A Study to Evaluate the Efficacy and Safety of Pimodivir in Combination With the Standard-of-Care Treatment in Adolescent, Adult, and Elderly Hospitalized Participants With Influenza A Infection
- Conditions
- Influenza A
- Interventions
- Registration Number
- NCT03376321
- Lead Sponsor
- Janssen Research & Development, LLC
- Brief Summary
The purpose of this study is to evaluate the clinical and virologic benefit of pimodivir in combination with Standard-of-Care (SOC) treatment compared to placebo in combination with SOC treatment.
- Detailed Description
This double-blind (neither researchers nor participants know what treatment participant is receiving) study will evaluate efficacy/safety of pimodivir in combination with SOC treatment versus placebo in combination with SOC treatment in adolescent, adult, and elderly hospitalized participants with influenza A infection. The study will be conducted in 3 phases: screening phase, double-blind treatment period of 5 days (with the possibility to extend treatment period by 5 days for participants who will enter an optional double-blind extension treatment arm), and post treatment follow-up period of 23 days. Study evaluations will include efficacy, pharmacokinetic, biomarkers, safety and tolerability. The duration of participation in study for each participant is 28 days, except for participants receiving extended treatment, for whom study duration will be up to 33 days.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 334
- Tested positive for influenza A infection after the onset of symptoms using a polymerase chain reaction (PCR)-based or other rapid molecular diagnostic assay
- Requires hospitalization to treat influenza infection and/or to treat complications of influenza infection (for example, radiological signs of lower respiratory tract disease, septic shock, central nervous system [CNS] involvement, myositis, rhabdomyolysis, acute exacerbation of chronic kidney disease, severe dehydration, myocarditis, pericarditis, ischemic heart disease, exacerbation of underlying chronic pulmonary disease, including asthma, chronic obstructive pulmonary disease [COPD], decompensation of previously controlled diabetes mellitus), including participants admitted to the Intensive Care Unit (ICU)
- Enrollment and initiation of study drug treatment less than or equal to (<=)96 hours after onset of influenza symptoms
- Being on invasive mechanical ventilation or having a peripheral capillary oxygen saturation (SpO2) less than (<)94 percent (%) on room air during screening. Participants with known pre-influenza SpO2 <94% must have an SpO2 decline greater than or equal to (>=)3% from pre-influenza SpO2 during screening
- Having a screening/baseline National Early Warning Score 2 (NEWS2) of >=4
- Received more than 3 doses of influenza antiviral medication (for example, oseltamivir [OST] or zanamivir), or any dose of ribavarin (RBV) within 2 weeks, prior to first study drug intake. Received intravenous (IV) peramivir more than one day prior to screening
- Unstable angina pectoris or myocardial infarction within 30 days prior to screening (inclusive)
- Presence of clinically significant heart arrhythmias, uncontrolled, unstable atrial arrhythmia, or sustained ventricular arrhythmia, or risk factors for Torsade de Pointes syndrome
- Known severe hepatic impairment (Child Pugh C cirrhosis) or chronic hepatitis C infection undergoing hepatitis C antiviral therapy
- Severely immunocompromised in the opinion of the investigator (for example, known cluster of differentiation 4 plus [CD4+] count <200 cells per cubic millimeter [cells/mm^3], absolute neutrophil count <750/mm^3, first course of chemotherapy completed within 2 weeks prior to screening, history of stem cell transplant within 1 year prior to screening, any history of a lung transplant)
- Known allergies, hypersensitivity, or intolerance to pimodivir or its excipients
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Treatment Arm 1 (pimodivir + Standard-of-Care [SOC] treatment) Pimodivir 600 mg Participants will receive pimodivir 600 milligram (mg) orally twice daily for 5 days (on Days 1 through 5; for participants who will receive only 1 dose of pimodivir on Day 1 \[evening\], dosing will continue until the morning of Day 6) along with SOC treatment. Participants who meet all treatment extension criteria as defined in the protocol may receive an additional 5 day course of same treatment as received at study start. The SOC treatment is determined by investigator based on local practice, may include influenza antivirals and/or supportive care only. The choice to use influenza antivirals as part of SOC should be started no later than the day when participants initially receive pimodivir. An