PMID- 30233802
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220321
IS  - 2052-4439 (Print)
IS  - 2052-4439 (Electronic)
IS  - 2052-4439 (Linking)
VI  - 5
IP  - 1
DP  - 2018
TI  - Pirfenidone in patients with unclassifiable progressive fibrosing interstitial 
      lung disease: design of a double-blind, randomised, placebo-controlled phase II 
      trial.
PG  - e000289
LID - 10.1136/bmjresp-2018-000289 [doi]
LID - e000289
AB  - INTRODUCTION: Despite extensive multidisciplinary team (MDT) assessment, some 
      patients have interstitial lung disease (ILD) that is considered unclassifiable 
      (uILD), for which there are currently no approved treatments. This study will 
      assess the efficacy and safety of the antifibrotic pirfenidone in treating uILD. 
      METHODS AND ANALYSIS: This double-blind, randomised, placebo-controlled phase II 
      trial is enrolling adults with fibrosing ILD, including uILD that fulfils 
      proposed research criteria for interstitial pneumonia with autoimmune features 
      (IPAF), that cannot be classified with moderate or high confidence to any 
      category of ILD following MDT discussion. Study participants must have >10% 
      fibrosis on high-resolution CT scan within the previous 12 months, forced vital 
      capacity (FVC) >/=45% and diffusing capacity of the lung for carbon monoxide >/=30% 
      of predicted values. Study participants will be randomised to receive 801 mg 
      pirfenidone or placebo three times daily for 24 weeks. The efficacy of 
      pirfenidone vs placebo will be assessed by daily measurement of FVC using a 
      handheld spirometer over the treatment period. Other functional parameters, 
      patient-reported outcomes, samples for biomarker analysis and safety endpoints 
      will be collected. Additionally, the study will assess the efficacy and safety of 
      pirfenidone with and without concomitant mycophenolate mofetil treatment and in 
      study participants with or without IPAF. ETHICS AND DISSEMINATION: This trial is 
      being conducted in accordance with the International Conference on Harmonisation 
      E6 guideline for Good Clinical Practice, Declaration of Helsinki and local laws 
      for countries in which the research is conducted. TRIAL REGISTRATION NUMBER: 
      NCT03099187.
FAU - Maher, Toby M
AU  - Maher TM
AUID- ORCID: 0000-0001-7192-9149
AD  - NIHR Respiratory Clinical Research Facility, Royal Brompton Hospital, London, UK.
AD  - Fibrosis Research Group, National Heart and Lung Institute, Imperial College 
      London, London, UK.
FAU - Corte, Tamera J
AU  - Corte TJ
AD  - Department of Respiratory Medicine, Royal Prince Alfred Hospital, Camperdown, New 
      South Wales, Australia.
AD  - Medical School, University of Sydney, Camperdown, New South Wales, Australia.
FAU - Fischer, Aryeh
AU  - Fischer A
AD  - Department of Medicine, University of Colorado School of Medicine, Aurora, 
      Colorado, USA.
FAU - Kreuter, Michael
AU  - Kreuter M
AD  - Center for Interstitial and Rare Lung Diseases and Department of Pulmonology and 
      Critical Care Medicine, Thoraxklinik, Member of the German Center for Lung 
      Research, University of Heidelberg, Heidelberg, Germany.
FAU - Lederer, David J
AU  - Lederer DJ
AD  - Divison of Pulmonary, Allergy, and Critical Care Medicine, Columbia University 
      Medical Center, New York City, New York, USA.
FAU - Molina-Molina, Maria
AU  - Molina-Molina M
AD  - Institut d'Investigacio Biomedica de Bellvitge (IDIBELL), University Hospital of 
      Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain.
AD  - Centro de Investigacion Biomedica en Red Enfermedades Respiratorias (CIBERES), 
      Madrid, Spain.
FAU - Axmann, Judit
AU  - Axmann J
AD  - F. Hoffmann-La Roche, Ltd., Basel, Switzerland.
FAU - Kirchgaessler, Klaus-Uwe
AU  - Kirchgaessler KU
AD  - F. Hoffmann-La Roche, Ltd., Basel, Switzerland.
FAU - Cottin, Vincent
AU  - Cottin V
AD  - National Reference Center for Rare Pulmonary Diseases, Louis Pradel Hospital, 
      Lyon, France.
