A Study of MHAA4549A in Combination With Oseltamivir Versus Oseltamivir in Participants With Severe Influenza A Infection
- Registration Number
- NCT02293863
- Lead Sponsor
- Genentech, Inc.
- Brief Summary
This is a randomized, double-blind, placebo-controlled study that will investigate the safety and clinical activity of a single intravenous (IV) dose of MHAA4549A in adult participants hospitalized with severe influenza A in combination with oseltamivir versus a comparator arm of placebo with oseltamivir.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 168
- Diagnosis of influenza A where a Sponsor-approved influenza test is used as an aid in diagnosis. A Sponsor-approved influenza test includes: Influenza antigen test or Influenza polymerase chain reaction (PCR) test
- One of the following markers of severity within 24 hours of admission: requirement for O2 supplementation to maintain SpO2 greater than (>) 92 %; or requirement for Positive Pressure Ventilation (PPV)
- A negative urine or serum pregnancy test for women of childbearing potential within 2 days prior to study treatment
- Participants of reproductive potential must agree to use acceptable contraceptive measures as per the protocol as a minimum, and local guidelines, if more stringent
- Pregnant or lactating women, or women who intend to become pregnant during the study
- Hypersensitivity to monoclonal antibodies or any constituents (sodium succinate, sucrose, polysorbate 20) of study drug
- Hypersensitivity to the active substance or to any excipients of oseltamivir
- Investigational therapy within the 30 days prior to study treatment
- Received prior therapy with any anti-influenza monoclonal antibody therapy (including MHAA4549A) within 8 months prior to study treatment
- Current treatment (within 7 days of dosing) with probenecid, amantadine or rimantidine
- Participants who have taken more than a total of 6 doses (3 doses for peramivir) of anti-influenza therapy (e.g., oseltamivir, zanamivir, laninamivir, peramivir) in the period from onset of symptoms and prior to study treatment
- Admission >48 hours prior to study treatment
- Onset of influenza symptoms (including fever, chills, malaise, dry cough, loss of appetite, myalgias, coryza, or nausea) >5 days prior to study treatment
- Positive influenza B or influenza A + B infection within 2 weeks prior to study treatment
- High probability of mortality in the next 48 hours as determined by the investigator
- Participants requiring home or baseline oxygenation therapy
- Participants with history of chronic lung disease with a documented SpO2 less than (<) 95% off oxygen
- Participants on chronic dose of corticosteroids exceeding 10 milligrams per day (mg/day) of prednisone or equivalent steroid dose for duration of greater than 14 days within 30 days of entry into study
- Participants with the following significant immune suppression: bone marrow or solid organ transplant in the previous 12 months; cancer chemotherapy in the previous 12 months, HIV infection with most recent Cluster of Differentiation 4 (CD4) <200 cells per milliliter (cells/mL), or other significant immune suppression as determined by the investigator in discussion with the Sponsor Medical Monitor
- Participants on extracorporeal membrane oxygenation (ECMO) at time of randomization
- Any disease or condition that would, in the opinion of the site investigator or Sponsor, place the participant at an unacceptable risk of injury or render the participant unable to meet the requirements of the protocol
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description A: MHAA4549A 3600 mg + Oseltamivir MHAA4549A Participants will receive a single low IV dose of MHAA4549A on Day 1 and standard oseltamivir therapy for minimum of 5 days. C: Placebo + Oseltamivir Placebo Participants will receive a single IV dose of placebo matched to MHAA4549A on Day 1 and standard oseltamivir therapy (75 or 150 mg BID) for minimum of 5 days. A: MHAA4549A 3600 mg + Oseltamivir Oseltamivir Participants will receive a single low IV dose of MHAA4549A on Day 1 and standard oseltamivir therapy for minimum of 5 days. B: MHAA4549A 8400 mg + Oseltamivir Oseltamivir Participants will receive a single high IV dose of MHAA4549A on Day 1 and standard oseltamivir therapy for minimum of 5 days. C: Placebo + Oseltamivir Oseltamivir Participants will receive a single IV dose of placebo matched to MHAA4549A on Day 1 and standard oseltamivir therapy (75 or 150 mg BID) for minimum of 5 days. B: MHAA4549A 8400 mg + Oseltamivir MHAA4549A Participants will receive a single high IV dose of MHAA4549A on Day 1 and standard oseltamivir therapy for minimum of 5 days.