influenza antiviral as part of SOC cannot be changed (example, switching one influenza antiviral for another) during either treatment period or extension phase, with the exception that an influenza antiviral may be discontinued in case of suspected adverse event (AE). Treatment Arm 1 (pimodivir + Standard-of-Care [SOC] treatment) SOC Treatment Participants will receive pimodivir 600 milligram (mg) orally twice daily for 5 days (on Days 1 through 5; for participants who will receive only 1 dose of pimodivir on Day 1 \[evening\], dosing will continue until the morning of Day 6) along with SOC treatment. Participants who meet all treatment extension criteria as defined in the protocol may receive an additional 5 day course of same treatment as received at study start. The SOC treatment is determined by investigator based on local practice, may include influenza antivirals and/or supportive care only. The choice to use influenza antivirals as part of SOC should be started no later than the day when participants initially receive pimodivir. An influenza antiviral as part of SOC cannot be changed (example, switching one influenza antiviral for another) during either treatment period or extension phase, with the exception that an influenza antiviral may be discontinued in case of suspected adverse event (AE). Treatment Arm 2 (placebo + SOC treatment) Placebo Participants will receive placebo matching to pimodivir orally twice daily for 5 days (on Days 1 through 5; for participants who will receive only 1 dose of placebo on Day 1 \[evening\], dosing will continue until morning of Day 6) along with SOC treatment. Participants who meet all treatment extension criteria as defined in protocol may receive an additional 5 day course of same treatment as received at study start. The SOC treatment determined by investigator based on local practice, may include influenza antivirals and/or supportive care only. The choice to use influenza antivirals as part of the SOC should be made before randomization. The influenza antiviral should be started no later than day of first study drug intake. An influenza antiviral as part of the SOC cannot be changed (for example, switching one influenza antiviral for another) during either treatment period/extension phase, with the exception that an influenza antiviral may be discontinued in case of a suspected AE. Treatment Arm 2 (placebo + SOC treatment) SOC Treatment Participants will receive placebo matching to pimodivir orally twice daily for 5 days (on Days 1 through 5; for participants who will receive only 1 dose of placebo on Day 1 \[evening\], dosing will continue until morning of Day 6) along with SOC treatment. Participants who meet all treatment extension criteria as defined in protocol may receive an additional 5 day course of same treatment as received at study start. The SOC treatment determined by investigator based on local practice, may include influenza antivirals and/or supportive care only. The choice to use influenza antivirals as part of the SOC should be made before randomization. The influenza antiviral should be started no later than day of first study drug intake. An influenza antiviral as part of the SOC cannot be changed (for example, switching one influenza antiviral for another) during either treatment period/extension phase, with the exception that an influenza antiviral may be discontinued in case of a suspected AE.
- Primary Outcome Measures
Name Time Method Number of Participants With Hospital Recovery Scale on Day 6 Day 6 The hospital recovery scale assesses a participant's clinical status. The scale provides 6 mutually exclusive conditions ordered from best to worst: 1) not hospitalized; 2) non-ICU hospitalization, not requiring supplemental oxygen; 3) non-ICU hospitalization, requiring supplemental oxygen; 4) admitted to the ICU, not requiring invasive mechanical ventilation; 5) requiring invasive mechanical ventilation; and 6) death.
- Secondary Outcome Measures
Name Time Method Viral Load Over Time Baseline, Days 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 14 and 19 Viral load over time was measured by quantitative real time polymerase chain reaction (qRT-PCR) and viral culture in the mid-turbinate (MT) nasal swabs and endotracheal samples.
Number of Participants With Adverse Events as a Measure of Safety and Tolerability Up to Day 33 An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
Number of Participants With Clinically Significant Changes in Laboratory Tests Up to Day 33 Number of participants with clinically significant changes in laboratory tests were reported. Blood samples for hematology, serum chemistry, and urinalysis were collected at predefined time points for clinical laboratory testing.
Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Up to Day 33 Number of participants with clinically significant changes in Electrocardiogram (ECG) was reported.
Time to Hospital Discharge Up to Day 33 The time to hospital discharge was defined as the time from start of study drug to hospital discharge.
Number of Participants With Adjudicated Influenza Complications Up to Day 33 Influenza complications include pulmonary complications (such as respiratory failure, primary viral pneumonia, secondary bacterial pneumonia \[including pneumonia attributable to unusual pathogens\], exacerbations of chronic underlying pulmonary diseases such as chronic obstructive pulmonary disease \[COPD\] and asthma) and extrapulmonary complications (such as cardiovascular and cerebrovascular diseases \[for example, myocardial infarction, congestive heart failure, arrhythmia, stroke\], muscular disorders \[for example, myositis, rhabdomyolysis\], central nervous system \[CNS\] involvement, acute exacerbation of chronic kidney disease, decompensation of previously controlled diabetes mellitus, other infections \[for example, sinusitis and otitis\]).
Number of Participants With Emergence of Viral Resistance to Pimodivir Up to Day 33 Emergence of viral resistance to Pimodivir was detected by genotyping and/or phenotyping. Nasal MT swabs and endotracheal samples were used for sequence analysis of the polymerase basic protein (PB)2 region of the influenza polymerase gene, and of neuraminidase (NA) genes for participants using an NA inhibitor (NAI) as part of their Standard of Care (SOC).
Plasma Concentration of Pimodivir Day 1: 1 hour30minutes to 6 hours postdose, Day 3: Predose, Day 5: Predose and 1 hour30minutes to 6 hours postdose, Day 6: 12 hours postdose Plasma concentration of Pimodivir was reported.
Number of Participants With Clinically Significant Changes in Vital Signs Up to Day 33 Number of participants with clinically significant changes in vital signs (temperature, pulse rate, respiratory rate and blood pressure) was reported.
Trial Locations
- Locations (266)
University Of Maryland Medical Center
🇺🇸Baltimore, Maryland, United States
Nea Baptist Clinic
🇺🇸Jonesboro, Arkansas, United States
Western Michigan University Homer Stryker M.D. School of Medicine Center for Clinical Research
🇺🇸Kalamazoo, Michigan, United States
University of Texas Southwestern Medical Center
🇺🇸Dallas, Texas, United States
DM Clinical Research
🇺🇸Tomball, Texas, United States
UCSF Fresno
🇺🇸Fresno, California, United States
Sanatorio Juan XXIII
🇦🇷General Roca, Argentina
Anne Arundel Medical Center
🇺🇸Annapolis, Maryland, United States
Destin Pulmonary Critical Care, PLLS.
🇺🇸Santa Rosa Beach, Florida, United States
Northside Hospital
🇺🇸Atlanta, Georgia, United States
William Beaumont Hospital
🇺🇸Troy, Michigan, United States
Infection Control Ltda
🇧🇷Brasil, Brazil
Hosp. Mutua Terrassa
🇪🇸Terrassa, Spain
Centre Hospitalier d'Agen
🇫🇷Agen cedex 9, France
Nemocnice Na Bulovce
