Outcome Study Assessing a 75 Milligrams (mg) Dose of Macitentan in Patients With Pulmonary Arterial Hypertension
- Conditions
- Pulmonary Arterial Hypertension
- Interventions
- Registration Number
- NCT04273945
- Lead Sponsor
- Actelion
- Brief Summary
The purpose of this study is to demonstrate superiority of macitentan 75 milligrams (mg) in prolonging the time to the first clinical events committee (CEC)-adjudicated morbidity or mortality (M/M) event in participants with symptomatic pulmonary arterial hypertension (PAH) compared to macitentan 10 mg.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 935
- Target population: greater than or equal to (>=) 18 (or the legal age of consent in the jurisdiction in which the study is taking place) years of age
- Target population: Symptomatic Pulmonary Arterial Hypertension (PAH) in World Health Organization Functional Class (WHO FC) II, III, or IV
- Target population: PAH subtype falling in one of the below classifications: Idiopathic; Heritable; Drug- or toxin-induced; Related to: Connective tissue disease, HIV infection, Portal hypertension, and Congenital heart disease with small/coincidental cardiac defect with systemic-to-pulmonary shunt (for example atrial septal defect, ventricular septal defect, patent ductus arteriosus, atrioventricular septal defect) which does not account for the elevated pulmonary vascular resistance (PVR) or persistent PAH documented by an Right heart catheterization (RHC) >= 1 year after simple systemic-to pulmonary shunt repair
- PAH diagnosis confirmed by hemodynamic evaluation at rest at any time prior to screening: Mean pulmonary artery pressure (mPAP) greater than (>) 20 millimeters of mercury (mm Hg), and; Pulmonary artery wedge pressure (PAWP) or left ventricular end diastolic pressure (LVEDP) less than or equal to (<=) 15 mm Hg, and PVR >= 3 Wood Units (that is, >= 240 dyn*sec/cm^5)
- Able to perform the 6-minute walking test (6MWT) with a minimum distance of 50 meters (m) and maximum distance of 440m at screening. Participants able to walk more than 440m at screening are eligible if they are in WHO FC III or IV and n-terminal prohormone of brain natriuretic peptide or n-terminal pro B-type natriuretic peptide (NT-proBNP) level is >=300 nanograms per liter (ng/L) at screening, based on central laboratory results
- Known presence of three or more of the following risk factors for heart failure with preserved ejection fraction at screening, based on records that confirm documented medical history: Body mass index (BMI) > 30 kilograms per meter square (kg/m^2), Diabetes mellitus of any type, Essential hypertension (even if well controlled); Coronary artery disease, that is, any of the following: history of stable angina, or known more than 50 percent (%) stenosis in a coronary artery, or history of myocardial infarction, or history of or planned coronary artery bypass grafting and/or coronary artery stenting
- Presence of moderate or severe obstructive lung disease (forced expiratory volume in 1 second [FEV1] / forced vital capacity [FVC] < 70%; and FEV1 < 60% of predicted after bronchodilator administration) ) in participants with a known or suspected history of significant lung disease as documented by a spirometry test performed within 1 year prior to screening
- Known moderate to severe hepatic impairment, defined as Child-Pugh Class B or C, based on records that confirm documented medical history
- Serum aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) > 1.5*upper limit of normal (ULN) at screening
- Hemoglobin < 100 gram per liter (g/L) (< 10 gram per deciliter [g/dL]) at screening
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Macitentan 10 milligrams (mg) + Placebo Macitentan 75 mg Run-in period:Participants who are either endothelin receptor antagonist (ERA)-naïve or who are receiving daily dose of macitentan or ambrisentan less (\<) 10 milligrams (mg), or daily dose of bosentan \<250 mg, will enter 4-week open-label run-in period with macitentan 10 mg prior to randomization. ERA-pre-treated participants will bypass run-in period and will be randomized to either macitentan 75 mg or macitentan 10 mg directly.Double-blind Treatment (DBT) Period:Participants will receive macitentan 10 mg orally up to End of DBT.To maintain blind, participants will receive macitentan 37.5 mg-matching placebo for 4 weeks and macitentan 75 mg-matching placebo thereafter up to DBT.Treatment Extension Period:After EDBT, participants will receive macitentan 37.5 mg once a day (qd) orally for 4 weeks, prior to receiving open-label macitentan 75 mg qd orally for 2 years. To maintain blind, participants will receive macitentan 75 mg-matching placebo during 4-week uptitration. Macitentan 10 milligrams (mg) + Placebo Macitentan 10 mg Run-in period:Participants who are either endothelin receptor antagonist (ERA)-naïve or who are receiving daily dose of macitentan or ambrisentan less (\<) 10 milligrams (mg), or daily dose of bosentan \<250 mg, will enter 4-week open-label run-in period with macitentan 10 mg prior to randomization. ERA-pre-treated participants will bypass run-in period and will be randomized to either macitentan 75 mg or macitentan 10 mg directly.Double-blind Treatment (DBT) Period:Participants will receive macitentan 10 mg orally up to End of DBT.To maintain blind, participants will receive macitentan 37.5 mg-matching placebo for 4 weeks and macitentan 75 mg-matching placebo thereafter up to DBT.Treatment Extension Period:After EDBT, participants will receive macitentan 37.5 mg once a day (qd) orally for 4 weeks, prior to receiving open-label macitentan 75 mg qd orally for 2 years. To maintain blind, participants will