- Primary Outcome Measures
Name Time Method Percentage of Participants With Adverse Events From randomization up to 60 days An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.
Number of Participants With Anti-Therapeutic Antibodies (ATA) to MHAA4549A During and Following Administration of MHAA4549A From randomization up to 60 days Reported are the number of participants positive for ATAs at baseline, the number of participants with treatment-induced ATAs and the number of participants with treatment-enhanced ATAs.
Time to Normalization of Respiratory Function From randomization up to 60 days The time to normalization of respiratory function was defined as the time to removal of the participant from oxygen (O2) supplementation in order to maintain a blood oxygen saturation level (SpO2) equal to or greater than 95% as measured by pulse oximetry.
- Secondary Outcome Measures
Name Time Method Percentage of Participants by Clinical Status Using a Categorical Ordinal Outcome Days 1-7, 14 and 30 The clinical status of participants was defined by five mutually exclusive categories: 1. Death; 2. In the Intensive Care Unit (ICU); 3. Non-ICU hospitalization, requiring supplemental oxygen (O2); 4. Non-ICU hospitalization, not requiring supplemental oxygen (O2); 5. Not hospitalized.
Percentage of Participants With Clinical Failure 24 hours after end of infusion (infusion duration = approximately 120 minutes) up to Day 60 Clinical failure after 24 hours post-infusion of study drug was defined as progression to increased O2 requirement defined by an increase in oxygen supplementation from low flow oxygen (i.e., 2-6 liters per minute \[L/min\]) to high flow oxygen (i.e., \> 6 L/min) or from oxygen supplementation alone to any positive pressure ventilation (PPV) or extracorporeal membrane oxygenation (ECMO), progression to ICU, prolonged ventilation or O2 support defined by \> 2 weeks, or death.
Percentage of Participants With Clinical Resolution of Abnormal Vital Signs From randomization up to 60 days Description: Clinical resolution of abnormal vital signs was defined as meeting three out of five of the following criteria: 1. SpO2 ≥ 95% without supplemental O2; 2. Respiratory rate \< 24 breaths per minute without supplemental O2; 3. Core temperature \< 37.2 Celsius (C) immediately prior to receipt of any antipyretic drug, and at least 6-8 hours from the last dose of antipyretic or core temperature \> 36 C in participants who are initially hypothermic; 4. Heart rate (HR) \< 100 beats/minute; 5. Systolic blood pressure (SBP) \>90 mmHg. Reported here is the percentage of participants who had clinical resolution of at least three out of five abnormal vital signs by the end of study.
Percentage of Participants Who Died Due to Any Cause Days 14, 30 and 60 Area Under Viral Load-Time Curve (AUEC ) of Influenza A Virus Immediately prior to MHAA4549A infusion and oseltamivir dosing on Day 1, immediately prior to oseltamivir dosing on Days 2 to 10, Days 14, 20, 25, 30, on day of discharge from hospital (up to Day 60), and at study completion (Day 60) Influenza A viral load was measured by quantitative polymerase chain reaction (qPCR) in nasopharyngeal samples at multiple time points during the study. AUEC is the area under the viral load-time curve expressed as log10 (viral particles/milliliter x hour) = log10 (vp/mL x hour).
Peak Influenza A Viral Load Immediately prior to MHAA4549A infusion and oseltamivir dosing on Day 1, immediately prior to oseltamivir dosing on Days 2 to 10, Days 14, 20, 25, 30, on day of discharge from hospital (up to Day 60), and at study completion (Day 60) Influenza A viral load was measured by qPCR in nasopharyngeal samples at multiple time points during the study. Reported here is the peak Influenza A viral load expressed as log10 vp/mL.
Duration of Hospitalization From randomization up to 60 days Duration of Viral Shedding Immediately prior to MHAA4549A infusion and oseltamivir dosing on Day 1, immediately prior to oseltamivir dosing on Days 2 to 10, Days 14, 20, 25, 30, on day of discharge from hospital (up to Day 60), and at study completion (Day 60) Influenza A viral load was measured by qPCR in nasopharyngeal samples at multiple time points during the study. Reported here is the duration of viral shedding.