🇨🇿Praha 8, Czechia
Pauls Stradins Clinical University Hospital
🇱🇻Riga, Latvia
Hôpital Bichat - Claude Bernard
🇫🇷Paris, France
ASST Grande Ospedale Metropolitano Niguarda
🇮🇹Milano, Italy
Azienda Ospedaliera Universitaria Maggiore della CaritÃ
🇮🇹Novara, Italy
Siauliai Republican Hospital, Public Institution
🇱🇹Siauliai, Lithuania
Azienda Ospedaliera Universitaria Integrata Verona
🇮🇹Verona, Italy
Hallym University Dongtan Sacred Heart Hospital
🇰🇷Hwaseong-si, Korea, Republic of
Chungbuk National University Hospital
🇰🇷Cheongju-si, Korea, Republic of
Yonsei University Wonju Severance Christian Hospital
🇰🇷Gangwon-do, Korea, Republic of
Konkuk University Medical Center
🇰🇷Seoul, Korea, Republic of
Ziv Medical Center
🇮🇱Safed, Israel
Dong-A University Hospital
🇰🇷Pusan, Korea, Republic of
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
🇮🇹Milano, Italy
Ospedale San Giuseppe - Fatebenefratelli
🇮🇹Milano, Italy
Soroka University Medical Center
🇮🇱Beersheba, Israel
Korea University Anam Hospital
🇰🇷Seoul, Korea, Republic of
Galilee Medical Center
🇮🇱Nahariya, Israel
Tudogyogyintezet Torokbalint
ðŸ‡ðŸ‡ºTorokbalint, Hungary
Chaim Sheba Medical Center
🇮🇱Ramat Gan, Israel
Waikato Hospital
🇳🇿Hamilton, New Zealand
Hallym University Kangnam Sacred Heart Hospital
🇰🇷Seoul, Korea, Republic of
Children's Clinical University Hospital
🇱🇻Riga, Latvia
Jeroen Bosch Ziekenhuis
🇳🇱s-Hertogenbosch, Netherlands
Wellington Hospital
🇳🇿Wellington, New Zealand
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Albert Schweitzer Ziekenhuis
🇳🇱Dordrecht, Netherlands
Clinical Infectious Diseases Hospital n. a. S.P. Botkin
🇷🇺St. Petersburg, Russian Federation
Hosp. Univ. 12 de Octubre
🇪🇸Madrid, Spain
Christchurch Hospital
🇳🇿Christchurch, New Zealand
Hosp. Univ. Virgen de Las Nieves
🇪🇸Granada, Spain
Hosp. De Mataro
🇪🇸Mataro, Spain
Tauranga Hospital
🇳🇿Tauranga, New Zealand
The Catholic University of Korea St. Vincent's Hospital
🇰🇷Suwon-si, Korea, Republic of
Emmed Research
🇿🇦Pretoria, South Africa
Hosp. Univ. San Cecilio
🇪🇸Granada, Spain
Hosp. Univ. Ramon Y Cajal
🇪🇸Madrid, Spain
Clinical Research Centre University of Cape Town
🇿🇦Cape Town, South Africa
Hosp. Alvaro Cunqueiro
🇪🇸Vigo, Spain
Aberdeen Royal Infirmary
🇬🇧Aberdeen, United Kingdom
Norrlands Universitetssjukhus
🇸🇪Umeå, Sweden
JM Research, SC
🇲🇽Cuernavaca, Mexico
Johese Unitas
🇿🇦Centurion, South Africa
Abdullah, IA
🇿🇦Durban, South Africa
Hosp. Univ. La Paz
🇪🇸Madrid, Spain
City Hospital #8
🇷🇺Chelyabinsk, Russian Federation
Sebastian, Peter
🇿🇦Durban, South Africa
Akademiska Sjukhuset
🇸🇪Uppsala, Sweden
Hospital Civil de Guadalajara Dr. Juan I. Menchaca
🇲🇽Guadalajara, Mexico
Nemocnica s poliklinikou S. Kukuru Michalovce, a.s.
🇸🇰Michalovce, Slovakia
Hosp. Univ. de La Princesa
🇪🇸Madrid, Spain
LLC Reafarm
🇷🇺Stavropol, Russian Federation
Leeds General Infirmary
🇬🇧Leeds, United Kingdom
Hosp. Clinico San Carlos
🇪🇸Madrid, Spain
Kharkiv MA of PGE Ch of inf.dis. BO Kharkiv Reg.Cl.inf.Hosp.
🇺🇦Kharkiv, Ukraine
Centrum Medyczne w Lancucie Sp.z o.o.