receive macitentan 75 mg-matching placebo during 4-week uptitration. Macitentan 10 milligrams (mg) + Placebo Macitentan 37.5 mg Run-in period:Participants who are either endothelin receptor antagonist (ERA)-naïve or who are receiving daily dose of macitentan or ambrisentan less (\<) 10 milligrams (mg), or daily dose of bosentan \<250 mg, will enter 4-week open-label run-in period with macitentan 10 mg prior to randomization. ERA-pre-treated participants will bypass run-in period and will be randomized to either macitentan 75 mg or macitentan 10 mg directly.Double-blind Treatment (DBT) Period:Participants will receive macitentan 10 mg orally up to End of DBT.To maintain blind, participants will receive macitentan 37.5 mg-matching placebo for 4 weeks and macitentan 75 mg-matching placebo thereafter up to DBT.Treatment Extension Period:After EDBT, participants will receive macitentan 37.5 mg once a day (qd) orally for 4 weeks, prior to receiving open-label macitentan 75 mg qd orally for 2 years. To maintain blind, participants will receive macitentan 75 mg-matching placebo during 4-week uptitration. Macitentan 75 mg + Placebo Macitentan 37.5 mg Run-in period:Participants who are either ERA-naive or who are receiving a daily dose of macitentan or ambrisentan \<10 mg, or a daily dose of bosentan \<250 mg, will enter 4-week open-label run-in period with macitentan 10 mg prior to randomization. ERA-pre-treated patients will bypass the run-in period and will be randomized to either macitentan 75 mg or macitentan 10 mg directly.DBT Period: participants will receive macitentan 37.5 mg orally for 4 weeks and macitentan 75 mg thereafter up to End of DBT. To maintain the blind, participants will receive macitentan 10 mg-matching placebo up to End of DBT.Treatment Extension Period: After EDBT, participants will continue to receive macitentan 75 mg orally for 2 years. To maintain the blind, participants will receive macitentan 37.5 mg-matching placebo during the 4-week up-titration period. Macitentan 75 mg + Placebo Macitentan 75 mg Run-in period:Participants who are either ERA-naive or who are receiving a daily dose of macitentan or ambrisentan \<10 mg, or a daily dose of bosentan \<250 mg, will enter 4-week open-label run-in period with macitentan 10 mg prior to randomization. ERA-pre-treated patients will bypass the run-in period and will be randomized to either macitentan 75 mg or macitentan 10 mg directly.DBT Period: participants will receive macitentan 37.5 mg orally for 4 weeks and macitentan 75 mg thereafter up to End of DBT. To maintain the blind, participants will receive macitentan 10 mg-matching placebo up to End of DBT.Treatment Extension Period: After EDBT, participants will continue to receive macitentan 75 mg orally for 2 years. To maintain the blind, participants will receive macitentan 37.5 mg-matching placebo during the 4-week up-titration period. Macitentan 75 mg + Placebo Placebo Run-in period:Participants who are either ERA-naive or who are receiving a daily dose of macitentan or ambrisentan \<10 mg, or a daily dose of bosentan \<250 mg, will enter 4-week open-label run-in period with macitentan 10 mg prior to randomization. ERA-pre-treated patients will bypass the run-in period and will be randomized to either macitentan 75 mg or macitentan 10 mg directly.DBT Period: participants will receive macitentan 37.5 mg orally for 4 weeks and macitentan 75 mg thereafter up to End of DBT. To maintain the blind, participants will receive macitentan 10 mg-matching placebo up to End of DBT.Treatment Extension Period: After EDBT, participants will continue to receive macitentan 75 mg orally for 2 years. To maintain the blind, participants will receive macitentan 37.5 mg-matching placebo during the 4-week up-titration period. Macitentan 10 milligrams (mg) + Placebo Placebo Run-in period:Participants who are either endothelin receptor antagonist (ERA)-naïve or who are receiving daily dose of macitentan or ambrisentan less (\<) 10 milligrams (mg), or daily dose of bosentan \<250 mg, will enter 4-week open-label run-in period with macitentan 10 mg prior to randomization. ERA-pre-treated participants will bypass run-in period and will be randomized to either macitentan 75 mg or macitentan 10 mg directly.Double-blind Treatment (DBT) Period:Participants will receive macitentan 10 mg orally up to End of DBT.To maintain blind, participants will receive macitentan 37.5 mg-matching placebo for 4 weeks and macitentan 75 mg-matching placebo thereafter up to DBT.Treatment Extension Period:After EDBT, participants will receive macitentan 37.5 mg once a day (qd) orally for 4 weeks, prior to receiving open-label macitentan 75 mg qd orally for 2 years. To maintain blind, participants will receive macitentan 75 mg-matching placebo during 4-week uptitration. Macitentan 75 mg + Placebo Macitentan 10 mg Run-in period:Participants who are either ERA-naive or who are receiving a daily dose of macitentan or ambrisentan \<10 mg, or a daily dose of bosentan \<250 mg, will enter 4-week open-label run-in period with macitentan 10 mg prior to randomization. ERA-pre-treated patients will bypass the run-in period and will be randomized to either macitentan 75 mg or macitentan 10 mg directly.DBT Period: participants will receive macitentan 37.5 mg orally for 4 weeks and macitentan 75 mg thereafter up to End of DBT. To maintain the blind, participants will receive macitentan 10 mg-matching placebo up to End of DBT.Treatment Extension Period: After EDBT, participants will continue to receive macitentan 75 mg orally for 2 years. To maintain the blind, participants will receive macitentan 37.5 mg-matching placebo during the 4-week up-titration period.
