Study to Assess Efficacy and Safety of Baloxavir Marboxil In Combination With Standard-of-Care Neuraminidase Inhibitor In Hospitalized Participants With Severe Influenza
- Registration Number
- NCT03684044
- Lead Sponsor
- Hoffmann-La Roche
- Brief Summary
This study will evaluate the efficacy, safety, and pharmacokinetics of baloxavir marboxil in combination with a standard-of-care (SOC) neuraminidase inhibitor (NAI) (i.e., oseltamivir, zanamivir, or peramivir) compared with a matching placebo in combination with a SOC NAI in hospitalized patients with influenza.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 363
- Adult participants: Signed informed consent by any participant capable of giving consent, or, where the participant is not capable of giving consent, by his or her legal/authorized representative
- Adolescent participants not able to legally consent: written informed consent for study participation is obtained from participant's parents or legal guardian, with assent as appropriate by the participant, depending on the participant's level of understanding and capability to provide assent
- Participants who require hospitalization for severe influenza or acquire influenza during hospitalization, the severity of which requires an extension of hospitalization
- Diagnosis of influenza A and/or B by a positive Rapid Influenza Diagnostic Test (RIDT) or reverse transcriptase-polymerase chain reaction (RT-PCR)
- The time interval between the onset of symptoms and randomization is within 96 hours
- A score of ≥4 based on the National Early Warning Score 2 (NEWS2)
- Participants will require objective criteria of seriousness defined by at least one of the following criteria:
- Requires ventilation or supplemental oxygen to support respiration
- Has a complication related to influenza that requires hospitalization (e.g., pneumonia, central nervous system involvement, myositis, rhabdomyolysis, acute exacerbation of chronic kidney disease, asthma or chronic obstructive pulmonary disease (COPD), severe dehydration, myocarditis, pericarditis, exacerbation of ischemic heart disease)
- For women of childbearing potential: Agreement to remain abstinent or use contraceptive methods with a failure rate of < 1% per year during the treatment period and for 28 days after the last dose of study treatment. Hormonal contraceptive methods must be supplemented by a barrier method.
- Participants who have received more than 48 hours of antiviral treatment for the current influenza infection prior to screening
- Participants who have received baloxavir marboxil for the current influenza infection
- Known contraindication to neuraminidase inhibitors
- Participants hospitalized for exclusively social reasons (e.g., lack of caregivers at home)
- Participants expected to die or be discharged within 48 hours, according to the investigator's judgement
- Participants weighing < 40 kg
- Participants with known severe renal impairment (estimated glomerular filtration rate < 30 mL/min/1.73 m2) or receiving continuous renal replacement therapy, hemodialysis, peritoneal dialysis
- Participants with any of the following laboratory abnormalities detected within 24 hours prior to or during screening (according to local laboratory reference ranges:
- Alanine Transaminase (ALT) or Aspartate Transaminase (AST) level > 5 times the upper limit of normal (ULN) OR
- ALT or AST > 3 times the ULN and total bilirubin level > 2 times the ULN
- Pregnant or breastfeeding, or positive pregnancy test in a predose examination, or intending to become pregnant during the study or within 28 days after the last dose of study treatment
- Exposure to an investigational drug within 5 half-lives or 30 days (whichever is longer) of randomization
- Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the participant's safe participation in and completion of the study
- Known hypersensitivity to baloxavir marboxil or the drug product excipients
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Participants will receive at least two doses of placebo on Day 1 and 4. A third dose of placebo will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with SOC NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice. Baloxavir Marboxil Baloxavir Marboxil Participants will receive at least two doses of baloxavir marboxil on Days 1 and 4. A third dose of Baloxavir will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with SOC NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.
- Primary Outcome Measures
Name Time Method Time to Clinical Improvement Up to Day 35 Time to Clinical Improvement (TTCI) is defined as Time to Hospital Discharge OR Time to NEWS2 (National Early Warning Score 2) of ≤ 2 maintained for 24 hours.
- Secondary Outcome Measures
Name Time Method Time to Hospital Discharge Up to Day 35 Mortality Rate at Day 7 Up to Day 7 Duration of ICU Stay Up to Day 35 Area Under the Curve in Virus Titer Days 1, 2, 3, 4, 5, 7, and 10 Time to Clinical Response Up to Day 35 Time to Clinical Response is based on temperature ranges, oxygen saturation, respiratory status, heart rate, and hospitalization status.