🇵🇱Lancut, Poland
DJW Research
🇿🇦Krugersdorp, South Africa
Nemocnica arm. generala L. Svobodu Svidnik, a.s.,
🇸🇰Svidnik, Slovakia
North Manchester General Hospital
🇬🇧Manchester, United Kingdom
Kyiv Oleksandrivska Clinical Hospital
🇺🇦Kyiv, Ukraine
Karadeniz Teknik University Medical Faculty
🇹🇷Trabzon, Turkey
National University Hospital
🇸🇬Singapore, Singapore
NZOZ Centrum Badań Klinicznych,Piotr Napora,Lekarze Spółka Partnerska
🇵🇱Wroclaw, Poland
Hosp. Univ. de Getafe
🇪🇸Getafe, Spain
Hosp. Univ. Donostia
🇪🇸Donostia-San Sebastian, Spain
Hosp. Gral. Univ. de Elche
🇪🇸Elche, Spain
Clinical Hospital #3
🇷🇺Yaroslavl, Russian Federation
Into Research
🇿🇦Pretoria, South Africa
Limpopo Clinical Research Initiative
🇿🇦Thabazimbi, South Africa
CCH #1 Vinnytsia M.I. Pyrogov NMU Ch of Propaedeutics of IM
🇺🇦Vinnytsia, Ukraine
Hacettepe University Medical Faculty
🇹🇷Samanpazari, Altindag, Turkey
Western General Hospital
🇬🇧Edinburgh, United Kingdom
Adnan Menderes University
🇹🇷Aydin, Turkey
Tri-Service General Hospital
🇨🇳Taipei, Taiwan
Dicle University Medical Faculty
🇹🇷Diyarbakir, Turkey
Musgrove Park Hospital
🇬🇧Taunton, United Kingdom
UMC Utrecht
🇳🇱Utrecht, Netherlands
Gelre Ziekenhuizen Zutphen
🇳🇱Zutphen, Netherlands
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
UC Health LLC
🇺🇸Cincinnati, Ohio, United States
Wayne State Univ School of Medicine
🇺🇸Detroit, Michigan, United States
Henry Ford Hospital
🇺🇸Detroit, Michigan, United States
Wayne State University
🇺🇸Detroit, Michigan, United States
Ospedale San Raffaele- Sede Distaccata Ospedale S. Raffaele Turro
🇮🇹Milano, Italy
AOU Policlinico di Modena
🇮🇹Modena, Italy
BAPS Pramukhswami Hospital
🇮🇳Surat, India
Mercury Street Medical Group, PLLC
🇺🇸Butte, Montana, United States
Augusta University
🇺🇸Augusta, Georgia, United States
Saint Michael's Medical Center
🇺🇸Newark, New Jersey, United States
Social Medizinisches Zentrum Baumgartner Höhe - Otto Wagner Spital
🇦🇹Wien, Austria
Regents of the University of Minnesota
🇺🇸Minneapolis, Minnesota, United States
Apollo Hospitals International Limited
🇮🇳Gandhinagar, India
S. R. Kalla Memorial General Hospital
🇮🇳Jaipur, India
Eternal Heart Care Centre
🇮🇳Jaipur, India
Centre of Tuberculosis and Lung Diseases
🇱🇻Riga District, Latvia
Hospital Sultanah Bahiyah
🇲🇾Alor Setar, Malaysia
Vinaya Hospital and Research Center
🇮🇳Mangalore, India
M S Ramaiah Memorial Hospital
🇮🇳Bangalore, India
Ajanta Research Cemtre
🇮🇳Lucknow, India
Hospital of Rezekne
🇱🇻Rezekne, Latvia
Klaipeda University Hospital
🇱🇹Klaipeda, Lithuania
Hospital Sultanah Nur Zahirah
🇲🇾Kuala, Malaysia
Hospital Miri
🇲🇾Miri, Malaysia
Hospital Sibu
🇲🇾Sibu, Malaysia
Hospital Infantil de Mexico Federico Gomez
🇲🇽Ciudad De Mexico, Mexico
Tan Tock Seng Hospital
🇸🇬Singapore, Singapore
Changi General Hospital
🇸🇬Singapore, Singapore
Sahyadri Speciality Hospital
🇮🇳Pune, India
Vidzemes Hospital
🇱🇻Valmiera, Latvia
Hospital Umum Sarawak
🇲🇾Kuching, Malaysia
Hospital Sungai Buloh
🇲🇾Sungai Buloh, Malaysia
Hospital Taiping
🇲🇾Taiping, Malaysia
Hospital Civil de Guadalajara Fray Antonio Alcalde
🇲🇽Guadalajara, Mexico
Clinica Peruano Americana S.A
🇵🇪Trujillo, Peru
Nemocnica Malacky, Nemocnicna A.S.