- Primary Outcome Measures
Name Time Method Double-blind Treatment Period: Time to First Clinical Events Committee (CEC)-adjudicated Morbidity or Mortality (M/M) Events Up to 4 years Time to first CEC-adjudicated M/M event on-treatment (ie.,up to 7 days after last dose of DB study intervention) is defined as time from randomization to first of following events: All-cause death, including death caused by on-treatment adverse event that occur within 4 weeks of study DB treatment discontinuation;non-planned Pulmonary Arterial Hypertension(PAH)-related hospitalization(including for worsening of PAH, atrial septostomy, lung transplantation with or without heart transplantation, or initiation of parenteral prostacyclins);PAH-related disease progression, defined as worsening of World Health Organization(WHO) Functional Class(FC) from baseline or deterioration by at least 15% in exercise capacity, as measured by 6-minute walk distance(6MWD), from baseline and confirmed by second 6MWD test performed on different day within 2 week of initial test or appearance or worsening of signs or symptoms of right-sided heart failure that require initiation of intravenous diuretics.
- Secondary Outcome Measures
Name Time Method Double-blind Treatment Period: Change From Baseline to Week 24 in 6MWD Baseline up to Week 24 The 6MWT is a non-encouraged test performed to quantify exercise tolerance and capacity. This standardized test measures the distance an individual is able to walk over a total of six minutes on a hard, flat surface. The goal is for the individual to walk as far as possible in six minutes.
Double-blind Treatment Period: Number of Participants with CEC-adjudicated Death due to PAH and/or Hospitalizations for PAH (First and Recurrent) Events on-treatment Up to 4 years Number of Participants with CEC-adjudicated death or hospitalization due to PAH will be reported.
Double-blind Treatment Period: Change From Baseline to Week 24 in PAH Symptoms Based on PAH-SYMPACT Questionnaire- Cardiopulmonary Symptom Domain Score Baseline up to Week 24 The Cardiopulmonary Symptoms domain consists of 6 items reported on a 5-point Likert scale (from 0 to 4). The value 0 means "no symptom" and value 4 corresponds to "very severe symptoms". The symptoms part of the PAH symptoms and impact questionnaire (PAH-SYMPACT) is completed daily for a 7-day period. The recall period of symptom items is the last 24 hours. An average Cardiopulmonary Symptoms domain score is determined based on the daily scores of the 6 items.
Double-blind Treatment Period: Change From Baseline to Week 24 in PAH Symptoms Based on PAH-SYMPACT Questionnaire- Cardiovascular Symptom Domain Score Baseline up to Week 24 The Cardiovascular Symptoms domain consists of 5 items reported on a 5-point Likert scale (from 0 to 4). The value 0 corresponds to "no symptoms" and value 4 corresponds to "very severe symptoms". The symptoms part of the PAH-SYMPACT is completed daily for a 7 day period. The recall period of symptom items is the last 24 hours. An average cardiovascular symptoms domain score is determined based on the daily scores of the 5 items.
Double-blind Treatment Period: Time to Death Occurring Between Randomization and End of Double-blind Treatment (EDBT) Up to 4 years Time to death occurring between randomization and EDBT will be reported.
Treatment Extension Period: Time to Death Occurring Between Randomization and End of Study (EOS) Up to 6 years Time to death occurring between randomization and EOS will be reported.