Duration of Intensive Care Unit (ICU) Stay From randomization up to 60 days Percentage of Participants Using Antibiotics for Respiratory Infections From randomization up to 60 days Percentage of Participants With Secondary Complications of Influenza From randomization up to 60 days The following were considered secondary complications of influenza: pneumonia, including hospital-acquired pneumonia (HAP) and ventilation-acquired pneumonia (VAP), exacerbations of chronic lung disease, myocarditis, acute respiratory distress syndrome (ARDS), otitis media, or other related complications.
Percentage of Participants Readmitted to Hospital Due to Any Cause Days 30 and 60 Duration of Ventilation From randomization up to 60 days Area Under Serum Concentration-Time Curve From Time 0 to Infinity (AUC ) of MHAA4549A 30 minutes (min) before & 60 min after end of MHAA4549A infusion (infusion duration = 120 min) on Day 1; immediately prior to oseltamivir dose on Days 2, 3, 5, 7; on Days 14, 30; on day of discharge (up to Day 60); at study completion (Day 60) AUC0-inf is reported as day\*microgram/milliliter (day\*mcg/mL).
Maximum Serum Concentration (Cmax ) of MHAA4549A 30 min before & 60 min after end of MHAA4549A infusion (infusion duration = 120 min) on Day 1; immediately prior to oseltamivir dose on Days 2, 3, 5, 7; on Days 14, 30; on day of discharge (up to Day 60); at study completion (Day 60) Elimination Half-Life (Terminal t1/2) of MHAA4549A 30 min before & 60 min after end of MHAA4549A infusion (infusion duration = 120 min) on Day 1; immediately prior to oseltamivir dose on Days 2, 3, 5, 7; on Days 14, 30; on day of discharge (up to Day 60); at study completion (Day 60) Observed Clearance (CL-obs) of MHAA4549A 30 min before & 60 min after end of MHAA4549A infusion (infusion duration = 120 min) on Day 1; immediately prior to oseltamivir dose on Days 2, 3, 5, 7; on Days 14, 30; on day of discharge (up to Day 60); at study completion (Day 60) Observed Steady State Volume of Distribution (Vss_obs) of MHAA4549A 30 min before & 60 min after end of MHAA4549A infusion (infusion duration = 120 min) on Day 1; immediately prior to oseltamivir dose on Days 2, 3, 5, 7; on Days 14, 30; on day of discharge (up to Day 60); at study completion (Day 60)
Trial Locations
- Locations (171)
CEPREP; Hospital Universitario
🇲🇽Monterrey, Mexico
Oddział Anestezjologii i Intensywnej Terapii Wojewódzki Specjalistyczny Szpital im dr Wł Biegańsk
🇵🇱Łódź, Poland
MHAT "Dr. Tota Venkova"- Gabrovo
🇧🇬Gabrovo, Bulgaria
Hospital Edmundo Vasconcelos
🇧🇷Vila Clementino, SP, Brazil
Santa Casa de Misericordia; de Belo Horizonte
🇧🇷Belo Horizonte, MG, Brazil
CHRU Lille
🇫🇷Lille, France
5th Multifunctional Hospital for Active treatment
🇧🇬Sofia, Bulgaria
FUNFARME
🇧🇷Sao Jose do Rio Preto, SP, Brazil
Hospital Sao Vicente de Paulo
🇧🇷Passo Fundo, RS, Brazil
PUC Campinas
🇧🇷Campinas, SP, Brazil
CHU St Pierre (St Pierre)
🇧🇪Brussels, Belgium
MHAT Lyulin EAD, Department of internal diseases
🇧🇬Sofia, Bulgaria
University Multiprofile Hospital for Active Treatment "St. George"
🇧🇬Plovdiv, Bulgaria
University College London Hospitals NHS Foundation Trust - University College Hospital
🇬🇧London, United Kingdom
Kyiv City Clinical Hospital #4
🇺🇦Kyiv, Ukraine
Municipal Institution City Clinical Infectious Diseases Hospital
🇺🇦Odesa, Ukraine
Chang Gung Medical Foundation Linkou Branch
🇨🇳Taoyuan City, Taiwan
Kyiv City Clinical Hospital #9
🇺🇦Kyiv, Ukraine
Ziv Medical Center
🇮🇱Zefat, Israel
Poltava Regional Clinical Infectious Hospital
🇺🇦Poltava, Ukraine
King College Hospital NHS Foundation Trust
🇬🇧London, United Kingdom
Jeroen Bosch Ziekenhuis
🇳🇱'S Hertogenbosch, Netherlands
Queen Elizabeth University Hospital
🇬🇧Glasgow, United Kingdom
Heart of England NHS Trust
🇬🇧Birmingham, United Kingdom
Leeds General Infirmary, Anaesthetic Department, D Floor
🇬🇧Leeds, United Kingdom
Southampton University Hospitals NHS Trust
🇬🇧Southampton, United Kingdom
Queen Elizabeth Hospital
🇬🇧Birmingham, United Kingdom
Municipal Institution Central City Hospital #1 City of Zhytomyr
🇺🇦Zhytomyr, Ukraine
CHU UCL Mont-Godinne
🇧🇪Mont-godinne, Belgium
Ospedale San Raffaele - Milano
🇮🇹Milano, Lombardia, Italy
Taunton and Somerset NHS Foundation Trust Musgrove Park Hospital
🇬🇧Taunton, United Kingdom
Centre de santé et de services sociaux de Trois-Rivières
🇨🇦Trois-Rivieres, Quebec, Canada
Csolnoky Ferenc Kórház
🇭🇺Veszprém, Hungary
Zala County Hospital ICU
🇭🇺Zalaegerszeg, Hungary
Jávorszky Ödön Hospital
🇭🇺Vác, Hungary
SHATPPD Dr. Dimitar Gramatikov, Ruse Ltd.