Duration of Mechanical Ventilation Up to Day 35 Percentage of Participants With Post-Treatment Influenza-Related Complications Up to Day 35 Influenza-related complications included pneumonia, myositis or rhabdomyolysis, encephalitis or encephalopathy, myocarditis and/or pericarditis, otitis media, sinusitis, exacerbation of COPD/asthma, sepsis, acute lung injury or acute respiratory distress syndrome.
Time to NEWS2 of ≤ 2 Maintained for 24 Hours Up to Day 35 A score of 0 (Range 0 - 3) indicates normal health conditions.
Percentage of Participants on Mechanical Ventilation Up to Day 35 Time to Clinical Failure Up to Day 35 Time to clinical failure, defined as the time to death, mechanical ventilation, or ICU admission, corresponding to ordinal scale categories 6, 5, and 4, respectively, from baseline
Response Rates of the 6-Point Ordinal Scale at Day 7 Day 7 The ordinal scale categories are:
Category 1) Discharged (or "ready for discharge") Category 2) Non-ICU hospital ward (or "ready for hospital ward") not requiring supplemental oxygen/non-invasive ventilation Category 3) Non-ICU hospital ward (or "ready for hospital ward") requiring supplemental oxygen/non-invasive ventilation Category 4) ICU without mechanical (invasive) ventilation (or "ready for ICU admission") Category 5) Mechanical (invasive) ventilation Category 6) DeathChange From Baseline in Influenza Virus Titer at Each Timepoint Days 2, 3, 4, 5, 7, and 10 Influenza virus titer is the quantity of influenza virus in a given volume within the samples obtained from nasal swabs. If influenza virus titer was less than the lower limit of quantification, the virus titer was imputed as 0.749 (log10TCID50/mL). A lower value indicates lower viral titer.
Time to Cessation of Viral Shedding by RT-PCR Screening (baseline) and on Days 2, 3, 4, 5, 7, and 10 Time to cessation of viral shedding by RT-PCR, in hours, is defined as the time between the initiation of study treatment and first time when the virus RNA by RT-PCR is below the limit of detection (2.05 for flu A and 2.83 for flu B log10 virus particles/mL)
Percentage of Participants With Any Post-Treatment ALT and AST Above Baseline and >3 × ULN, >5 × ULN, >10 × ULN Up to Day 35 ALT = alanine aminotransferase AST = aspartate transaminase
Percentage of Participants Requiring ICU Stay Up to Day 35 Mortality Rate at Day 28 Up to Day 28 Time to Cessation of Viral Shedding by Virus Titer Screening (baseline) and on Days 2, 3, 4, 5, 7, and 10 Time to cessation of viral shedding by virus titer is defined as the time, in hours, between the initiation of study treatment and first time when the influenza virus titer is below the limit of detection (0.75 log10 TCID50/mL)
Change From Baseline in the Amount of Virus RNA (RT-PCR) at Each Timepoint Days 2, 3, 4, 5, 7, and 10 If the amount of virus RNA was less than the lower limit of quantification, the amount of virus RNA was imputed as 2.18 for flu A and 2.93 for flu B (log10 virus particles/mL)
Percentage of Participants Positive by RT-PCR at Each Timepoint Days 2, 3, 4, 5, 7, and 10 If the amount of virus RNA was less than the lower limit of quantification, the amount of virus RNA was imputed as 2.18 for flu A and 2.93 for flu B (log10 virus particles/mL)
Plasma Concentration of Baloxavir (Active Metabolite) at Specified Time Points Day 1, 2, 4, 5, 7 and 8 Area Under the Concentration to Time Curve From Time 0 to 72 Hours (AUC0-72) of Baloxavir 0, 0.5, 2, 4, 10, 24, 72 hours from dose on Day 1 and on Day 4, and Day 7, Day 8 Apparent Half-Life (T1/2) of Baloxavir 0, 0.5, 2, 4, 10, 24, 72 hours from dose on Day 1 and on Day 4, and Day 7, Day 8 Percentage of Participants With Positive Influenza Virus Titer at Each Timepoint Days 2, 3, 4, 5, 7, and 10 Influenza virus titer is the quantity of influenza virus in a given volume within the samples obtained from nasal swabs. If influenza virus titer was less than the lower limit of quantification, the virus titer was imputed as 0.749 (log10 TCID50/mL). A lower value indicates lower viral titer.
Area Under the Curve in the Amount of Virus RNA (RT-PCR) Days 1, 2, 3, 4, 5, 7, and 10 Percentage of Participants With AEs and SAEs Leading to Discontinuation From Treatment Up to Day 35 Discontinuation from study treatment.
Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Up to Day 35 An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not considered related to the medicinal (investigational) product. A serious adverse event (SAE) is any significant hazard, contraindication, side effect that is fatal or life-threatening, requires hospitalization or prolongation of an existing hospitalization, results in persistent or significant disability/ incapacity, is a congenital anomaly/ birth defect, is medically significant or requires intervention to prevent one or other of the outcomes listed above.
Maximum Plasma Concentration (Cmax) of Baloxavir 0, 0.5, 2, 4, 10, 24, 72 hours from dose on Day 1 and on Day 4, and Day 7, Day 8 Concentration at 24 Hours (C24) of Baloxavir 0, 0.5, 2, 4, 10, 24, 72 hours from dose on Day 1 and on Day 4, and Day 7, Day 8
Trial Locations
- Locations (170)
Naha City Hospital
🇯🇵Naha, Japan
Social Corporation Keigakukai Minamiosaka Hosupital
🇯🇵Osaka, Japan
National Hospital Organaization Shibukawa Medical Center
🇯🇵Shibukawa, Japan
Saka General Hospital
🇯🇵Shiogama, Japan
The Catholic University of Korea Incheon St. Mary's Hospital
🇰🇷Incheon, Korea, Republic of
Seoul National University Bundang Hospital
🇰🇷Seongnam-si, Korea, Republic of
Korea University Anam Hospital
🇰🇷Seoul, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
ChungAng University Hospital
🇰🇷Seoul, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Hallym University Kangnam Sacred Heart Hospital
🇰🇷Seoul, Korea, Republic of
Wellington Hospital
🇳🇿Wellington, New Zealand
General Hospital Dr Radivoj Simonovic Sombor
🇷🇸Sombor, Serbia
Hospital Universitario Marques de Valdecilla
🇪🇸Santander, Cantabria, Spain
Hospital Universitario de Torrejon
🇪🇸Torrejon de Ardoz, Madrid, Spain
Hospital General Universitario de Alicante
🇪🇸Alicante, Spain
Hospital del Mar
🇪🇸Barcelona, Spain
Hospital Universitario Vall d'Hebron - PPDS
🇪🇸Barcelona, Spain
Sahlgrenska Universitetssjukhuset
🇸🇪Goteborg, Sweden
Hospital de La Ribera
🇪🇸Valencia, Spain
Hospital Universitario Virgen Macarena
🇪🇸Sevilla, Spain
Hospital Universitario Fundacion Jimenez Diaz.
🇪🇸Madrid, Spain
Hospital General Universitario Reina Sofia; Servicio de Nefrologia
🇪🇸Murcia, Spain
Akdeniz University Medical Faculty
🇹🇷Antalya, Turkey
Karadeniz Technical University Faculty of Medicine
🇹🇷Trabzon, Turkey
Skånes Universitetssjukhus Malmö; Infektionskliniken
🇸🇪Malmö, Sweden
Hacettepe University Medical Faculty
🇹🇷Ankara, Turkey
Selcuk University Medical Faculty; Internal Medicine
🇹🇷Konya, Turkey
MI Vinnytsia Regional Clinical Children's Infectious Hospital; Infectiuos Box department
🇺🇦Vinnytsia, KIEV Governorate, Ukraine
Municipal Institution City Clinical Infectious Diseases Hospital
🇺🇦Odesa, Ukraine
Barnum Medical Research, Inc.