Trial Locations
- Locations (273)
Uniwersytecki Szpital Kliniczny w Bialymstoku
🇵🇱Bialystok, Poland
SPSK nr 7 SUM w Katowicach Gornoslaskie Centrum Medyczne im Prof Leszka Gieca
🇵🇱Katowice, Poland
Krakowski Szpital Specjalityczny im Jana Pawla II Oddzial Kliniczny Chorob Serca i Naczyn
🇵🇱Krakow, Poland
Wojewodzki Szpital Specjalistyczny we Wroclawiu Osrodek Badawczo Rozwojowy
🇵🇱Wroclaw, Poland
Mayo Clinic
🇺🇸Phoenix, Arizona, United States
Arizona Pulmonary Specialists, Ltd
🇺🇸Scottsdale, Arizona, United States
Scripps Memorial Hospital
🇺🇸La Jolla, California, United States
USC Keck
🇺🇸Los Angeles, California, United States
Jeffrey S. Sager, MD Medical Corporation
🇺🇸Santa Barbara, California, United States
Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
🇺🇸Torrance, California, United States
National Jewish Health
🇺🇸Denver, Colorado, United States
Cleveland Clinic
🇺🇸Weston, Florida, United States
Piedmont Healthcare
🇺🇸Atlanta, Georgia, United States
Northside Hospital
🇺🇸Atlanta, Georgia, United States
Advocate Christ Medical Center
🇺🇸Oak Lawn, Illinois, United States
Indiana University
🇺🇸Indianapolis, Indiana, United States
St. Vincent Medical Group, Inc.
🇺🇸Indianapolis, Indiana, United States
University Of Iowa - Hospitals & Clinics
🇺🇸Iowa City, Iowa, United States
Norton Pulmonary Specialists
🇺🇸Louisville, Kentucky, United States
Louisiana State University
🇺🇸New Orleans, Louisiana, United States
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
Troy Beaumont
🇺🇸Troy, Michigan, United States
Washington University School Of Medicine
🇺🇸Saint Louis, Missouri, United States
Saint Louis University Academic Pavillion
🇺🇸Saint Louis, Missouri, United States
University of Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States
Reno Heart Institute
🇺🇸Reno, Nevada, United States
Winthrop University Hospital
🇺🇸Mineola, New York, United States
Mount Sinai
🇺🇸New York, New York, United States
Columbia University
🇺🇸New York, New York, United States
Stony Brook University Medical Center
🇺🇸Stony Brook, New York, United States
Duke
🇺🇸Durham, North Carolina, United States
Lindner Clinical Trial Center/Christ Hospital
🇺🇸Cincinnati, Ohio, United States
Integris Baptist Office
🇺🇸Oklahoma City, Oklahoma, United States
The Oregon Clinic
🇺🇸Portland, Oregon, United States
Oregon Pulmonary Clinic
🇺🇸Portland, Oregon, United States
Oregon Health And Science University
🇺🇸Portland, Oregon, United States
University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
Allegheny General Hospital of Research
🇺🇸Pittsburgh, Pennsylvania, United States
Lankenau Medical Center
🇺🇸Wynnewood, Pennsylvania, United States
AnMed Health
🇺🇸Anderson, South Carolina, United States
UT Southwestern Medical Center
🇺🇸Dallas, Texas, United States
Baylor College of Medicine (BCM) - Baylor Heart Clinic
🇺🇸Houston, Texas, United States
Baylor Scott White - Plano
🇺🇸Plano, Texas, United States
San Antonio Methodist TX Transplant Physicians Group
🇺🇸San Antonio, Texas, United States
The Robert Larner, M.D. College of Medicine at The University of Vermont
🇺🇸Burlington, Vermont, United States
University of Wisconsin Hospital and Clinics
🇺🇸Madison, Wisconsin, United States
Medical College Of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Sanatorio de la Trinidad Mitre
🇦🇷Buenos Aires, Argentina
Sanatorio Guemes
🇦🇷C.a.b.a., Argentina
Hospital Italiano de Buenos Aires
🇦🇷Caba, Argentina
