Clinical trial NCT02999178: Efficacy and Safety of Nintedanib in Patients With Progressive Fibrosing Interstitial Lung Disease (PF-ILD)
Official title: A Double Blind, Randomized, Placebo-controlled Trial Evaluating the Efficacy and Safety of Nintedanib Over 52 Weeks in Patients With Progressive Fibrosing Interstitial Lung Disease (PF-ILD)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Lung Diseases, Interstitial
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2016-12-21
Enrollment: 663
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The aim of the current study is to investigate the efficacy and safety of nintedanib over 52 weeks in patients with Progressive Fibrosing Interstitial Lung Disease (PF-ILD) defined as patients who present with features of diffuse fibrosing lung disease of \>10% extent on high-resolution computed tomography (HRCT) and whose lung function and respiratory symptoms or chest imaging have worsened despite treatment with unapproved medications used in clinical practice to treat ILD. There is currently no efficacious treatment available for PF-ILD. Based on its efficacy and safety in Idiopathic Pulmonary Fibrosis (IPF), it is anticipated that Nintedanib will be a new treatment option for patients with PF-ILD.


Eligibility criteria: Inclusion criteria:

* Written Informed Consent consistent with International Conference on Harmonisation Harmonised Tripartite Guideline for Good Clinical Practice (ICH-GCP) and local laws signed prior to entry into the study (and prior to any study procedure including shipment of High Resolution Computer Tomography (HRCT) to reviewer).
* Male or female patients aged \>= 18 years at Visit 1.
* Patients with physician diagnosed Interstitial Lung Disease (ILD) who fulfil at least one of the following criteria for Progressive Fibrosing Interstitial Lung Disease (PF-ILD) within 24 months of screening visit (Visit 1) despite treatment with unapproved medications used in clinical practice to treat ILD, as assessed by the investigator (refer to Exclusion Criteria):

  * Clinically significant decline in Forced Vital Capacity (FVC) % pred based on a relative decline of \>=10%
  * Marginal decline in FVC % pred based on a relative decline of .\>=5-\<10% combined with worsening of respiratory symptoms
  * Marginal decline in FVC % pred based on a relative decline of \>=5-\<10% combined with increasing extent of fibrotic changes on chest imaging
  * Worsening of respiratory symptoms as well as increasing extent of fibrotic changes on chest imaging \[Note: Changes attributable to comorbidities e.g. infection, heart failure must be excluded. Unapproved medications used in the clinical practice to treat ILD include but are not limited to corticosteroid, azathioprine, mycophenolate mofetil (MMF), n-acetylcysteine (NAC), rituximab, cyclophosphamide, cyclosporine, tacrolimus\].
* Fibrosing lung disease on HRCT, defined as reticular abnormality with traction bronchiectasis with or without honeycombing, with disease extent of \>10%, performed within 12 months of Visit 1 as confirmed by central readers.
* For patients with underlying Connective Tissue Disease (CTD): stable CTD as defined by no initiation of new therapy or withdrawal of therapy for CTD within 6 weeks prior to Visit 1.
* Carbon Monoxide Diffusion Capacity (DLCO) corrected for Haemoglobin (Hb) \[visit 1\] ≥ 30% and \<80% predicted of normal at Visit 2
* FVC \>= 45% predicted at Visit 2

Exclusion criteria:

* Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) \> 1.5 x Upper Limit of Normal (ULN) at Visit 1
* Bilirubin \> 1.5 x ULN at Visit 1
* Creatinine clearance \<30 mL/min calculated by Cockcroft-Gault formula at Visit 1 \[Note: Laboratory parameters from Visit 1 have to satisfy the laboratory threshold values as shown above. Visit 2 laboratory results will be available only after randomization. In case at Visit 2 the results do no longer satisfy the entry criteria, the Investigator has to decide whether it is justified that the patient remains on study drug. The justification for decision needs to be documented. Laboratory parameters that are found to be abnormal at Visit 1 are allowed to be re-tested (once) if it is thought to be a measurement error (i.e. there was no abnormal result of this test in the recent history of the patient and there is no related clinical sign) or the result of a temporary and reversible medical condition, once that condition is resolved\].
* Patients with underlying chronic liver disease (Child Pugh A, B or C hepatic impairment).
* Previous treatment with nintedanib or pirfenidone.
* Other investigational therapy received within 1 month or 6 half-lives (whichever was greater) prior to screening visit (Visit 1).
* Use of any of the following medications for the treatment of Interstitial Lung Disease (ILD): azathioprine (AZA), cyclosporine, MMF, tacrolimus, oral corticosteroids (OCS) \>20mg/day and the combination of OCS+AZA+NAC within 4 weeks of Visit 2, cyclophosphamide within 8 weeks of Visit 2, rituximab within 6 months of Visit 2.