AD  - Hospices Civils de Lyon, Universite Claude Bernard Lyon 1, Lyon, France.
LA  - eng
SI  - ClinicalTrials.gov/NCT03099187
GR  - CS-2013-13-017/DH_/Department of Health/United Kingdom
PT  - Journal Article
DEP - 20180904
PL  - England
TA  - BMJ Open Respir Res
JT  - BMJ open respiratory research
JID - 101638061
PMC - PMC6135451
OTO - NOTNLM
OT  - antifibrotic
OT  - interstitial pneumonia with autoimmune features
OT  - pirfenidone
OT  - unclassifiable interstitial lung disease
COIS- Competing interests: TMM has received industry-academic research funding from 
      GlaxoSmithKline R&D and UCB, has served on a clinical trial advisory board for 
      GlaxoSmithKline R&D, has received stock options from Apellis and has received 
      consultancy or speaker fees from AstraZeneca, Bayer, Biogen Idec, Boehringer 
      Ingelheim, Cipla, GlaxoSmithKline R&D, ProMetic, Roche, Sanumed and UCB. TJC has 
      received unrestricted educational grants, travel assistance and speaker fees from 
      and served on an advisory board for Boehringer Ingelheim, has received 
      unrestricted educational grants and speaker fees from and served on an advisory 
      board for Roche, has received unrestricted educational grants from Actelion Ltd., 
      Bayer, BMS and Sanofi and has served on an advisory board for AstraZeneca. AF 
      serves as a consultant and steering committee member for Boehringer Ingelheim and 
      Roche. MK, or his institution, has received unrestricted educational grants, 
      speaker fees and research grants from Boehringer Ingelheim and Roche and has 
      served on advisory boards for Boehringer Ingelheim and Roche. DJL is a steering 
      committee member for this study and has received consulting fees from and has 
      served on advisory boards for Genentech-Roche and Veracyte, has served on 
      advisory boards for Boehringer Ingelheim, has served on an adjudication committee 
      for Degge Group, has received lecture fees and fees for generation of educational 
      content from and served on a steering committee for the France Foundation and has 
      received consulting fees from FibroGen, Global Blood Therapeutics, ImmuneWorks, 
      Patara Pharmaceuticals, Philips Respironics and Sanofi Genzyme. DJL's 
      institution, Columbia University, has received funding for clinical trials in IPF 
      from Boehringer Ingelheim, FibroGen and Global Blood Therapeutics and has 
      received consulting fees from the Pulmonary Fibrosis Foundation. MM-M, or her 
      institution, has received grants from AstraZeneca, Boehringer Ingelheim, BRN, 
      Chiesi, GlaxoSmithKline, InterMune and Roche. JA is an employee of F. Hoffmann-La 
      Roche, Ltd. K-UK is an employee and shareholder of F. Hoffmann-La Roche, Ltd. VC 
      receives consultancy and lecture fees and support for travel to medical meetings 
      from Actelion and Roche, receives consultancy and lecture fees, support for 
      travel to medical meetings and fees for development of educational presentations 
      from Boehringer Ingelheim, receives consultancy and lecture fees from Novartis 
      and Sanofi, receives consultancy fees from Bayer, Galapagos, GlaxoSmithKline and 
      MSD, is a member of an adjudication committee for Gilead, is a chair of the DSMB 
      for Promedior, is a member of the DSMB for Celgene and receives grants to his 
      institution from Boehringer Ingelheim and Roche.
EDAT- 2018/09/21 06:00
MHDA- 2018/09/21 06:01
PMCR- 2018/09/04
CRDT- 2018/09/21 06:00
PHST- 2018/05/09 00:00 [received]
PHST- 2018/07/05 00:00 [revised]
PHST- 2018/07/13 00:00 [accepted]
PHST- 2018/09/21 06:00 [entrez]
PHST- 2018/09/21 06:00 [pubmed]
PHST- 2018/09/21 06:01 [medline]
PHST- 2018/09/04 00:00 [pmc-release]
AID - bmjresp-2018-000289 [pii]
AID - 10.1136/bmjresp-2018-000289 [doi]
PST - epublish
SO  - BMJ Open Respir Res. 2018 Sep 4;5(1):e000289. doi: 10.1136/bmjresp-2018-000289. 
      eCollection 2018.