Sanatorio Ramon Cereijo
🇦🇷Caba, Argentina
Centro Médico Dra. De Salvo
🇦🇷Caba, Argentina
Instituto de Cardiologia de Corrientes
🇦🇷Corrientes, Argentina
Instituto Medico de La Fundacion Estudios Clinicos
🇦🇷Rosario, Argentina
Instituto Cardiovascular de Rosario
🇦🇷Rosario, Argentina
Flinders Medical Centre
🇦🇺Bedford Park, Australia
Royal Prince Alfred Hospital
🇦🇺Camperdown, Australia
The Prince Charles Hospital
🇦🇺Chermside, Australia
St Vincent's hospital
🇦🇺Darlinghurst, Australia
Royal Hobart Hospital
🇦🇺Hobart, Australia
Fiona Stanley Hospital
🇦🇺Murdoch, Australia
Westmead Hospital
🇦🇺Westmead, Australia
LKH-Univ. Klinikum Graz
🇦🇹Graz, Austria
Ordensklinikum Linz GmbH Elisabethinen
🇦🇹Linz, Austria
Medical University Vienna
🇦🇹Vienna, Austria
The Republican Scientific-Practical Center ''Cardiology''
🇧🇾Minsk, Belarus
Minsk Regional Clinical Hospital
🇧🇾Minsk, Belarus
ULB Hôpital Erasme
🇧🇪Brussels, Belgium
UZ Leuven
🇧🇪Leuven, Belgium
Universidade Federal De Minas Gerais - Hospital das Clínicas
🇧🇷Belo Horizonte, Brazil
Instituto das Pequenas Missionárias de Maria Imaculada - Hospital Madre Teresa
🇧🇷Belo Horizonte, Brazil
Empresa Brasileira de Servicos Hospitalares-EBSERH-Hospital Universitario de Brasilia
🇧🇷Brasilia, Brazil
Sociedade Hospitalar Angelina Caron - Hospital Angelina Caron
🇧🇷Campina Grande do Sul, Brazil
Ceti - Centro de Estudos Em Terapias Inovadoras
🇧🇷Curitiba, Brazil
Ynova Pesquisa Clinica
🇧🇷Florianopolis, Brazil
Universidade Federal de Goias - Hospital das Clinicas da UFG
🇧🇷Goiania, Brazil
Hospital das Clinicas de Porto Alegre
🇧🇷Porto Alegre, Brazil
Uniao Brasileira de Educacao e Assistencia Hospital Sao Lucas da PUCRS
🇧🇷Porto Alegre, Brazil
Instituto de Medicina Integral Professor Fernando Figueira
🇧🇷Recife, Brazil
Fundacao do ABC Centro Universitario FMABC
🇧🇷Santo Andre, Brazil
Secretaria de Estado da Saude Instituto Dante Pazzanese de Cardiologia
🇧🇷Sao Paulo, Brazil
Hospital Das Clinicas Da Faculdade De Medicina Da USP
🇧🇷Sao Paulo, Brazil
Multiprofile Hospital For Active Treatment National Cardiology Hospital, Ead
🇧🇬Sofia, Bulgaria
University Multiprofile Hospital for Active Treatment- UMHAT Sveta Anna AD
🇧🇬Sofia, Bulgaria
St. Joseph's Health Centre
🇨🇦Hamilton, Ontario, Canada
University of Ottawa Heart Institute
🇨🇦Ottawa, Ontario, Canada
University Health Network - Toronto General Hospital
🇨🇦Toronto, Ontario, Canada
Jewish General Hospital
🇨🇦Montreal, Quebec, Canada
Beijing Chaoyang Hospital
🇨🇳Beijing, China
Beijing Anzhen Hospital
🇨🇳Beijing, China
Peking Union Medical College Hospital
🇨🇳Beijing, China
The Second Xiangya Hospital of Central South Hospital
🇨🇳Changsha, China
West China Hospital Sichuan University
🇨🇳Chengdu, China
The First Affiliated Hospital of Chongqing Medical University
🇨🇳Chongqing, China
The First Affiliated Hospital of Guangzhou Medical University
🇨🇳Guangzhou, China
Shanghai Pulmonary Hospital
🇨🇳Shanghai, China
Renji Hospital
🇨🇳Shanghai, China
Zhongshan Hospital Fudan University
🇨🇳Shanghai, China
The General Hospital of Northern Theater Command
🇨🇳Shenyang, China
Shengjing Hospital Of China Medical University
🇨🇳Shenyang, China
Tianjin Medical University General Hospital
🇨🇳Tianjin, China
The First Affiliated Hospital of Xian Jiaotong University
🇨🇳Xi'An, China
Fundacion Neumologica Colombiana
🇨🇴Bogota, Colombia
Fundacion Cardiovascular de Colombia
🇨🇴Bucaramanga - Piedecuesta - Valle De Menzuli, Colombia
Clínica Imbanaco S.A.S.