🇸🇰Malacky, Slovakia
Bumrungrad Hospital
🇹ðŸ‡Wattana, Thailand
Regional Hospital of Liepaja
🇱🇻Liepaja, Latvia
Hospital Tuanku Jaafar
🇲🇾Seremban, Malaysia
Bach Mai Hospital
🇻🇳Hanoi, Vietnam
National Hospital for Tropical Diseases
🇻🇳Hanoi, Vietnam
Children's Hospital 2
🇻🇳Ho Chi Minh, Vietnam
Taipei Medical University-Wan Fang Hospital
🇨🇳Taipei, Taiwan
Kasturba Medical College Hospital
🇮🇳Manipal, India
Siddhi Hospital
🇮🇳Nashik, India
Riga East Clinical University Hospital
🇱🇻Riga, Latvia
Infectious Diseases Center of Vilnius University Hospital Santaros klinikos
🇱🇹Vilnius, Lithuania
Hospital Queen Elizabeth
🇲🇾Kota Kinabalu, Malaysia
Hospital Universitario 'Dr. Jose Eleuterio Gonzalez'
🇲🇽Mexico, Mexico
DFNsP Bratislava
🇸🇰Bratislava, Slovakia
Srinagarind Hospital
🇹ðŸ‡Muang, Thailand
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
Siriraj Hospital
🇹ðŸ‡Bangkok, Thailand
Bamrasnaradura Infectious Disease Institute
🇹ðŸ‡Muang, Thailand
Nguyen Tri Phuong Hospital
🇻🇳Ho Chi Minh, Vietnam
Children's Hospital 1
🇻🇳Ho Chi Minh, Vietnam
Thanh Nhan Hospital
🇻🇳Hanoi, Vietnam
Department for Heart Failure and Valvular Disease
🇸🇪Malmö, Sweden
Kocaeli University Medical Faculty
🇹🇷Kocaeli, Turkey
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Sapir Medical Center, Meir Hospital
🇮🇱Kfar-Saba, Israel
Rabin Medical Center, Beilinson Campus
🇮🇱Petach Tikva, Israel
Kaplan Medical Center
🇮🇱Rechovot, Israel
Tel Aviv Sourasky Medical Center
🇮🇱Tel Aviv, Israel
Centre Hospitalier Départemental
🇫🇷La Roche S/ Yon Cedex 9, France
Korea University Guro Hospital
🇰🇷Seoul, Korea, Republic of
Gachon University Gil Medical Center
🇰🇷Incheon, Korea, Republic of
Hosp. Univ. Hm Monteprincipe
🇪🇸Madrid, Spain
Hosp. Clinico Univ. de Santiago
🇪🇸Santiago de Compostela, Spain
Irmandade Da Santa Casa de Misericordia de Sao Paulo
🇧🇷São Paulo, Brazil
Miller Children's at Long Beach Medical Center
🇺🇸Long Beach, California, United States
Stanford University School of Medicine
🇺🇸Stanford, California, United States
Washington University
🇺🇸Saint Louis, Missouri, United States
Holy Name Medical Center
🇺🇸Teaneck, New Jersey, United States
Montefiore Medical Center PRIME
🇺🇸Bronx, New York, United States
Lowcountry Infectious Diseases
🇺🇸Charleston, South Carolina, United States
CEMIC (Centro de Educación Médica e Investigaciones ClÃnicas)
🇦🇷C.a.b.a., Argentina
Hospital Interzonal General de Agudos Dr. Jose Penna
🇦🇷Bahia Blanca, Argentina
Hospital Nuestra Señora de la Misericordia
🇦🇷Cordoba, Argentina
Hospital Cordoba
🇦🇷Cordoba, Argentina
Hospital Rawson
🇦🇷Córdoba, Argentina
Hospital Privado Centro Medico de Cordoba
🇦🇷Cordoba, Argentina
Hospital San Roque
🇦🇷Córdoba, Argentina
Instituto Medico Platense
🇦🇷La Plata, Argentina
Hospital Italiano de La Plata
🇦🇷La Plata Lpl Lpl, Argentina
Flinders Medical Centre
🇦🇺Bedford Park, Australia
Box Hill Hospital
🇦🇺Box Hill, Australia
Hospital Universitario Austral
🇦🇷Pilar, Argentina
Sanatorio Britanico S.A.