Note: Patients whose Rheumatoid Arthritis (RA)/Connective Tissue Disease (CTD) is managed by these medications should not be considered for participation in the current study unless change in RA/CTD medication is medically indicated (see Inclusion Criteria)

* Diagnosis of Idiopathic Pulmonary Fibrosis (IPF) based on American Thoracic Society (ATS)/ European Respiratory Society (ERS)/Japanese Respiratory Society (JRS)/Latin American Thoracic Association (ALAT) 2011 Guidelines.
* Significant Pulmonary Arterial Hypertension (PAH) defined by any of the following:

  * Previous clinical or echocardiographic evidence of significant right heart failure
  * History of right heart catheterization showing a cardiac index \<= 2 l/min/m²
  * PAH requiring parenteral therapy with epoprostenol/treprostinil
  * Primary obstructive airway physiology (pre-bronchodilator FEV1/FVC \< 0.7 at Visit 1).
  * In the opinion of the Investigator, other clinically significant pulmonary abnormalities.
* Major extrapulmonary physiological restriction (e.g. chest wall abnormality, large pleural effusion)
* Cardiovascular diseases, any of the following:

  * Severe hypertension, uncontrolled under treatment (≥160/100 mmHg), within 6 month of Visit 1
  * Myocardial infarction within 6 months of Visit 1
  * Unstable cardiac angina within 6 months of Visit 1
* Bleeding risk, any of the following:

  * Known genetic predisposition to bleeding.
  * Patients who require

    * Fibrinolysis, full-dose therapeutic anticoagulation (e.g. vitamin K antagonists, direct thrombin inhibitors, heparin, hirudin)
    * High dose antiplatelet therapy. \[Note: Prophylactic low dose heparin or heparin flush as needed for maintenance of an indwelling intravenous device (e.g. enoxaparin 4000 I.U. s.c. per day), as well as prophylactic use of antiplatelet therapy (e.g. acetyl salicylic acid up to 325 mg/day, or clopidogrel at 75 mg/day, or equivalent doses of other antiplatelet therapy) are not prohibited\].
  * History of haemorrhagic central nervous system (CNS) event within 12 months of Visit 1.
  * Any of the following within 3 months of Visit 1:

    * Haemoptysis or haematuria
    * Active gastro-intestinal (GI) bleeding or GI - ulcers
    * Major injury or surgery (Investigators judgment).
  * Coagulation parameters: International normalized ratio (INR) \>2, prolongation of prothrombin time (PT) and activated partial thromboplastin time (aPTT) by \>1.5 x ULN at Visit 1.
* History of thrombotic event (including stroke and transient ischemic attack) within 12 months of Visit 1.
* Known hypersensitivity to the trial medication or its components (i.e. soya lecithin)
* Patients with peanut allergy.
* Other disease that may interfere with testing procedures or in the judgment of the Investigator may interfere with trial participation or may put the patient at risk when participating in this trial.
* Life expectancy for disease other than ILD \< 2.5 years (Investigator assessment).
* Planned major surgical procedures.
* Women who are pregnant, nursing, or who plan to become pregnant while in the trial.
* Women of childbearing potential\* not willing or able to use highly effective methods of birth control per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly as well as one barrier method for 28 days prior to and 3 months after nintedanib administration. A list of contraception methods meeting these criteria is provided in the patient information.
* In the opinion of the Investigator, active alcohol or drug abuse.
* Patients not able to understand or follow trial procedures including completion of self-administered questionnaires without help. \*A woman is considered of childbearing potential, i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy.