🇺🇸Natchitoches, Louisiana, United States
Instituto Medico Platense
🇦🇷La Plata, Argentina
Hopital Erasme; Chest Medicine, Cardiac & Thoracic Surgery
🇧🇪Bruxelles, Belgium
Cliniques Universitaires Saint-Luc; Hematology
🇧🇪Bruxelles, Belgium
MHAT Stamen Iliev AD; Pharmacy
🇧🇬Montana, Bulgaria
University Mulitiprofile Hospital for Active Treatment Sveti Georgi EAD; Pharmacy
🇧🇬Plovdiv, Bulgaria
UZ Leuven
🇧🇪Leuven, Belgium
Multiprofile Hospital For Active Treatment Sveta Ekaterina Dimitrovgrad EOOD; Internal Diseases
🇧🇬Dimitrovgrad, Bulgaria
Specialized Hospital for Active Treatment of Pneumophthisiatric Diseases - Haskovo EOOD
🇧🇬Haskovo, Bulgaria
Specialized Hospital for Active Treatment of Pneumophthisiatric Diseases Dr. D. Gramatikov - Ruse
🇧🇬Ruse, Bulgaria
Multiprofile Hospital for Active Treatment - Samokov EOOD
🇧🇬Samokov, Bulgaria
Carlson Urology
🇨🇦Calgary, Alberta, Canada
Multiprofile Hospital For Active Treatment Sliven То Military Hospital Sofia; Pharmacy
🇧🇬Sliven, Bulgaria
Military Medical Academy Multiprofile Hospital for Active Treatment - Sofia; Pharmacy
🇧🇬Sofia, Bulgaria
Peter Lougheed Centre
🇨🇦Calgary, Alberta, Canada
Specialized Hospital for Active Treatment of Pneumophthisiatric Diseases-Vratsa; Pharmacy
🇧🇬Vratsa, Bulgaria
South Health Campus
🇨🇦Calgary, Alberta, Canada
Soroka University Medical Centre
🇮🇱Beer Sheva, Israel
Japanese Red Cross Kumamoto Hospital
🇯🇵Kumamoto-shi, Japan
National Hospital Organization Ibarakihigashi National Hospital; Center for Clinical Research
🇯🇵Naka-gun, Japan
Tokyo Shinagawa Hospital Medical Corporation Association Tokyokyojuno-kai
🇯🇵Shinagawa, Japan
Japan Community Health care Organization Nihonmatsu hospital
🇯🇵Nihonmatsu, Japan
Iwase General Hospital
🇯🇵Sukagawa, Japan
Ikazia Ziekenhuis
🇳🇱Rotterdam, Netherlands
Local incorporated administrative agency Shizuoka City Shizuoka Hospital
🇯🇵Shizuoka, Japan
Hospital Universitario Dr. Jose Eleuterio González; Enfermedades Pulmonares Crónicas
🇲🇽Monterrey, Mexico
Leids Universitair Medisch Centrum; C5-P Stafcentrum Hartziekten
🇳🇱Leiden, Netherlands
Hospital Alberto Sabogal Sologuren
🇵🇪Callao, Peru
Dr. Victor Babes Clinical Hospital For Tropical and Infectious Diseases
🇷🇴Bucharest, Romania
Spitalul Clinic de Boli Infectioase
🇷🇴Cluj Napoca, Romania
Center Hospital of the National Center for Global Health and Medicine
🇯🇵Tokyo, Japan
Hospital Sant Joan de Deu - PIN; Unitat de Recerca - Farmacia
🇪🇸Esplugues de Llobregat, Barcelona, Spain
Hospital Mutua de Terrassa
🇪🇸Terrassa, Barcelona, Spain
Nagata Hospital; Department of pulmonary medicine
🇯🇵Yanagawa-shi, Japan
Hospital General de Tijuana
🇲🇽Tijuana, Mexico
Canisius Wilhelmina Ziekenhuis; Department Hematology
🇳🇱Nijmegen, Netherlands
Sibiu Emergency Clinical County Hospital
🇷🇴Sibiu, Romania
Clinical Center of Serbia
🇷🇸Belgrade, Serbia
Instituto Nacional de Ciencias Médicas y Nutricion Dr. Salvador Zubiran; Hamatologia y Oncologia
🇲🇽Mexico, Mexico CITY (federal District), Mexico
Hospital Civil Fray Antonio Alcalde; Instituto de Patologia Infecciosa
🇲🇽Guadalajara, Mexico
Prof. Dr. Matei Bals Institute of Infectious Diseases
🇷🇴Bucharest, Romania
Zuyderland Medisch Centrum - Sittard Geleen
🇳🇱Sittard-Geleen, Netherlands
Universitair Medisch Centrum Utrecht
🇳🇱Utrecht, Netherlands
Hospital Nacional Adolfo Guevara Velasco - ESSALUD; Servicio de Cardiología
🇵🇪Cusco, Peru
Sf.Cuv. Parascheva Infectious Diseases Clinical Hospital
🇷🇴Galati, Romania
Spitalul Clinic de Boli Infectioase "Sfanta Parascheva" Iasi
🇷🇴Iasi, Romania
Clinical Centre of Vojvodina
🇷🇸Nova Sad, Serbia