🇨🇴Cali, Colombia
Centro Cardiovascular Colombiano Clínica Santa María
🇨🇴Medellin, Colombia
Hospital Universidad del Norte
🇨🇴Soledad, Colombia
General University Hospital II.department of Internal Medicine-cardiology and angiology
🇨🇿Praha 2, Czechia
Århus Universitetshospital, Skejby, Hjertemedicinsk Afdeling B
🇩🇰Arhus, Denmark
CHU de Brest - Hopital de la Cavale Blanche
🇫🇷Brest, France
Hôpital Côte de Nacre
🇫🇷Caen Cedex, France
Hopital Bicetre Aphp Hopitaux Universitaires Paris Sud
🇫🇷Le Kremlin Bicêtre cedex, France
CHRU de Lille Hopital Claude Huriez
🇫🇷Lille Cedex, France
Aphm - Hopital Nord
🇫🇷Marseille Cedex 20, France
Centre Hospitalier Universitaire - de Nice - Hopital Pasteur
🇫🇷Nice, France
CHU Saint Etienne Hopital Nord
🇫🇷St Priest en Jarez Cedex, France
Hopital Larrey CHU de Toulouse
🇫🇷Toulouse Cedex 9, France
Ruhr Universitat Bochum Diabeteszentrum
🇩🇪Bad Oeynhausen, Germany
Medizinische Hochschule Hannover
🇩🇪Hannover, Germany
Medizinische Klinik und Poliklinik V Klinikum Grosshadern der LMU
🇩🇪München, Germany
Universitaetsklinikum Regensburg
🇩🇪Regensburg, Germany
University Hospital of Alexandroupolis
🇬🇷Alexandroupoli, Greece
Alexandra General Hospital of Athens
🇬🇷Athens, Greece
University Hospital Of Larissa
🇬🇷Larisa, Greece
Ahepa University General Hospital of Thessaloniki
🇬🇷Thessaloniki, Greece
Semmelweis Egyetem,Pulmonológiai Klinika
🇭🇺Budapest, Hungary
Gottsegen Gyorgy Orszagos Kardiovaszkularis Intezet Felnott kardiologiai osztaly
🇭🇺Budapest, Hungary
Pecsi Tudomanyegyetem Altalanos Orvostudomanyi Kar
🇭🇺Pecs, Hungary
Szegedi Tudományegyetem, Általános Orvostudományi Kar, Családorvosi Intézet és rendelő
🇭🇺Szeged, Hungary
NHL Medical College (SVP Hospital IMSR)
🇮🇳Ahmedabad, India
Cims Hospital
🇮🇳Ahmedabad, India
Narayana Hrudayalaya Limited
🇮🇳Bangalore, India
SRM Medical College Hospital & Research Centre
🇮🇳Chengalpetu, India
Govindaswamy Kuppuswamy Naidu Memorial Hospital
🇮🇳Coimbatore, India
HealthWorld Hospitals
🇮🇳Durgapur, India
Care Hospitals
🇮🇳Hyderbad, India
Rabindranath Tagore International Institute of Cardiac Sciences
🇮🇳Kolkata, India
GB Pant Institute of Post Graduate Medical Education & Research
🇮🇳New Delhi, India
Sir Ganga Ram Hospital
🇮🇳New Delhi, India
Jawaharlal Institute of Postgraduate Medical Education and Research
🇮🇳Pondicherry, India
B.D. Mehta Mahavir Heart Institute
🇮🇳Surat, India
Carmel Medical Center
🇮🇱Haifa, Israel
Shaare Zedek Medical Center
🇮🇱Jerusalem, Israel
Kaplan Medical Center
🇮🇱Rehovot, Israel
The Chaim Sheba Medical Center
🇮🇱Tel-Hashomer, Israel
Yitzhak Shamir Medical Center
🇮🇱Zerifin, Israel
ASST Grande Ospedale Metropolitano Niguarda
🇮🇹Milano, Italy
AOU Di Modena Policlinico Di Modena
🇮🇹Modena, Italy
Ospedale San Francesco
🇮🇹Nuoro, Italy
Fondazione IRCCS Policlinico San Matteo
🇮🇹Pavia, Italy
Fondazione Toscana Gabriele Monasterio CNR
🇮🇹Pisa, Italy
Policlinico Gemelli Universita Cattolica
🇮🇹Roma, Italy
The University of Tokyo Hospital
🇯🇵Bunkyo, Japan
Kyushu University Hospital
🇯🇵Fukuoka, Japan
Kure Kyosai Hospital
🇯🇵Hiroshima, Japan
Kagoshima University Hospital
🇯🇵Kagoshima City, Japan
St Marianna University Hospital
🇯🇵Kanagawa, Japan
Kanazawa University Hospital
🇯🇵Kanazawa, Japan
Kobe University Hospital
🇯🇵Kobe, Japan
Kurume University Hospital
🇯🇵Kurume, Japan
University Hospital Kyoto Prefectural University of Medicine
🇯🇵Kyoto, Japan
Kyoto University Hospital
🇯🇵Kyoto, Japan
