Efficacy and Safety of Nintedanib in Patients With Progressive Fibrosing Interstitial Lung Disease (PF-ILD)
- Registration Number
- NCT02999178
- Lead Sponsor
- Boehringer Ingelheim
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 663
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo - Nintedanib Nintedanib -
- Primary Outcome Measures
Name Time Method Annual Rate of Decline in Forced Vital Capacity - Participants With HRCT Fibrotic Pattern=UIP-like Fibrotic Pattern Only Baseline, 2, 4, 6, 12, 24, 36, 52 weeks after first drug intake (planned post-baseline visits) Forced Vital Capacity (FVC) is the volume of air (measured in milliliter) which can be forcibly exhaled from the lungs after taking the deepest breath possible. Annual rate of decline in Forced Vital Capacity in milliliter (mL) per year in participants with HRCT fibrotic pattern=UIP-like fibrotic pattern only is based on a random coefficient regression with fixed effects for treatment, baseline FVC \[mL\], and including treatment-by-time and baseline-by-time interactions. Within-participant errors are modelled by an unstructured variance-covariance matrix.
Annual Rate of Decline in Forced Vital Capacity - Overall Population Baseline, 2, 4, 6, 12, 24, 36, 52 weeks after first drug intake (planned post-baseline visits) Forced Vital Capacity (FVC) is the volume of air (measured in milliliter) which can be forcibly exhaled from the lungs after taking the deepest breath possible. Overall population consists of all randomized participants with HRCT fibrotic pattern=UIP-like fibrotic pattern only or HRCT fibrotic pattern= Other fibrotic patterns. Annual rate of decline in Forced Vital Capacity in milliliter (mL) per year in the overall population is based on a random coefficient regression with fixed effects for treatment, HRCT fibrotic pattern, and baseline FVC \[mL\], and including treatment-by-time and baseline-by-time interactions. Within-participant errors are modelled by an unstructured variance-covariance matrix.
- Secondary Outcome Measures
Name Time Method Time to Death Over 52 Weeks - Overall Population From first drug intake until date of death or last contact date, up to 372 days Time to death over 52 weeks defined as the time from date of first drug intake until date of death from any cause for participants with known date of death (from any cause) within the first 52 weeks. Participants with no event (death from any cause) or unknown status within the first 52 weeks were censored.
Time to Death Over 52 Weeks - Participants With HRCT Fibrotic Pattern=UIP-like Fibrotic Pattern Only From first drug intake until date of death or last contact date, up to 372 days Time to death over 52 weeks defined as the time from date of first drug intake until date of death from any cause for participants with known date of death (from any cause) within the first 52 weeks. Participants with no event (death from any cause) or unknown status within the first 52 weeks were censored.
Time to First Acute Interstitial Lung Disease (ILD) Exacerbation or Death Over 52 Weeks - Overall Population From first drug intake until date of first acute ILD exacerbation or date of death or last contact date, up to 372 days Time to first acute ILD exacerbation or death over 52 weeks was defined as time to first acute ILD exacerbation or death due to any cause within the first 52 weeks and was computed as earliest of date of first documented acute ILD exacerbation or death - date of first drug intake + 1. Participants alive who did not experience any ILD exacerbation event or with unknown status within the first 52 weeks were censored.
Percentage of Participants With a Relative Decline From Baseline in FVC Percent Predicted of More Than 10 Percent at Week 52 - Overall Population Baseline and up to 52 weeks after first drug intake Forced Vital Capacity (FVC) is the volume of air (measured in milliliter) which can be forcibly exhaled from the lungs after taking the deepest breath possible. Predicted normal values of FVC were calculated according to the Global Lung Initiative. FVC percent predicted (FVC % pred) is the FVC divided by its predicted value in percent. Participants with relative decline from baseline in FVC % pred greater than 10% at week 52 were those participants with a negative relative change from baseline in FVC % pred at week 52 the absolute value of which being greater than 10% and those participants with missing data (worst case analysis).