🇦🇷Rosario, Argentina
Mater Hospital Brisbane
🇦🇺South Brisbane, Australia
The Alfred Hospital
🇦🇺Melbourne, Australia
Royal Melbourne Hospital
🇦🇺Melbourne, Australia
Townsville Hospital
🇦🇺Townsville, Australia
AKH - Medizinische Universität Wien
🇦🇹Wien, Austria
SMZ Süd - Kaiser Franz Josef Spital Wien
🇦🇹Wien, Austria
Institut Jules Bordet
🇧🇪Brussel, Belgium
CHU Saint-Pierre
🇧🇪Bruxelles, Belgium
ULB Hôpital Erasme
🇧🇪Bruxelles, Belgium
Santa Casa de Misericordia de Belo Horizonte
🇧🇷Belo Horizonte, Brazil
Irmandade Santa Casa de Misericordia de Porto Alegre - Hospital da Crianca Santo Antonio
🇧🇷Porto Alegre, Brazil
Cardresearch - Cardiologia Assistencial
🇧🇷Belo Horizonte, Brazil
Hospital de ClÃnicas de Porto Alegre
🇧🇷Porto Alegre, Brazil
Hospital Sao Vicente de Paulo
🇧🇷Passo Fundo, Brazil
Hospital São Lucas da PUCRS
🇧🇷Porto Alegre, Brazil
Hospital da Luz
🇧🇷Sao Paulo, Brazil
Hospital de Medicina de São José do Rio Preto
🇧🇷São José do Rio Preto, Brazil
SHATPPD - Sofia District EOOD
🇧🇬Sofia, Bulgaria
Fifth Multiprofile Hospital for Active Treatment - MHAT - Sofia EAD
🇧🇬Sofia, Bulgaria
Multiprofile Hospital for Active Treatment - MHAT Lyulin EAD
🇧🇬Sofia, Bulgaria
SHATPPD - Ruse Ltd.
🇧🇬Ruse, Bulgaria
Fundacao Jose Luiz Egydio Setubal
🇧🇷São Paulo, Brazil
Military Medical Academy - Sofia
🇧🇬Sofia, Bulgaria
MHAT Dr Stefan Cherkezov
🇧🇬Veliko Tarnovo, Bulgaria
Hospital Dr Sotero del Rio
🇨🇱Puente Alto, Chile
Health Sciences North Horizon Sante-Nord
🇨🇦Sudbury, Ontario, Canada
University of British Columbia
🇨🇦Vancouver, Canada
Hospital El Pino
🇨🇱San Bernardo, Chile
The Third Xiangya Hospital, Central South University
🇨🇳Changsha, China
Nanfang Hospital
🇨🇳Guangzhou, China
Wuxi People's Hospital
🇨🇳Wuxi, China
Henan province people's hospital
🇨🇳Zhengzhou, China
Nemocnice Kyjov, p.o.