🇧🇬Ruse, Bulgaria
UZ Leuven Gasthuisberg
🇧🇪Leuven, Belgium
Hospital Alemao Oswaldo Cruz; Oncologia
🇧🇷Sao Paulo, SP, Brazil
MHAT TOKUDA SOFIA/ICU-Intensive Care Unit
🇧🇬Sofia, Bulgaria
Military Medical Academy- MHAT
🇧🇬Sofia, Bulgaria
Multiprofile Hospital for Active Treatment AKTA-MEDIKA EOOD
🇧🇬Sevlievo, Bulgaria
MBAL St Marina Dep Pulmonology, ICU
🇧🇬Varna, Bulgaria
Peter Lougheed Centre
🇨🇦Calgary, Alberta, Canada
Alberta Health Services
🇨🇦Calgary, Alberta, Canada
University Multiprofile Hospital for Active Treatment and Emergency Medicine N. I. Pirogov EAD
🇧🇬Sofia, Bulgaria
Multiprofile District Hospital for Active Treatment Dr. Stefan Cherkezov AD
🇧🇬Veliko Tarnovo, Bulgaria
Foothills Medical Centre
🇨🇦Calgary, Alberta, Canada
Rockyview General Hospital
🇨🇦Calgary, Alberta, Canada
The Ottawa Hospital - Civic Campus
🇨🇦Ottawa, Ontario, Canada
Royal Columbian Hospital
🇨🇦New Westminster, British Columbia, Canada
St. Paul's Hospital, Providence Health Care
🇨🇦Vancouver, British Columbia, Canada
Victoria General Hospital
🇨🇦Victora, British Columbia, Canada
Moncton Hospital
🇨🇦Moncton, New Brunswick, Canada
Ottawa Hospital Research Institute
🇨🇦Ottawa, Ontario, Canada
Lakeridge Health
🇨🇦Oshawa, Ontario, Canada
LHSC - University Hospital; Research Pharmacy
🇨🇦London, Ontario, Canada
Toronto East General
🇨🇦Toronto, Ontario, Canada
Toronto Western Hospital
🇨🇦Toronto, Ontario, Canada
Centre Hospitalier de la Universite Laval
🇨🇦Quebec City, Quebec, Canada
Pavillion Chul-Chuq
🇨🇦Sainte-foy, Quebec, Canada
Hospital Dr. Hernan Henriquez Aravena
🇨🇱Temuco, Chile
Clinica Renaca
🇨🇱Vina del Mar, Chile
Anesthesia and Intensive Care Dept., Regional Hospital Liberec
🇨🇿Liberec, Czechia
Fakultni nemocnice Hradec Kralove
🇨🇿Hradec Kralove, Czechia
The University Hospital Brno
🇨🇿Brno, Czechia
Archet 1 university Hospital
🇫🇷Nice, France
Fakultni nemocnice Kralovske Vinohrady, Klinika anesteziologie a resuscitace
🇨🇿Praha 10, Czechia
University hospital Ostrava, Clinic of infectious medicine
🇨🇿Ostrava, Czechia
Service de Réanimation médicale - Bocage Central
🇫🇷Dijon, France
CH Victor Dupouy
🇫🇷Argenteuil, France
Centre Hospitalier Universitaire de Clermont Ferrand
🇫🇷Clermont-ferrand, France
HOPITAL COCHIN university hospital
🇫🇷Paris, France
APHP Raymond Poincare
🇫🇷Garches, France
CHRU Nancy
🇫🇷Nancy, France
Réanimation Polyvalente, CHU Limoges
🇫🇷Limoges, France
Réanimation médicale NHC
🇫🇷Strasbourg, France
Hopital Universitaire Hautepierre
🇫🇷Strasbourg, France
Service de réanimation médicale, Hôpital Bretonneau
🇫🇷Tours, France
Universitätsklinikum Frankfurt Goethe Universität
🇩🇪Frankfurt, Germany
Universitätsklinikum Heidelberg