Primary outcomes:
measure: Annual Rate of Decline in Forced Vital Capacity - Overall Population
timeFrame: Baseline, 2, 4, 6, 12, 24, 36, 52 weeks after first drug intake (planned post-baseline visits)
measure: Annual Rate of Decline in Forced Vital Capacity - Participants With HRCT Fibrotic Pattern=UIP-like Fibrotic Pattern Only
timeFrame: Baseline, 2, 4, 6, 12, 24, 36, 52 weeks after first drug intake (planned post-baseline visits)
Secondary outcomes:
measure: Absolute Change From Baseline in King's Brief Interstitial Lung Disease Questionnaire (K-BILD) Total Score at Week 52 - Overall Population
timeFrame: Baseline, 12, 24, 36, 52 weeks after first drug intake (planned post-baseline visits)
measure: Absolute Change From Baseline in King's Brief Interstitial Lung Disease (K-BILD) Questionnaire Total Score at Week 52 - Participants With HRCT Fibrotic Pattern=UIP-like Fibrotic Pattern Only
timeFrame: Baseline, 12, 24, 36, 52 weeks after first drug intake (planned post-baseline visits)
measure: Time to First Acute Interstitial Lung Disease (ILD) Exacerbation or Death Over 52 Weeks - Overall Population
timeFrame: From first drug intake until date of first acute ILD exacerbation or date of death or last contact date, up to 372 days
measure: Time to First Acute Interstitial Lung Disease (ILD) Exacerbation or Death Over 52 Weeks - Participants With HRCT Fibrotic Pattern=UIP-like Fibrotic Pattern Only
timeFrame: From first drug intake until date of first acute ILD exacerbation or date of death or last contact date, up to 372 days
measure: Time to Death Over 52 Weeks - Overall Population
timeFrame: From first drug intake until date of death or last contact date, up to 372 days
measure: Time to Death Over 52 Weeks - Participants With HRCT Fibrotic Pattern=UIP-like Fibrotic Pattern Only
timeFrame: From first drug intake until date of death or last contact date, up to 372 days
measure: Time to Death Due to Respiratory Cause Over 52 Weeks - Overall Population
timeFrame: From date of first trial drug intake up to date of death from respiratory causes or last contact date, up to 372 days
measure: Time to Death Due to Respiratory Cause Over 52 Weeks - Participants With HRCT Fibrotic Pattern=UIP-like Fibrotic Pattern Only
timeFrame: From date of first trial drug intake up to date of death from respiratory causes or last contact date, up to 372 days
measure: Time to Progression or Death Over 52 Weeks - Overall Population
timeFrame: From first drug intake until date of progression or date of death or last contact date, up to 372 days
measure: Time to Progression or Death Over 52 Weeks - Participants With HRCT Fibrotic Pattern=UIP-like Fibrotic Pattern Only
timeFrame: From first drug intake until date of progression or date of death or last contact date, up to 372 days
measure: Percentage of Participants With a Relative Decline From Baseline in FVC Percent Predicted of More Than 10 Percent at Week 52 - Overall Population
timeFrame: Baseline and up to 52 weeks after first drug intake
measure: Percentage of Participants With a Relative Decline From Baseline in FVC Percent Predicted of More Than 10 Percent at Week 52 - Participants With HRCT Fibrotic Pattern=UIP-like Fibrotic Pattern Only
timeFrame: Baseline and up to 52 weeks after first drug intake
measure: Percentage of Participants With a Relative Decline From Baseline in FVC Percent Predicted of More Than 5 Percent at Week 52 - Overall Population
timeFrame: Baseline and up to 52 weeks after first drug intake
measure: Percentage of Participants With a Relative Decline From Baseline in FVC Percent Predicted of More Than 5 Percent at Week 52 - Participants With HRCT Fibrotic Pattern=UIP-like Fibrotic Pattern Only
timeFrame: Baseline and up to 52 weeks after first drug intake
measure: Absolute Change From Baseline in Living With Pulmonary Fibrosis (L-PF) Symptoms Dyspnea Domain Score at Week 52 - Overall Population
timeFrame: Baseline, 12, 24, 36, 52 weeks after first drug intake (planned post-baseline visits)
measure: Absolute Change From Baseline in L-PF Symptoms Dyspnea Domain Score at Week 52 - Participants With HRCT Fibrotic Pattern=UIP-like Fibrotic Pattern Only
timeFrame: Baseline, 12, 24, 36, 52 weeks after first drug intake (planned post-baseline visits)
measure: Absolute Change From Baseline in L-PF Symptoms Cough Domain Score at Week 52 - Overall Population