Shinshu University Hospital
🇯🇵Matsumoto, Japan
Nagasaki University Hospital
🇯🇵Nagasaki-shi, Japan
Nagoya University Hospital
🇯🇵Nagoya, Japan
Nagoya City University Hospital
🇯🇵Nagoya, Japan
Niigata University Medical And Dental Hospital
🇯🇵Niigata, Japan
Okayama University Hospital
🇯🇵Okayama, Japan
National Hospital Organization Okayama Medical Center
🇯🇵Okayama, Japan
Hokkaido University Hospital
🇯🇵Sapporo-shi, Japan
Sapporo Medical University Hospital
🇯🇵Sapporo, Japan
National Cerebral and Cardiovascular Center
🇯🇵Suita-Shi, Japan
Juntendo University Hospital
🇯🇵Tokyo, Japan
Fujita Health University Hospital
🇯🇵Toyoake, Japan
University of Tsukuba Hospital
🇯🇵Tsukuba City, Japan
Severance Hospital Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Hospital Pulau Pinang
🇲🇾George Town, Malaysia
Hospital Serdang
🇲🇾Kajang, Malaysia
Sarawak Heart Center
🇲🇾Kota Samarahan, Malaysia
Institut Jantung Negara (National Heart Institute)
🇲🇾Kuala Lumpur, Malaysia
Instituto Nacional de Cardiologia Dr. Ignacio Chavez
🇲🇽Ciudad De México, Mexico
Consultorio Privado del Dr. Gabriel Arturo Ramos Lopez
🇲🇽Guadalajara, Mexico
Operadora de Hospitales Angeles SA de CV Hospital Angeles Lomas
🇲🇽Mexico, Mexico
Hospital Universitario Dr Jose Eleuterio Gonzalez
🇲🇽Monterrey, Mexico
Unidad de Investigacion Clinica en Medicina S.C. (UDICEM)
🇲🇽Monterrey, Mexico
Centro de Investigacion Clinica Chapultepec
🇲🇽Morelia, Mexico
VUMC Amsterdam
🇳🇱Amsterdam, Netherlands
St. Antonius Ziekenhuis Nieuwegein
🇳🇱Nieuwegein, Netherlands
Radboud Umcn
🇳🇱Nijmegen, Netherlands
Erasmus MC
🇳🇱Rotterdam, Netherlands
Akershus Universitetssykehus
🇳🇴Nordbyhagen, Norway
Oslo University Hospital
🇳🇴Oslo, Norway
Szpital Uniwersytecki nr 2 im dr Jana Biziela w Bydgoszczy, Klinika Kardiologii
🇵🇱Bydgoszcz, Poland
Uniwersyteckie Centrum Kliniczne
🇵🇱Gdansk, Poland
Uniwersytecki Szpital Kliniczny nr 2 PUM w Szczecinie
🇵🇱Szczecin, Poland
Panstwowy Instytut Medyczny Ministerstwa Spraw Wewnetrznych i Administracji
🇵🇱Warszawa, Poland
Uls Coimbra - Hosp. Univ. Coimbra
🇵🇹Coimbra, Portugal
Uls Santa Maria - Hosp. Pulido Valente
🇵🇹Lisboa, Portugal
Uls Sao Jose - Hosp. Santa Marta
🇵🇹Lisbon, Portugal
Altay Regional Cardiological Dispensary
🇷🇺Barnaul, Russian Federation
Chelyabinsk Regional Clinical Hospital
🇷🇺Chelyabinsk, Russian Federation
State Autonomous HealthCare Institution 'Interregional Clinical Diagnostic Center'
🇷🇺Kazan, Russian Federation
Scientific and Research Institution of Cardiovascular Diseases Complex Problems
🇷🇺Kemerovo, Russian Federation
Moscow City Clinical Hospital No.51
🇷🇺Moscow, Russian Federation
National Medical Research Center of Cardiology of MoH of Russian Federation
🇷🇺Moscow, Russian Federation
National medical Research Center n.a. V.A.Almazov of MoH of Russian Federation
🇷🇺Saint-Petersburg, Russian Federation
Samara Regional Clinical Cardiological Dispensary
🇷🇺Samara, Russian Federation
State Autonomous Healthcare Institution of Tyumen Region 'Scientific and Practical Medical Center'
🇷🇺Tumen, Russian Federation
Volgograd Regional Clinical Cardiology Center
🇷🇺Volgograd, Russian Federation
King Faisal Specialist Hospital & Research Center
🇸🇦Riyadh, Saudi Arabia
King Fahad Medical City
🇸🇦Riyadh, Saudi Arabia
University Clinical Center of Serbia
🇷🇸Belgrade, Serbia
Institute for Pulmonary Disease of Vojvodina
🇷🇸Sremska Kamenica, Serbia
National University Heart Centre, Singapore