🇩🇪Heidelberg, Germany
Uniklinikum Mainz
🇩🇪Mainz, Germany
Uniklinik Tübingen
🇩🇪Tuebingen, Germany
Uniklinik Köln, Medizinischen Klinik I
🇩🇪Koeln, Germany
Haemek Medical Center
🇮🇱Afula, Israel
Soroka University Medical Centre
🇮🇱Beer-Sheva, Israel
Wolfson Medical Center
🇮🇱Holon, Israel
Nazareth EMMS Hospital
🇮🇱Nazareth, Israel
Galilee Medical Center
🇮🇱Nahariya, Israel
Kaplan Medical Center
🇮🇱Rehovot, Israel
Tel-Aviv Sourasky Medical Center
🇮🇱Tel Aviv, Israel
Chaim Sheba Medical Center
🇮🇱Tel Hashomer, Israel
Hadasit Medical Research Services and Development Ltd
🇮🇱Jerusalem, Israel
Rabin Medical Center
🇮🇱Petah Tikva, Israel
University Hospital Modena, Intensive Care Unit
🇮🇹Modena, Emilia-Romagna, Italy
University Division of Infective and Tropical Diseases, University of Brescia, Italy
🇮🇹Brescia, Basilicata, Italy
Asst Di Cremona
🇮🇹Cremona, Lombardia, Italy
National Institute for Infectious Diseases "L. Spallanzani"
🇮🇹Rome, Lazio, Italy
A.O.U. S. Giovanni di Dio e Ruggi d'Aragona
🇮🇹Salerno, Sardegna, Italy
Pusan National University Hospital
🇰🇷Busan, Korea, Republic of
Gachon University Gil Hospital
🇰🇷Incheon, Korea, Republic of
Wonju Severance Christian Hospital
🇰🇷Wonju, Korea, Republic of
Korea University Anam Hospital
🇰🇷Seoul, Korea, Republic of
Instituto Nacional de Ciencias; Medicas y Nutricion; Salvador Zubiran
🇲🇽Mexico, Distrito Federal, Mexico
Hallym university Kangnam Sacred Heart Hospital; Infectious devision
🇰🇷Seoul, Korea, Republic of
Hospital Civil de Guadalajara Fray Antonio Alcalde
🇲🇽Guadalajara, Mexico
Centro de Especialidades Medicas Del Estado de Veracruz Dr Rafael Lucio
🇲🇽Xalapa-enriquez, Mexico
Hospital General de Tijuana
🇲🇽Tijuana, Mexico
Gelre Ziekenhuizen Apeldoorn; Hospitals Pharmacy
🇳🇱Apeldoorn, Netherlands
UMC Radboud Nijmegen
🇳🇱Nijmegen, Netherlands
Ikazia Hospital
🇳🇱Rotterdam, Netherlands
LUMC
🇳🇱Leiden, Netherlands
Erasmus Medical Centre; Department of Virology L-359
🇳🇱Rotterdam, Netherlands
UMCU
🇳🇱Utrecht, Netherlands
Isala
🇳🇱Zwolle, Netherlands
Auckland City Hospital
🇳🇿Auckland, New Zealand
Hospital Regional del Cusco
🇵🇪Cusco, Peru
Hospital Guillermo Almenara Irigoyen Hospital Guillermo Almenara Irigoyen Hospital Guillermo Almen
🇵🇪La Victoria, Peru
Hospital Nacional Adolfo Guevara Velasco
🇵🇪Cuzco, Peru
Christchurch Hospital
🇳🇿Christchurch, New Zealand
Tauranga Hospital
🇳🇿Tauranga, New Zealand
Clinica Internacional Sede Lima
🇵🇪LIma, Peru
Hospital Central Fuerza; Aerea del Peru
🇵🇪Lima, Peru
Hospital Maria Auxiliadora
🇵🇪Lima, Peru
Hospital Nacional; Arzobispo Loayza
🇵🇪LIma, Peru
Clinica San Borja
🇵🇪Lima, Peru
Clínica San Gabriel
🇵🇪Lima, Peru
Icu Spsk - 2