Absolute Change From Baseline in King's Brief Interstitial Lung Disease Questionnaire (K-BILD) Total Score at Week 52 - Overall Population Baseline, 12, 24, 36, 52 weeks after first drug intake (planned post-baseline visits) King's Brief Interstitial Lung Disease questionnaire (K-BILD) consists of 15 items and 3 domains: breathlessness and activities, psychological, and chest symptoms. Possible score ranges from 0-100, score of 100 representing the best health status. If missing items were \>50% per domain, the domain score was set to missing. If any of the domain scores were missing, the total score was set to missing. Absolute change from baseline in K-BILD Total score at week 52 in the overall population was based on a Mixed Model Repeated Measures (MMRM), with fixed effects for baseline K-BILD Total score, HRCT fibrotic pattern, visit, treatment-by-visit interaction, baseline-by-visit interactions and random effect for participant. Visit was the repeated measure. Within-participant errors were modelled by unstructured variance-covariance matrix.
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 Baseline, 12, 24, 36, 52 weeks after first drug intake (planned post-baseline visits) King's Brief Interstitial Lung Disease questionnaire (K-BILD) consists of 15 items and 3 domains: breathlessness and activities, psychological, and chest symptoms. Possible score ranges from 0-100, score of 100 representing the best health status. If missing items were \>50% per domain, the domain score was set to missing. If any of the domain scores were missing, the total score was set to missing. Absolute change from baseline in K-BILD Total score at week 52 in participants with HRCT fibrotic pattern=UIP-like fibrotic pattern only was based on a Mixed Model Repeated Measures (MMRM), with fixed effects for baseline K-BILD Total score, HRCT fibrotic pattern, visit, treatment-by-visit interaction, baseline-by-visit interactions and random effect for participant. Visit was the repeated measure. Within-participant errors were modelled by unstructured variance-covariance matrix.
Time to First Acute Interstitial Lung Disease (ILD) Exacerbation or Death Over 52 Weeks - Participants With HRCT Fibrotic Pattern=UIP-like Fibrotic Pattern Only From first drug intake until date of first acute ILD exacerbation or date of death or last contact date, up to 372 days Time to first acute ILD exacerbation or death over 52 weeks was defined as time to first acute ILD exacerbation or death due to any cause within the first 52 weeks and was computed as earliest of date of first documented acute ILD exacerbation or death - date of first drug intake + 1. Participants alive who did not experience any ILD exacerbation event or with unknown status within the first 52 weeks were censored.
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 Baseline and up to 52 weeks after first drug intake Forced Vital Capacity (FVC) is the volume of air (measured in milliliter) which can be forcibly exhaled from the lungs after taking the deepest breath possible. Predicted normal values of FVC were calculated according to the Global Lung Initiative. FVC percent predicted (FVC % pred) is the FVC divided by its predicted value in percent. Participants with relative decline from baseline in FVC % pred greater than 5% at week 52 were those participants with a negative relative change from baseline in FVC % pred at week 52 the absolute value of which being greater than 5% and those participants with missing data (worst case analysis).
Time to Death Due to Respiratory Cause Over 52 Weeks - Overall Population From date of first trial drug intake up to date of death from respiratory causes or last contact date, up to 372 days Time to death due to respiratory cause over 52 weeks is defined as the time from date of first drug intake until date of death attributed to respiratory causes (determined by an independent Adjudication Committee) for participants with known date of death (from respiratory causes) within the first 52 weeks. Participants with no event (death from respiratory causes) or unknown status within the first 52 weeks were censored. As less than 4.95% of the total of participants in the analysis population experienced an event, only descriptive statistics were performed, as pre-specified.