Institute of Lung Diseases Vojvodina
🇷🇸Sremska Kamenica, Serbia
Sf. Ioan cel Nou Emergency County Hospital
🇷🇴Suceava, Romania
Tan Tock Seng Hospital
🇸🇬Singapore, Singapore
Hospital Universitario Germans Trias i Pujol
🇪🇸Badalona, Barcelona, Spain
Clinical Hospital Center Zvezdara
🇷🇸Belgrade, Serbia
Clinical Center Kragujevac
🇷🇸Kragujevac, Serbia
Clinical Center Nis; Clinic for Pulmonary Diseases and Tuberculosis Knez Selo
🇷🇸Nis, Serbia
Regional Municipal Institution Chernivtsi Regional Clinical Hospital
🇺🇦Chernivtsi, Chernihiv Governorate, Ukraine
Regional Municipal Institution Sumy Regional Infectious Clinical Hospital n.a. Z.Y. Krasovytskyi
🇺🇦Sumy, Katerynoslav Governorate, Ukraine
Communal Non-Commercial Enterprise "Vinnytsia City Clinical Hospital №1"; Infectious Department
🇺🇦Vinnytsia, KIEV Governorate, Ukraine
MI Dnipropetrovsk City Clinical Hospital #21 n.a. Prof. Popkova of DRC; The First Department
🇺🇦Dnipro, Podolia Governorate, Ukraine
Kyiv Oleksandrivska Clinical Hospital; Infectious Box Department #2
🇺🇦Kyiv, Katerynoslav Governorate, Ukraine
Ternopil City Municipal Emergency Hospital; Infectious Department
🇺🇦Ternopil, KIEV Governorate, Ukraine
NorthShore University HealthSystem
🇺🇸Evanston, Illinois, United States
University of Chicago; Oncology Dept
🇺🇸Chicago, Illinois, United States
Mercury Street Medical Group
🇺🇸Butte, Montana, United States
Rambam Health Corporation; Oncology Institute
🇮🇱Rambam, Israel
Beijing Youan Hospital, Capital Medical University; Center for Infectious Diseases
🇨🇳Beijing City, China
Fakultni nemocnice Brno; Interni hematologicka a onkologicka klinika
🇨🇿Brno, Czechia
Klinikum Mannheim GmbH Universitätsklinikum
🇩🇪Mannheim, Germany
Klinikum der Universität Regensburg
🇩🇪Regensburg, Germany
Detroit Receiving Hospital
🇺🇸Detroit, Michigan, United States
Creighton University Medical Center
🇺🇸Omaha, Nebraska, United States
Froedtert and The Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Centro de Estudos Clinicos do Interior Paulista
🇧🇷JAU, SP, Brazil
Atlanta Institute For Medical Research, Inc; DeKalb Medical Pharmacy
🇺🇸Decatur, Georgia, United States
Denver Health Medical Center
🇺🇸Denver, Colorado, United States
Torrance Memorial Medical Center
🇺🇸Torrance, California, United States
Salem Veterans Affairs Medical Center - NAVREF; Pharmacy
🇺🇸Salem, Virginia, United States
Temple University Hospital ; Lung Center
🇺🇸Philadelphia, Pennsylvania, United States
New York-Presbyterian Brooklyn Methodist Hospital; Department of Emergency Medicine
🇺🇸Brooklyn, New York, United States
Royal Brisbane & Womens Hospital; Pharmacy Department
🇦🇺Herston, Queensland, Australia
Royal Children's Hospital Melbourne - PIN
🇦🇺Parkville, Victoria, Australia
Santa Casa de Misericordia; de Belo Horizonte
🇧🇷Belo Horizonte, MG, Brazil
Hospital Sao Vicente de Paulo
🇧🇷Passo Fundo, RS, Brazil
Multiprofile Hospital For Active Treatment - Dr. Bratan Shukerov AD; Pharmacy
🇧🇬Smolyan, Bulgaria
Fifth Multiprofile Hospital for Active Treatment - Sofia EAD; Pharmacy
🇧🇬Sofia, Bulgaria
First Multiprofile Hospital for Active Treatment - Sofia EAD
🇧🇬Sofia, Bulgaria
National Multiprofile Transport Hospital Tzar Boris Ill; Clinic of Internal Diseases
🇧🇬Sofia, Bulgaria
Multiprofile District Hospital for Active Treatment Dr. Stefan Cherkezov AD; Pharmacy
🇧🇬Veliko Tarnovo, Bulgaria
Foothills Medical Centre
🇨🇦Calgary, Alberta, Canada
University of Alberta Hospital
🇨🇦Edmonton, Alberta, Canada
Toronto East General Hospital; Main Pharmacy G Wing Basement
🇨🇦East York, Ontario, Canada
London Health Sciences Center; Pharmacy Dept.
