome Grade 1-3 in Lung Transplant Recipients
Actual Study Start Date : May 2015
Actual Primary Completion Date : December 2019
Actual Study Completion Date : December 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Pirfenidone

Arm Intervention/treatment
Placebo Comparator: Placebo
Receive placebo tablets
Drug: Placebo
Recieve tablets with placebo

Active Comparator: Pirfenidone
Upon enrollment, subjects will be randomized to either the treatment group (Pirfenidone) or to the placebo group (1:1 ratio). The trial medication will be administered as 267-mg oral capsules and titrated to a maintenance dose of 2403 mg/d (3 capsules TID, for a total of 9 capsules/day).
Drug: Pirfenidone
Receive tablets with pirfenidone
Other Name: Esbriet




Primary Outcome Measures :
  1. 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 Measures :
  1. - Categorical percentage change in FEV1 [ Time Frame: 6 months ]
  2. - Change in Forced Vital Capacity (FVC) [ Time Frame: 6 months ]
  3. - Change in Total Lung Capacity (TLC) [ Time Frame: 6 months ]
  4. - Change in FEV1/FVC ratio [ Time Frame: 6 months ]
  5. - Number of patients with treatment failure [ Time Frame: 6 months ]
  6. - Change in BOS grade [ Time Frame: 6 months ]
  7. - Change in percent predicted diffusion capacity (DLCO) [ Time Frame: 6 months ]
  8. - Change in functional level as assessed by the 6MWT [ Time Frame: 6 months ]
  9. - Hospital admission for any reason [ Time Frame: 6 months ]
  10. - Death or re-transplantation rates [ Time Frame: 6 months ]
  11. - Change in QoL as assessed by EQ5D [ Time Frame: 6 months ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02262299


Locations
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Belgium
University Hospital Gasthuisberg, Katholike Universiteit Leuven
Leuven, Belgium, 300
Denmark
Rigshospitalet, Copenhagen University Hospital
Copenhagen, Denmark, 2100
Germany
University Hospital Essen, Department of Pneumonology
Essen, Germany, 45239
Medizinische Hochschule Hannover, Klinik für Pneumonologie
Hannover, Germany, 30625
Klinikum Grosshadern, Division of Pulmonary Diseases
Munich, Germany, 81377
Netherlands
Groningen University Medical Center, Lung Transplant Team
Groningen, Netherlands, 9700
Norway
Rikshospitalet, National University Hospital
Oslo, Norway, 0424
Sweden
Sahlgrenska University Hospital, Department of respiratory diseases
Gothenburg, Sweden, 41345
United Kingdom
Freeman Hospital
Newcastle, United Kingdom, NE7 7DN
Sponsors and Collaborators
Rigshospitalet, Denmark
Investigators
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Principal Investigator: Michael Perch, MD Rigshospitalet, Denmark
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Responsible Party: Michael Perch, Medical Director Danish National Lung Transplant Program, Rigshospitalet, Denmark
ClinicalTrials.gov Identifier: NCT02262299    
Other Study ID Numbers: RH-HJE-2014-09
First Posted: October 13, 2014    Key Record Dates
Last Update Posted: January 18, 2020
Last Verified: January 2020
Additional relevant MeSH terms:
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Bronchiolitis
Bronchiolitis Obliterans
Bronchitis
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Tract Infections
Pirfenidone
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Anti-Inflammatory Agents
Antirheumatic Agents
Antineoplastic Agents