Time to Progression or Death Over 52 Weeks - Participants With HRCT Fibrotic Pattern=UIP-like Fibrotic Pattern Only From first drug intake until date of progression or date of death or last contact date, up to 372 days Time to progression or death over 52 weeks is defined as the time from date of first drug intake to date of progression, or date of death (from any cause) if a participant died earlier. Participants with no event (progression or death from any cause) or unknown status were censored. Date of progression is defined as the date when ≥ 10% of absolute decline in FVC percent predicted compared to baseline occured for the first time. Forced Vital Capacity (FVC) is the volume of air (measured in milliliter) which can be forcibly exhaled from the lungs after taking the deepest breath possible. Predicted normal values of FVC were calculated according to the Global Lung Initiative. FVC percent predicted (FVC % pred) is the FVC divided by its predicted value in percent.
Percentage of Participants With a Relative Decline From Baseline in FVC Percent Predicted of More Than 5 Percent at Week 52 - Overall Population Baseline and up to 52 weeks after first drug intake Forced Vital Capacity (FVC) is the volume of air (measured in milliliter) which can be forcibly exhaled from the lungs after taking the deepest breath possible. Predicted normal values of FVC were calculated according to the Global Lung Initiative. FVC percent predicted (FVC % pred) is the FVC divided by its predicted value in percent. Participants with relative decline from baseline in FVC % pred greater than 5% at week 52 were those participants with a negative relative change from baseline in FVC % pred at week 52 the absolute value of which being greater than 5% and those participants with missing data (worst case analysis).
Time to Death Due to Respiratory Cause Over 52 Weeks - Participants With HRCT Fibrotic Pattern=UIP-like Fibrotic Pattern Only From date of first trial drug intake up to date of death from respiratory causes or last contact date, up to 372 days Time to death due to respiratory cause over 52 weeks is defined as the time from date of first drug intake until date of death attributed to respiratory causes (determined by an independent Adjudication Committee) for participants with known date of death (from respiratory causes) within the first 52 weeks. Participants with no event (death from respiratory causes) or unknown status within the first 52 weeks were censored. As less than 4.95% of the total of participants in the analysis population experienced an event, only descriptive statistics were performed, as pre-specified.
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 Baseline and up to 52 weeks after first drug intake Forced Vital Capacity (FVC) is the volume of air (measured in milliliter) which can be forcibly exhaled from the lungs after taking the deepest breath possible. Predicted normal values of FVC were calculated according to the Global Lung Initiative. FVC percent predicted (FVC % pred) is the FVC divided by its predicted value in percent. Participants with relative decline from baseline in FVC % pred greater than 10% at week 52 were those participants with a negative relative change from baseline in FVC % pred at week 52 the absolute value of which being greater than 10% and those participants with missing data (worst case analysis).
Time to Progression or Death Over 52 Weeks - Overall Population From first drug intake until date of progression or date of death or last contact date, up to 372 days Time to progression or death over 52 weeks is defined as the time from date of first drug intake to date of progression, or date of death (from any cause) if a participant died earlier. Participants with no event (progression or death from any cause) or unknown status were censored. Date of progression is defined as the date when ≥ 10% of absolute decline in FVC percent predicted compared to baseline occured for the first time. Forced Vital Capacity (FVC) is the volume of air (measured in milliliter) which can be forcibly exhaled from the lungs after taking the deepest breath possible. Predicted normal values of FVC were calculated according to the Global Lung Initiative. FVC percent predicted (FVC % pred) is the FVC divided by its predicted value in percent.
Absolute Change From Baseline in Living With Pulmonary Fibrosis (L-PF) Symptoms Dyspnea Domain Score at Week 52 - Overall Population Baseline, 12, 24, 36, 52 weeks after first drug intake (planned post-baseline visits) Living with Pulmonary Fibrosis (L-PF) questionnaire is a 44 item questionnaire with two modules Symptoms (23 items) and Impacts (21 items) where the symptoms module yields three domain scores dyspnea, cough and fatigue as well as a total symptoms score (impacts module yields a single impacts score). L-PF Symptoms dyspnea domain score (dyspnea score) ranges from 0-100, the higher the score the greater the impairment. If missing items were ≥50 % within a score, then the corresponding score was set to missing. Absolute change from baseline in dyspnea score at week 52 is based on a Mixed Model Repeated Measures, with fixed effects for baseline dyspnea score, HRCT fibrotic pattern, visit, treatment-by-visit interaction, baseline dyspnea score-by-visit interaction and random effect for participant, visit as repeated measure. The Adjusted mean is based on all analysed participants in the model (not only participants with a baseline and measurement at week 52).