🇸🇬Singapore, Singapore
National Heart Centre (NHC) Singapore
🇸🇬Singapore, Singapore
Narodny ustav srdcovych a cievnych chorob
🇸🇰Bratislava, Slovakia
The Eastern Slovakia Institute of Cardiovascular Diseases
🇸🇰Kosice, Slovakia
Milpark Hospital
🇿🇦Johannesburg, South Africa
Dr Kalla
🇿🇦Lenasia, South Africa
Hosp Univ Vall D Hebron
🇪🇸Barcelona, Spain
Hosp. Del Mar
🇪🇸Barcelona, Spain
Hosp. Univ. 12 de Octubre
🇪🇸Madrid, Spain
Hosp. Univ. La Paz
🇪🇸Madrid, Spain
Hosp. Univ. Pta. de Hierro Majadahonda
🇪🇸Madrid, Spain
Hosp. Costa Del Sol
🇪🇸Malaga, Spain
Hosp Clinico Univ de Salamanca
🇪🇸Salamanca, Spain
Sahlgrenska Universitetsjukhuset
🇸🇪Goteborg, Sweden
Skanes universitetssjukhus
🇸🇪Lund, Sweden
National Cheng Kung University Hospital
🇨🇳Tainan, Taiwan
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
Mackay Memorial Hospital
🇨🇳Taipei, Taiwan
Taipei Veterans General Hospital
🇨🇳Taipei, Taiwan
Phramongkutklao Hospital and Medical College
🇹🇭Bangkok, Thailand
Ramathibodi Hospital Mahidol University
🇹🇭Bangkok, Thailand
Siriraj Hospital Mahidol University
🇹🇭Bangkok, Thailand
Maharaj Nakorn Chiang Mai hospital Faculty of Medicine
🇹🇭Chiang Mai, Thailand
Srinagarind Hospital, Khon Kaen University
🇹🇭Khon Kaen, Thailand
Songklanagarind hospital
🇹🇭Songkhla, Thailand
Adana City Hospital
🇹🇷Adana, Turkey
Cukurova University Medical Faculty
🇹🇷Adana, Turkey
Ankara Etlik Speciality Hospital
🇹🇷Ankara, Turkey
Hacettepe University Medical Faculty
🇹🇷Ankara, Turkey
Gazi University Medical Faculty
🇹🇷Ankara, Turkey
Ankara Bilkent Sehir Hastanesi
🇹🇷Ankara, Turkey
Akdeniz University Medical Faculty
🇹🇷Antalya, Turkey
Bursa Yuksek Ihtisas Training and Research Hospital
🇹🇷Bursa, Turkey
Pamukkale University Medical Faculty
🇹🇷Denizli, Turkey
Siyami Ersek Training and Research Hospital
🇹🇷Istanbul, Turkey
Marmara University Medical Faculty
🇹🇷Istanbul, Turkey
Ege University Medical Faculty
🇹🇷Izmir, Turkey
Tepecik Training and Research Hospital
🇹🇷Izmir, Turkey
Dokuz Eylul University Medical Faculty
🇹🇷Izmir, Turkey
Kartal Kosuyolu Yuksek Ihtisas Egitim Ve Arastirma Hastanesi
🇹🇷Kartal Istanbul, Turkey
Mersin University Medical Faculty
🇹🇷Mersin, Turkey
CNE 'Cherkasy Regional Cardiological Center of Cherkasy Regional Council'
🇺🇦Cherkassy, Ukraine
Communal Noncommercial Enterprise Cherkasy Regional Hospital of Cherkasy Regional Council
🇺🇦Cherkasy, Ukraine
MI 'Dnipropetrovsk Regional Clinical Center of Cardiology and Cardiac Surgery'
🇺🇦Dnipro, Ukraine
CNE' City Clinical Hospital #8' of Kharkiv City Council
🇺🇦Kharkiv, Ukraine
SI National Scientific Center Institute of Cardiology of M.D. Strazhesko of NAMS of Ukraine
🇺🇦Kyiv, Ukraine
State Institute Of Phthisiology And Pulmonology N.A. F.G. Yanovskiy Of Ams Ukraine
🇺🇦Kyiv, Ukraine
Communal Noncommercial Enterprise of Lviv Regional Council 'Lviv Regional Clinical Hospital'
🇺🇦Lviv, Ukraine
Municipal Non-commercial Enterprise Ternopil University Hospital of Ternopil Regional Council
🇺🇦Ternopil, Ukraine
Royal Free Hospital
🇬🇧London, United Kingdom
Freeman Hospital
🇬🇧Newcastle Upon Tyne, United Kingdom
Sheffield Teaching Hospitals NHS Foundation Trust Royal Hallamshire Hospital
🇬🇧Sheffield, United Kingdom
Hanoi Medical University Hospital
🇻🇳Hanoi, Vietnam
Cho Ray Hospital
🇻🇳Ho Chi Minh, Vietnam
Tam Anh Hospital
🇻🇳Ho Chi Minh, Vietnam
Tam Duc Heart Hospital
🇻🇳Ho Chi Minh, Vietnam
University Medical Center Ho Chi Minh city
🇻🇳Ho Chi Minh, Vietnam