timeFrame: Baseline, 12, 24, 36, 52 weeks after first drug intake (planned post-baseline visits)
measure: Absolute Change From Baseline in Living With Pulmonary Fibrosis (L-PF) Symptoms Cough Domain Score at Week 52 - Participants With HRCT Fibrotic Pattern=UIP-like Fibrotic Pattern Only
timeFrame: Baseline, 12, 24, 36, 52 weeks after first drug intake (planned post-baseline visits)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Los Angeles
country: United States
facility: University of California Los Angeles
state: California
city: Sacramento
country: United States
facility: University of California Davis
state: California
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Denver
country: United States
facility: National Jewish Health
state: Colorado
city: Danbury
country: United States
facility: Pulmonary and Sleep Specialists
state: Connecticut
city: New Haven
country: United States
facility: Yale University School of Medicine
state: Connecticut
city: Brandon
country: United States
facility: Pulmonary and Sleep of Tampa Bay
state: Florida
city: Jacksonville
country: United States
facility: University of Florida College of Medicine
state: Florida
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Maywood
country: United States
facility: Loyola University Medical Center
state: Illinois
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Lexington
country: United States
facility: University of Kentucky Medical Center
state: Kentucky
city: Baltimore
country: United States
facility: University of Maryland School of Medicine
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
city: Towson
country: United States
facility: Pulmonary and Critical Care Associates of Baltimore
state: Maryland
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: Pulmonary and Critical Care Medicine
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Grand Rapids
country: United States
facility: Spectrum Health
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota Masonic Cancer Center
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic, Rochester
state: Minnesota
city: Chesterfield
country: United States
facility: The Lung Research Center, LLC
state: Missouri
city: Omaha
country: United States
facility: Creighton University
state: Nebraska
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center
state: New Hampshire
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: New York
country: United States
facility: Columbia University Medical Center-New York Presbyterian Hospital
state: New York
city: New York
country: United States
facility: NewYork-Presbyterian/Weill Cornell Medical Center
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Winston-Salem
country: United States
facility: Southeastern Research Center
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University Wexner Medical Center
state: Ohio
city: Portland
country: United States
facility: The Oregon Clinic
state: Oregon
city: Portland
country: United States
facility: The Oregon Clinic
state: Oregon
city: Hershey
country: United States
facility: Penn State Milton S. Hershey Medical Center
state: Pennsylvania
city: Oaks
country: United States
facility: Temple University Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Columbia
country: United States
facility: University of South Carolina
state: South Carolina
city: Dallas
country: United States
facility: Baylor University Medical Center
state: Texas
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Fort Worth
country: United States
facility: Texas Pul & Crit Care Conslt
state: Texas
city: Houston
country: United States
facility: Houston Methodist Hospital
state: Texas
city: San Antonio
country: United States
facility: Diagnostics Research Group
state: Texas
city: San Antonio
country: United States
facility: Medical Arts and Research Center (MARC)
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah Health Sciences Center
state: Utah
city: Falls Church
country: United States
facility: Inova Fairfax Medical Campus
state: Virginia
city: Richmond
country: United States
facility: Pulmonary Associates of Richmond, Inc.
state: Virginia
city: Alberdi Sur
country: Argentina
facility: Centro Dr. Lazaro Langer S.R.L
city: C.a.b.a
country: Argentina
facility: Centro de Investigaciones Metabólicas (CINME)