Absolute Change From Baseline in L-PF Symptoms Dyspnea Domain Score at Week 52 - Participants With HRCT Fibrotic Pattern=UIP-like Fibrotic Pattern Only Baseline, 12, 24, 36, 52 weeks after first drug intake (planned post-baseline visits) Living with Pulmonary Fibrosis (L-PF) questionnaire is a 44 item questionnaire with two modules Symptoms (23 items) and Impacts (21 items) where the symptoms module yields three domain scores dyspnea, cough and fatigue as well as a total symptoms score (impacts module yields a single impacts score). L-PF Symptoms dyspnea domain score (dyspnea score) ranges from 0-100, the higher the score the greater the impairment. If missing items were ≥50 % within a score, then the corresponding score was set to missing. Absolute change from baseline in dyspnea score at week 52 is based on a Mixed Model Repeated Measures, with fixed effects for baseline dyspnea score, visit, treatment-by-visit interaction, baseline dyspnea score-by-visit interaction and random effect for participant, visit as repeated measure. The Adjusted mean is based on all analysed participants in the model (not only participants with a baseline and measurement at week 52).
Absolute Change From Baseline in L-PF Symptoms Cough Domain Score at Week 52 - Overall Population Baseline, 12, 24, 36, 52 weeks after first drug intake (planned post-baseline visits) Living with Pulmonary Fibrosis (L-PF) questionnaire is a 44 item questionnaire with two modules Symptoms (23 items) and Impacts (21 items) where the symptoms module yields three domain scores dyspnea, cough and fatigue as well as a total symptoms score (impacts module yields a single impacts score). L-PF Symptoms cough domain score (cough score) ranges from 0-100, the higher the score the greater the impairment. If missing items were ≥50 % within a score, then the corresponding score was set to missing. Absolute change from baseline in cough score at week 52 is based on a Mixed Model Repeated Measures, with fixed effects for baseline cough score, HRCT fibrotic pattern, visit, treatment-by-visit interaction, baseline cough score-by-visit interaction and random effect for participant, visit as repeated measure. The Adjusted mean is based on all analysed participants in the model (not only participants with a baseline and measurement at week 52).
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 Baseline, 12, 24, 36, 52 weeks after first drug intake (planned post-baseline visits) Living with Pulmonary Fibrosis (L-PF) questionnaire is a 44 item questionnaire with two modules Symptoms (23 items) and Impacts (21 items) where the symptoms module yields three domain scores dyspnea, cough and fatigue as well as a total symptoms score (impacts module yields a single impacts score). L-PF Symptoms cough domain score (cough score) ranges from 0-100, the higher the score the greater the impairment. If missing items were ≥50 % within a score, then the corresponding score was set to missing. Absolute change from baseline in cough score at week 52 is based on a Mixed Model Repeated Measures, with fixed effects for baseline cough score, visit, treatment-by-visit interaction, baseline cough score-by-visit interaction and random effect for participant, visit as repeated measure. The Adjusted mean is based on all analysed participants in the model (not only participants with a baseline and measurement at week 52).