🇨🇿Kyjov, Czechia
Fakultni nemocnice Brno
🇨🇿Brno, Czechia
CHU Amiens - Hopital Sud
🇫🇷Amiens Cedex, France
Hopital Louis Mourier
🇫🇷Colombes, France
Centre Hospitalier Intercommunal de Créteil
🇫🇷Creteil cedex, France
CHU Dijon
🇫🇷Dijon, France
CHU de Grenoble - Hôpital Albert Michallon
🇫🇷La Tronche, France
Hopital Edouard Herriot - CHU Lyon
🇫🇷Lyon, France
CHU de Limoges, Hopital Dupuytren
🇫🇷Limoges, France
CHU de Nice, Hopital de l'Archet
🇫🇷Nice Cedex 3, France
Hopital Saint-Louis
🇫🇷Paris cedex 10, France
CHU Nantes - Hotel Dieu
🇫🇷Nantes Cedex 1, France
Hôpital Nord - Marseille
🇫🇷Marseille cedex 20, France
Hopital Cochin
🇫🇷Paris, France
CHU Poitiers - Hôpital la Milétrie
🇫🇷Poitiers, France
CHU Saint-Etienne - Hôpital Nord
🇫🇷Saint-Etienne Cedex 2, France
Klinikum Donaustauf
🇩🇪Donaustauf, Germany
Universitaetsklinikum Koeln
🇩🇪Koeln, Germany
Universitaetsklinikum Giessen und Marburg GmbH
🇩🇪Hessen, Germany
Klinikum Weiden
🇩🇪Weiden, Germany
Universitaetsklinikum Schleswig-Holstein - Campus Luebeck
🇩🇪Luebeck, Germany
Universitaetsklinik Erlangen
🇩🇪Erlangen, Germany
Veszprem Megyei Tudogyogyintezete
ðŸ‡ðŸ‡ºFarkasgyepü, Hungary
Zydus Hospital-Ahmedabad
🇮🇳Ahmedabad, India
Rajiv Gandhi Institute of Medical Sciences
🇮🇳Balaga, India
Aware Global Hospital
🇮🇳Hyderabad, India
Midland Healthcare & Research Center
🇮🇳Lucknow, India
Suretech Hospital and Research Centre Limited
🇮🇳Nagpur, India
BLK Super Specialty Hospital
🇮🇳New Delhi, India
Sir Ganga Ram Hospital
🇮🇳New Delhi, India
Lifepoint Multispecialty Hospital
🇮🇳Pune, India
Fortis Flight Lieutenant Rajan Dhall Hospital
🇮🇳New Delhi, India
Shree Giriraj Multispeciality Hospital
🇮🇳Rajkot, India
Haemek Medical Center
🇮🇱Afula, Israel
Bnai Zion Medical Center
🇮🇱Haifa, Israel
Barzilai Medical Center
🇮🇱Ashkelon, Israel
Rambam Health Care Campus
🇮🇱Haifa, Israel
Wolfson Medical Center
🇮🇱Holon, Israel
Hadassah University Hospita - Ein Kerem
🇮🇱Jerusalem, Israel
Fondazione IRCCS Ospedale Maggiore Policlinico,Mangiagalli e Regina Elena
🇮🇹Milano, Italy
Azienda Socio Sanitaria Territoriale di Monza Presidio San Gerardo
🇮🇹Monza, Italy
Azienda Ospedaliero Universitaria Policlinico Paolo Giaccone
🇮🇹Palermo, Italy
Lazzaro Spallanzani IRCCS
🇮🇹Roma, Italy
The Catholic University of Korea, Incheon St. Mary's Hospital
🇰🇷Incheon, Korea, Republic of
Korea University Ansan Hospital
🇰🇷Ansan-si, Korea, Republic of
Hosp. Clinic I Provincial de Barcelona
🇪🇸Barcelona, Spain
Hosp. Univ. de Bellvitge
🇪🇸L'Hospitalet de Llobregat, Spain
Kaohsiung Medical University Chung-Ho Memorial Hospital
🇨🇳Kaohsiung, Taiwan
Communal Institution Central City Hospital
🇺🇦Zhytomyr, Ukraine
Poltava Regional Clinical Hospital HSEI of Ukraine Ukrainian Medical Stomatological Academy
🇺🇦Poltava, Ukraine
Szpital Miejski ZOZ
🇵🇱Debica, Poland
Rhode Island Hospital
🇺🇸Providence, Rhode Island, United States