city: Ciudad Autónoma de Bs As
country: Argentina
facility: Sanatorio Güemes
city: Florida
country: Argentina
facility: CEMER-Centro Medico De Enfermedades Respiratorias
city: Mendoza
country: Argentina
facility: INSARES
city: Rosario
country: Argentina
facility: Instituto Médico de la Fundación Estudios Clínicos
city: Angleur
country: Belgium
facility: Centre Hospitalier Universitaire de Liège
city: Bruxelles
country: Belgium
facility: ULB Hopital Erasme
city: Leuven
country: Belgium
facility: UZ Leuven
city: Yvoir
country: Belgium
facility: Yvoir - UNIV UCL de Mont-Godinne
city: Winnipeg
country: Canada
facility: Concordia Hospital
state: Manitoba
city: Hamilton
country: Canada
facility: St. Joseph's Healthcare Hamilton
state: Ontario
city: Toronto
country: Canada
facility: Toronto General Hospital
state: Ontario
city: Sherbrooke
country: Canada
facility: CHUS Fleurimont
state: Quebec
city: Concepción
country: Chile
facility: Hospital Clínico Reg. de Concepción "Dr. G. Grant Benavente"
city: Providencia, Santiago De Chile
country: Chile
facility: Instituto Nacional del Tórax
city: Talca
country: Chile
facility: Centro de Investigación del Maule
city: Beijing
country: China
facility: Peking Union Medical College Hospital
city: Guangzhou
country: China
facility: First Affiliated Hospital of Guangzhou Medical University
city: Nanjing
country: China
facility: Nanjing Drum Tower Hospital
city: Shenyang
country: China
facility: The First Hospital of Chinese Medical University
city: Bobigny
country: France
facility: HOP Avicenne
city: Bron
country: France
facility: HOP Louis Pradel
city: Caen
country: France
facility: HOP Côte de Nacre
city: Clamart
country: France
facility: HOP d'Instruction des Armées Percy
city: Lille
country: France
facility: HOP Calmette
city: Marseille
country: France
facility: HOP Nord
city: Montpellier
country: France
facility: HOP Arnaud de Villeneuve
city: Nice
country: France
facility: HOP Pasteur
city: Paris
country: France
facility: HOP Bichat
city: Reims
country: France
facility: HOP Maison Blanche
city: Rennes
country: France
facility: HOP Pontchaillou
city: Strasbourg
country: France
facility: HOP Civil
city: Tours
country: France
facility: HOP Bretonneau
city: Bonn
country: Germany
facility: Universitätsklinikum Bonn AöR
city: Coswig
country: Germany
facility: Fachkrankenhaus Coswig GmbH
city: Donaustauf
country: Germany
facility: Klinik Donaustauf
city: Essen
country: Germany
facility: Ruhrlandklinik, Westdeutsches Lungenzentrum am Universitätsklinikum Essen gGmbH
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Heidelberg
country: Germany
facility: Thoraxklinik-Heidelberg gGmbH am Universitätsklinikum Heidelberg
city: Solingen
country: Germany
facility: Wissenschaftliches Institut Bethanien
city: Tübingen
country: Germany
facility: Universitätsklinikum Tübingen
city: Wuppertal
country: Germany
facility: Petrus-Krankenhaus
city: Catania
country: Italy
facility: A.O.U. Policlinico Vittorio Emanuele
city: FORLì
country: Italy
facility: Ospedale "G.B. Morgagni - L. Pierantoni" ausl forli
city: Modena
country: Italy
facility: Azienda Ospedaliera Policlinico di Modena
city: Monza
country: Italy
facility: A.O. San Gerardo di Monza
city: Roma
country: Italy
facility: Policlinico Gemelli
city: Siena
country: Italy
facility: A.O.U. Senese Policlinico Santa Maria alle Scotte
city: Aichi, Seto
country: Japan
facility: Tosei General Hospital
city: Fukuoka, Kurume
country: Japan
facility: Kurume University Hospital
city: Hokkaido, Sapporo
country: Japan
facility: Sapporo Medical University Hospital
city: Hyogo, Himeji
country: Japan
facility: National Hospital Organization Himeji Medical Center
city: Hyogo, Kobe
country: Japan
facility: Kobe City Medical Center General Hospital
city: Ibaraki, Naka-gun
country: Japan
facility: Ibarakihigashi National Hospial
city: Kanagawa, Yokohama
country: Japan
facility: Kanagawa Cardiovascular and Respiratory Center
city: Kumamoto, Kumamoto
country: Japan
facility: Saiseikai Kumamoto Hospital
city: Miyagi, Sendai
country: Japan
facility: Tohoku University Hospital
city: Nagasaki, Nagasaki
country: Japan
facility: Nagasaki University Hospital
city: Osaka, Sakai
country: Japan
facility: National Hospital Organization Kinki-Chuo Chest Medical Center
city: Osaka, Takatsuki
country: Japan
facility: Osaka Medical College Hospital