🇨🇦London, Ontario, Canada
Institut Universitaire de Cardiologie et de Pneumologie
🇨🇦Quebec, Canada
West China Hospital, Sichuan University
🇨🇳Chengdu, China
China-Japan Friendship Hospital
🇨🇳Beijing, China
Beijing Ditan Hospital Capital Medical University
🇨🇳Beijing, China
The First Affiliated Hospital of Guangzhou Medical University
🇨🇳Guangzhou, China
The First Affiliated Hospital of College of Medicine, Zhejiang University
🇨🇳Hangzhou, China
The 1st Affiliated Hospital of Nanchang Unversity
🇨🇳Nanchang, China
Shanghai Jiao Tong University School of Medicine (SJTUSM) - Ruijin Hospital (GuangCi Hospital)
🇨🇳Shanghai, China
Zhongshan Hospital Fudan University
🇨🇳Shanghai, China
Shanghai Public Health Clinical Center
🇨🇳Shanghai, China
Kuopion Yliopistollinen Sairaala; Silmätaudit
🇫🇮Kuopio, Finland
Nemocnice Kyjov, prispevkova organizace
🇨🇿Kyjov, Czechia
Oulun Yliopistollinen Sairaala; Teho-osasto
🇫🇮Oulu, Finland
East Tallinn Central Hospital
🇪🇪Tallinn, Estonia
Turku University Hospital
🇫🇮Turku, Finland
Centre Hospitalier Victor Dupouy
🇫🇷Argenteuil, France
Hôpital Universitaire Dupuytren
🇫🇷Limoges, France
CHRU Dijon Complexe Du Bocage
🇫🇷Dijon, France
Centre Hospitalier Departemental de Vendee
🇫🇷La Roche Sur Yon, France
CHRU Nantes
🇫🇷Nantes, France
CHU de Nîmes - Hôpital Carémeau
🇫🇷Nimes, France
Nouvel Hopital Civil - CHU Strasbourg
🇫🇷Strasbourg, France
Hopital de La Source
🇫🇷Orleans, France
CHRU Bretonneau
🇫🇷Tours, France
Universitätsklinikum Carl Gustav Carus an der TU Dresden
🇩🇪Dresden, Germany
Groupe Hospitalier Pitie Salpetriere; Service De Pneumologie
🇫🇷Paris, France
St. Josefskrankenhaus - Freiburg; Klinik fur Pneumologieund Beatmungsmedizin
🇩🇪Freiburg im Breisgau, Germany
Krankenhaus Donaustauf der LVA Niederbayern Oberpfalz
🇩🇪Donaustauf, Germany
Uniklinik Koln; Klinik I fur Innere Medizin
🇩🇪Köln, Germany
Universitatsklinikum Schleswig-Holstein; Klinik fuer Innere Medizin I
🇩🇪Lubeck, Germany
Medizinische Hochschule Hannover
🇩🇪Hannover, Germany
Universitatsklinikum Tubingen
🇩🇪Tübingen, Germany
Prince of Wales Hospital
🇭🇰Shatin, New Territories, Hong Kong
Galilee Medical Center
🇮🇱Nahariya, Israel
Edith Wolfson Medical Center
🇮🇱Holon, Israel
Chaim Sheba Medical Center; Allergy and Clinical Immunology Unit
🇮🇱Ramat Gan, Israel
Tel Aviv Sourasky Medical Center; Pharmacy
🇮🇱Tel Aviv, Israel
ZIV Medical Center; Department Of Internal Medicine A
🇮🇱Safed, Israel
Fukuoka Shin Mizumaki Hospital
🇯🇵Fukuoka, Japan
Baruch Padeh Poria Medical Center; Pharmacy
🇮🇱Tiberias, Israel
Fujita General Hospital
🇯🇵Dategun Kunimimachi, Japan
Rinku General Medical Center
🇯🇵Izumisano, Japan
Shin Komonji Hospital
🇯🇵Fukuoka, Japan
Fukuoka Wajiro Hospital
🇯🇵Fukuoka, Japan
National Hospital Organization Minami Kyoto Hospital
🇯🇵Joyo, Japan
National Hospital Organization Kanazawa Medical Center
🇯🇵Kanazawa, Japan
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Queen Mary Hospital
🇭🇰Hong Kong, Hong Kong
Princess Margaret Hospital
🇭🇰Hong Kong, Hong Kong