Trial Locations
- Locations (152)
The Ohio State University Wexner Medical Center
🇺🇸Columbus, Ohio, United States
Baylor University Medical Center
🇺🇸Dallas, Texas, United States
ULB Hopital Erasme
🇧🇪Bruxelles, Belgium
HOP Calmette
🇫🇷Lille, France
Nanjing Drum Tower Hospital
🇨🇳Nanjing, China
Hospital Son Espases
🇪🇸Palma de Mallorca, Spain
University of Kentucky Medical Center
🇺🇸Lexington, Kentucky, United States
University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
Centro Dr. Lazaro Langer S.R.L
🇦🇷Alberdi Sur, Argentina
INSARES
🇦🇷Mendoza, Argentina
First Affiliated Hospital of Guangzhou Medical University
🇨🇳Guangzhou, China
Hospital Puerta del Mar
🇪🇸Cádiz, Spain
Peking Union Medical College Hospital
🇨🇳Beijing, China
CHUS Fleurimont
🇨🇦Sherbrooke, Quebec, Canada
Fachkrankenhaus Coswig GmbH
🇩🇪Coswig, Germany
Klinik Donaustauf
🇩🇪Donaustauf, Germany
Tohoku University Hospital
🇯🇵Miyagi, Sendai, Japan
University Hospital Llandough
🇬🇧Cardiff, United Kingdom
Royal Infirmary of Edinburgh
🇬🇧Edinburgh, United Kingdom
Hospital Politècnic La Fe
🇪🇸Valencia, Spain
Hospital de Canarias
🇪🇸San Cristóbal de La Laguna, Spain
Hospital La Princesa
🇪🇸Madrid, Spain
Hospital de Galdakao
🇪🇸Galdakao, Spain
Hospital La Paz
🇪🇸Madrid, Spain
Hospital de Bellvitge
🇪🇸L'Hospitalet de Llobregat, Spain
The First Hospital of Chinese Medical University
🇨🇳Shenyang, China
Cedars-Sinai Medical Center
🇺🇸Los Angeles, California, United States
University of California Los Angeles
🇺🇸Los Angeles, California, United States
Loyola University Medical Center
🇺🇸Maywood, Illinois, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
University of Chicago
🇺🇸Chicago, Illinois, United States
The Lung Research Center, LLC
🇺🇸Chesterfield, Missouri, United States
Columbia University Medical Center-New York Presbyterian Hospital
🇺🇸New York, New York, United States
NewYork-Presbyterian/Weill Cornell Medical Center
🇺🇸New York, New York, United States
Icahn School of Medicine at Mount Sinai
🇺🇸New York, New York, United States
Penn State Milton S. Hershey Medical Center
🇺🇸Hershey, Pennsylvania, United States
Temple University Hospital
🇺🇸Oaks, Pennsylvania, United States
University of Texas Southwestern Medical Center
🇺🇸Dallas, Texas, United States
Texas Pul & Crit Care Conslt
🇺🇸Fort Worth, Texas, United States
Inova Fairfax Medical Campus
🇺🇸Falls Church, Virginia, United States
Pulmonary Associates of Richmond, Inc.
🇺🇸Richmond, Virginia, United States
Pulmonary and Sleep of Tampa Bay
🇺🇸Brandon, Florida, United States
Emory University
🇺🇸Atlanta, Georgia, United States
Jichi Medical University Hospital
🇯🇵Tochigi, Shimotsuke, Japan
Leszek Giec Upper-Silesian Med.Cent.Silesian Med.Univ.