city: Shizuoka, Hamamatsu
country: Japan
facility: Hamamatsu University Hospital
city: Tochigi, Shimotsuke
country: Japan
facility: Jichi Medical University Hospital
city: Tokushima, Tokushima
country: Japan
facility: Tokushima University Hospital
city: Tokyo, Bunkyo-ku
country: Japan
facility: Tokyo Medical and Dental University
city: Tokyo, Bunkyo-ku
country: Japan
facility: Nippon Medical School Hospital
city: Tokyo, Minato-ku
country: Japan
facility: Toranomon Hospital
city: Tokyo, Shibuya-ku
country: Japan
facility: JR Tokyo General Hospital
city: Tokyo, Shinjuku-ku
country: Japan
facility: Global Health and Medicine Ctr
city: Bucheon
country: Korea, Republic of
facility: The Catholic University of Korea, Bucheon St.Mary's Hospital
city: Seongnam
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Gdansk
country: Poland
facility: University Clinical Center, Gdansk
city: Katowice
country: Poland
facility: Leszek Giec Upper-Silesian Med.Cent.Silesian Med.Univ.
city: Lodz
country: Poland
facility: Norbert Barlicki University Clinical Hospital No.1, Lodz
city: Warszawa
country: Poland
facility: Nat.Instit.of Tuberculosis&LungDiseases,Outpat.Clin,warszawa
city: Zabrze
country: Poland
facility: Clinical Hospital No. 1, n.a. Prof. Szyszko from Silesian MA
city: Kemerovo
country: Russian Federation
facility: Res.Inst.-Compl.Iss.Cardi.Dis.
city: Moscow
country: Russian Federation
facility: Pulmonology Scientific Research Institute
city: Moscow
country: Russian Federation
facility: Central Scientific Research Insitute of Tuberculosis
city: Moscow
country: Russian Federation
facility: Moscow 1st State Med.Univ.n.a.I.M.Sechenov
city: St. Petersburg
country: Russian Federation
facility: Scientific Research Institute of Pulmonology
city: Yaroslavl
country: Russian Federation
facility: Emergency Clinical Hospital n. a. N. V. Solovyev, Yaroslavl
city: Barcelona
country: Spain
facility: Hospital Santa Creu i Sant Pau
city: Barcelona
country: Spain
facility: Hospital Vall d'Hebron
city: Cádiz
country: Spain
facility: Hospital Puerta del Mar
city: Galdakao
country: Spain
facility: Hospital de Galdakao
city: L'Hospitalet de Llobregat
country: Spain
facility: Hospital de Bellvitge
city: Madrid
country: Spain
facility: Hospital La Princesa
city: Madrid
country: Spain
facility: Hospital La Paz
city: Oviedo
country: Spain
facility: Hospital Central de Asturias
city: Palma de Mallorca
country: Spain
facility: Hospital Son Espases
city: San Cristóbal de La Laguna
country: Spain
facility: Hospital de Canarias
city: Sevilla
country: Spain
facility: Hospital Virgen del Rocío
city: Valencia
country: Spain
facility: Hospital Politècnic La Fe
city: Cardiff
country: United Kingdom
facility: University Hospital Llandough
city: Edinburgh
country: United Kingdom
facility: Royal Infirmary of Edinburgh
city: Leeds
country: United Kingdom
facility: St James's University Hospital
city: London
country: United Kingdom
facility: Royal Brompton Hospital
city: Manchester
country: United Kingdom
facility: Wythenshawe Hospital
city: Stoke-on-Trent
country: United Kingdom
facility: Royal Stoke University Hospital
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References:
citation: Ogura T, Suda T, Inase N, Nishioka Y, Azuma A, Okamoto M, Takizawa A, Ito T, Rohr KB, Inoue Y. Effects of nintedanib on disease progression and safety in Japanese patients with progressive fibrosing interstitial lung diseases: Further subset analysis from the whole INBUILD trial. Respir Investig. 2022 Nov;60(6):787-797. doi: 10.1016/j.resinv.2022.06.009. Epub 2022 Aug 1.
citation: Cottin V, Martinez FJ, Jenkins RG, Belperio JA, Kitamura H, Molina-Molina M, Tschoepe I, Coeck C, Lievens D, Costabel U. Safety and tolerability of nintedanib in patients with progressive fibrosing interstitial lung diseases: data from the randomized controlled INBUILD trial. Respir Res. 2022 Apr 7;23(1):85. doi: 10.1186/s12931-022-01974-2.
citation: Swigris JJ, Bushnell DM, Rohr K, Mueller H, Baldwin M, Inoue Y. Responsiveness and meaningful change thresholds of the Living with Pulmonary Fibrosis (L-PF) questionnaire Dyspnoea and Cough scores in patients with progressive fibrosing interstitial lung diseases. BMJ Open Respir Res. 2022 Mar;9(1):e001167. doi: 10.1136/bmjresp-2021-001167.
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