🇵🇱Szczecin, Poland
Hospital de la Amistad Peru Corea II-2 Santa Rosa
🇵🇪Piura, Peru
Clinica Divino Nino Jesus; Orden de Malta
🇵🇪San Juan de Miraflores, Peru
Clinica Peruana Americana
🇵🇪Trujillo, Peru
Oddział Anestezjologii i Intensywnej Terapii;Wojewódzki Szpital Zespolony im. L. Rydygiera
🇵🇱Toruń, Poland
Municipal Clinical Hospital #8
🇷🇺Chelyabinsk, Russian Federation
Municipal Healthcare Institution "City Hospital №2"
🇷🇺Engels, Russian Federation
Medical Military Academy n.a S.M.Kirov
🇷🇺St.Petersburg, Russian Federation
Milpark Hospital
🇿🇦Parktown West, South Africa
Paciific state medical university
🇷🇺Vladivostok, Russian Federation
Emmed Research
🇿🇦Pretoria, South Africa
Hospital Clinic
🇪🇸Barcelona, Cantabria, Spain
Hospital de Mataro
🇪🇸Mataro, Cantabria, Spain
Clinical Projects Research
🇿🇦Worcester, South Africa
Mutua de Terrassa
🇪🇸Terrassa, Barcelona, Spain
Hospital Universitario Marques de Valdecilla
🇪🇸Santander, Cantabria, Spain
Hospital Universitario Son Espases
🇪🇸Palma de Mallorca, Islas Baleares, Spain
Hospital del Mar
🇪🇸Barcelona, Spain
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Spain
Bellvitge University Hospital
🇪🇸Barcelona, Spain
Hosp. Clinico San Carlos
🇪🇸Madrid, Spain
Hospital Universitario San Cecilio
🇪🇸Granada, Spain
Servicio de Medicina Intensiva Hospital Universitario la Fe
🇪🇸Valencia, Spain
Hospital Univ. de Getafe.Servicio de Neurologia
🇪🇸Madrid, Spain
Joan XXIII University Hospital
🇪🇸Tarragona, Spain
Sahlgrenska Universitetssjukhuset
🇸🇪Goteborg, Sweden
Uppsala University Hospital, Department of Infectious Diseases
🇸🇪Göteborg, Sweden
Norrland Universitetssjukhus
🇸🇪Umeå, Sweden
Skånes Universitetssjukhus
🇸🇪Mamö, Sweden
Kaohsiung Medical University Hospital, Cancer Center
🇨🇳Kaohsiung, Taiwan
Wanfang Hospital
🇨🇳Taipei, Taiwan
Far East Memorial Hospital
🇨🇳New Taipei, Taiwan
University Hospitals of North Midlands NHS Trust-Royal Stoke University Hospital
🇬🇧Stoke-On-Trent, United Kingdom
CHD Vendée
🇫🇷La Roche Sur Yon, France
University Health Network
🇨🇦Toronto, Ontario, Canada
Pest Megyei Flor Ferenc Korhaz
🇭🇺Kistarcsa, Hungary
Clinic of Infectious Diseases
🇮🇹Bologna, Emilia-Romagna, Italy
Korea University Guro Hospital
🇰🇷Seoul, Korea, Republic of
Yonsei University Health System/Severance Hospital
🇰🇷Seoul, Korea, Republic of
Hospital Nacional Hipolito; Unanue
🇵🇪Lima, Peru
Royal Jubilee Hospital Victoria general Hospital
🇨🇦Victoria, British Columbia, Canada
Hospital Civil de Guadalajara Dr Juan I Menchaca
🇲🇽Guadalajara, Mexico
Wojewodzki Szpital Specjalistyczny
🇵🇱Lublin, Poland
Hospital Erasme; Neurologie
🇧🇪Bruxelles, Belgium
University of Hong Kong
🇭🇰Hong Kong, Hong Kong