🇵🇱Katowice, Poland
Moscow 1st State Med.Univ.n.a.I.M.Sechenov
🇷🇺Moscow, Russian Federation
Hospital Santa Creu i Sant Pau
🇪🇸Barcelona, Spain
Hospital Vall d'Hebron
🇪🇸Barcelona, Spain
Hospital Central de Asturias
🇪🇸Oviedo, Spain
Hospital Virgen del Rocío
🇪🇸Sevilla, Spain
St James's University Hospital
🇬🇧Leeds, United Kingdom
Royal Stoke University Hospital
🇬🇧Stoke-on-Trent, United Kingdom
University of South Carolina
🇺🇸Columbia, South Carolina, United States
University of Florida College of Medicine
🇺🇸Jacksonville, Florida, United States
Pulmonary and Sleep Specialists
🇺🇸Danbury, Connecticut, United States
UZ Leuven
🇧🇪Leuven, Belgium
Azienda Ospedaliera Policlinico di Modena
🇮🇹Modena, Italy
Yale University School of Medicine
🇺🇸New Haven, Connecticut, United States
Spectrum Health
🇺🇸Grand Rapids, Michigan, United States
University of Maryland School of Medicine
🇺🇸Baltimore, Maryland, United States
Johns Hopkins Hospital
🇺🇸Baltimore, Maryland, United States
Dartmouth-Hitchcock Medical Center
🇺🇸Lebanon, New Hampshire, United States
Pulmonary and Critical Care Associates of Baltimore
🇺🇸Towson, Maryland, United States
Instituto Nacional del Tórax
🇨🇱Providencia, Santiago De Chile, Chile
HOP Louis Pradel
🇫🇷Bron, France
HOP d'Instruction des Armées Percy
🇫🇷Clamart, France
Instituto Médico de la Fundación Estudios Clínicos
🇦🇷Rosario, Argentina
Centro de Investigaciones Metabólicas (CINME)
🇦🇷C.a.b.a, Argentina
CEMER-Centro Medico De Enfermedades Respiratorias
🇦🇷Florida, Argentina
Centre Hospitalier Universitaire de Liège
🇧🇪Angleur, Belgium
Sanatorio Güemes
🇦🇷Ciudad Autónoma de Bs As, Argentina
Toronto General Hospital
🇨🇦Toronto, Ontario, Canada
Yvoir - UNIV UCL de Mont-Godinne
🇧🇪Yvoir, Belgium
Hospital Clínico Reg. de Concepción "Dr. G. Grant Benavente"
🇨🇱Concepción, Chile
HOP Avicenne
🇫🇷Bobigny, France
HOP Maison Blanche
🇫🇷Reims, France
HOP Pontchaillou
🇫🇷Rennes, France
Universitätsklinikum Tübingen
🇩🇪Tübingen, Germany
Nagasaki University Hospital
🇯🇵Nagasaki, Nagasaki, Japan
Nat.Instit.of Tuberculosis&LungDiseases,Outpat.Clin,warszawa
🇵🇱Warszawa, Poland
Res.Inst.-Compl.Iss.Cardi.Dis.
🇷🇺Kemerovo, Russian Federation
Centro de Investigación del Maule
🇨🇱Talca, Chile
HOP Côte de Nacre
🇫🇷Caen, France
HOP Nord
🇫🇷Marseille, France
HOP Arnaud de Villeneuve
🇫🇷Montpellier, France
HOP Bretonneau
🇫🇷Tours, France
Medizinische Hochschule Hannover
🇩🇪Hannover, Germany
HOP Pasteur
🇫🇷Nice, France
Universitätsklinikum Bonn AöR
🇩🇪Bonn, Germany
Ruhrlandklinik, Westdeutsches Lungenzentrum am Universitätsklinikum Essen gGmbH
🇩🇪Essen, Germany
HOP Bichat
🇫🇷Paris, France
HOP Civil
🇫🇷Strasbourg, France
Thoraxklinik-Heidelberg gGmbH am Universitätsklinikum Heidelberg
🇩🇪Heidelberg, Germany
Wissenschaftliches Institut Bethanien
🇩🇪Solingen, Germany
Petrus-Krankenhaus
🇩🇪Wuppertal, Germany
A.O.U. Policlinico Vittorio Emanuele
🇮🇹Catania, Italy
Ospedale "G.B. Morgagni - L. Pierantoni" ausl forli
🇮🇹FORLì, Italy
A.O. San Gerardo di Monza
🇮🇹Monza, Italy
A.O.U. Senese Policlinico Santa Maria alle Scotte
🇮🇹Siena, Italy
Kurume University Hospital
🇯🇵Fukuoka, Kurume, Japan
National Hospital Organization Himeji Medical Center
🇯🇵Hyogo, Himeji, Japan
Tosei General Hospital
🇯🇵Aichi, Seto, Japan
National Hospital Organization Kinki-Chuo Chest Medical Center
🇯🇵Osaka, Sakai, Japan
Policlinico Gemelli
🇮🇹Roma, Italy
Sapporo Medical University Hospital
🇯🇵Hokkaido, Sapporo, Japan
Kobe City Medical Center General Hospital
🇯🇵Hyogo, Kobe, Japan
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Ibarakihigashi National Hospial
🇯🇵Ibaraki, Naka-gun, Japan
Tokushima University Hospital
🇯🇵Tokushima, Tokushima, Japan
Tokyo Medical and Dental University
🇯🇵Tokyo, Bunkyo-ku, Japan
Nippon Medical School Hospital
🇯🇵Tokyo, Bunkyo-ku, Japan
JR Tokyo General Hospital
🇯🇵Tokyo, Shibuya-ku, Japan
Kanagawa Cardiovascular and Respiratory Center
🇯🇵Kanagawa, Yokohama, Japan
Osaka Medical College Hospital
🇯🇵Osaka, Takatsuki, Japan
Saiseikai Kumamoto Hospital
🇯🇵Kumamoto, Kumamoto, Japan
Global Health and Medicine Ctr
🇯🇵Tokyo, Shinjuku-ku, Japan
The Catholic University of Korea, Bucheon St.Mary's Hospital
🇰🇷Bucheon, Korea, Republic of
Hamamatsu University Hospital
🇯🇵Shizuoka, Hamamatsu, Japan
Toranomon Hospital
🇯🇵Tokyo, Minato-ku, Japan
University Clinical Center, Gdansk
🇵🇱Gdansk, Poland
Clinical Hospital No. 1, n.a. Prof. Szyszko from Silesian MA
🇵🇱Zabrze, Poland
Central Scientific Research Insitute of Tuberculosis
🇷🇺Moscow, Russian Federation
Seoul National University Bundang Hospital
🇰🇷Seongnam, Korea, Republic of
Norbert Barlicki University Clinical Hospital No.1, Lodz
🇵🇱Lodz, Poland
Emergency Clinical Hospital n. a. N. V. Solovyev, Yaroslavl
🇷🇺Yaroslavl, Russian Federation
Scientific Research Institute of Pulmonology
🇷🇺St. Petersburg, Russian Federation
Pulmonology Scientific Research Institute
🇷🇺Moscow, Russian Federation
Wythenshawe Hospital
🇬🇧Manchester, United Kingdom
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
University of California San Francisco
🇺🇸San Francisco, California, United States
National Jewish Health
🇺🇸Denver, Colorado, United States
University of Miami
🇺🇸Miami, Florida, United States
Brigham and Women's Hospital
🇺🇸Boston, Massachusetts, United States
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
University of Minnesota Masonic Cancer Center
🇺🇸Minneapolis, Minnesota, United States
Mayo Clinic, Rochester
🇺🇸Rochester, Minnesota, United States
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
The Oregon Clinic
🇺🇸Portland, Oregon, United States
Henry Ford Health System
🇺🇸Detroit, Michigan, United States
Creighton University
🇺🇸Omaha, Nebraska, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Houston Methodist Hospital
🇺🇸Houston, Texas, United States
Diagnostics Research Group
🇺🇸San Antonio, Texas, United States
Medical Arts and Research Center (MARC)
🇺🇸San Antonio, Texas, United States
University of Utah Health Sciences Center
🇺🇸Salt Lake City, Utah, United States
University of California Davis
🇺🇸Sacramento, California, United States
Pulmonary and Critical Care Medicine
🇺🇸Ann Arbor, Michigan, United States
Southeastern Research Center
🇺🇸Winston-Salem, North Carolina, United States
Royal Brompton Hospital
🇬🇧London, United Kingdom
University of Kansas Medical Center
🇺🇸Kansas City, Kansas, United States
Concordia Hospital
🇨🇦Winnipeg, Manitoba, Canada
St. Joseph's Healthcare Hamilton
🇨🇦Hamilton, Ontario, Canada