Clinical trial NCT03626688: A Study Evaluating the Efficacy and Safety of Ralinepag to Improve Treatment Outcomes in PAH Patients
Official title: A Phase 3, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Ralinepag When Added to PAH Standard of Care or PAH Specific Background Therapy in Subjects With WHO Group 1 PAH
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: PAH
Pulmonary Hypertension
Pulmonary Arterial Hypertension
Hypertension
Connective Tissue Diseases
Familial Primary Pulmonary Hypertension
Vascular Diseases
Cardiovascular Diseases
Hypertension, Pulmonary
Lung Diseases
Respiratory Tract Disease
Keywords: Prostacyclin
Connective Tissue Disease-Associated
6 Minute Walk Test
6 Minute Walk Distance
Pulmonary Vascular Resistance
Right Ventricular Function
Lead sponsor: United Therapeutics
Sponsor class: INDUSTRY
First posted: 2018-08-13
Enrollment: 1000
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Study ROR-PH-301, ADVANCE OUTCOMES, is designed to assess the efficacy and safety of ralinepag when added to pulmonary arterial hypertension (PAH) standard of care or PAH-specific background therapy in subjects with World Health Organization (WHO) Group 1 PAH.

Detailed description: Study ROR-PH-301 is a multicenter, randomized, double-blind, placebo-controlled study. Subjects who meet entry criteria will be randomly allocated 1:1 to receive ralinepag or placebo, in addition to their standard of care or PAH-specific background therapy, as applicable. The primary endpoint is the time (in days) from randomization to the first adjudicated protocol-defined clinical worsening event. All primary endpoint events will be adjudicated by an independent Clinical Event Committee (CEC) in a blinded fashion. Subjects who have a confirmed primary endpoint event adjudicated by the CEC at any time during the study and all subjects on treatment at the conclusion of the study who have completed the Week 28 Visit (after the target number of confirmed events is achieved) will have the option to enroll in an open-label extension (OLE) study. Subjects who do not choose to participate in the OLE study will discontinue study drug and should remain in the study for long-term follow-up of survival status and will receive standard of care PAH treatment, at the discretion of the treating physician.

Eligibility criteria: Inclusion Criteria:

1. At least 18 years of age.
2. Evidence of a personally signed and dated informed consent form indicating that the subject has been informed of all pertinent aspects of the study prior to initiation of any study-related procedures.
3. Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures
4. Primary diagnosis of symptomatic PAH.
5. Has had a right heart catheterization (RHC) performed at or within 3 years prior to Screening (RHC will be performed during Screening if not available) that is consistent with the diagnosis of PAH.
6. Has WHO/ NYHA functional class II to IV symptoms.
7. If on PAH-specific background oral therapy, subject is on stable therapy with either an endothelin receptor antagonist (ERA) and/or a phosphodiesterase type 5 inhibitor (PDE5-I) or a soluble guanylate cyclase (sGC) stimulator.
8. Has a 6MWD of ≥150 meters.
9. If taking concomitant medications that may affect the clinical manifestations of PAH (eg, calcium channel blockers, diuretics, digoxin, or L arginine supplementation, beta blockers, angiotensin-converting enzyme inhibitors, or angiotensin II receptor blockers), must be on a stable dose for at least 30 days prior to the Baseline Visit and the dosage maintained throughout the study. The exception is that the dose of diuretics must be stable for at least the 10 days prior to Baseline.
10. Both male and female subjects agree to use a highly effective method of birth control throughout the entire study period from informed consent through to the 30-Day Follow-up Visit, if the possibility of conception exists. Eligible male and female subjects must also agree not to participate in a conception process during the study and for 30 days after the last dose of IMP. Eligible male subjects must agree not to participate in sperm donation for 90 days after the last dose of IMP.

Exclusion Criteria:

1. For subjects with known HIV-associated PAH, a cluster designation 4 (CD4+) T-cell count \<200/mm3 within 90 days of Baseline.
2. Must not have 3 or more left ventricular dysfunction risk factors as defined in the study protocol.
3. Has evidence of more than mild lung disease on pulmonary function tests performed within 180 days prior to, or during Screening.
4. Has evidence of thromboembolic disease as determined by a V/Q lung scan or local standard of care diagnostic evaluation at or after diagnosis of PAH.
5. Current diagnosis of ongoing and clinically significant sleep apnea as defined by the Investigator.
6. Male subjects with a corrected QT interval using Fridericia's formula (QTcF) \>450 msec and female subjects with a QTcF \>470 msec on ECG recorded at Screening and analyzed by the central ECG laboratory. Subjects with evidence of intraventricular conduction delay, defined as a QRS interval greater than 110 msec, will be excluded if the QTcF is \>500 msec for both males and females.
7. Severe chronic liver disease (ie, Child-Pugh Class C), portal hypertension, cirrhosis or complications of cirrhosis/portal hypertension (eg, history of variceal hemorrhage, encephalopathy).
8. Confirmed active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV).
9. Subjects with alanine aminotransferase or aspartate aminotransferase ≥3 times the upper limit of normal (ULN) or total bilirubin ≥2 × ULN at Screening.
10. Chronic renal insufficiency as defined by serum creatinine \>2.5 mg/dL or requiring dialysis at Screening.
11. Hemoglobin concentration \<9 g/dL at Screening.
12. Subjects treated with an IV or SC prostacyclin pathway agent (eg, epoprostenol, treprostinil, or iloprost) or activin signaling inhibitor for PAH at any time prior to Baseline (use in vasoreactive testing is permitted).
13. Subjects currently on or who were treated with an inhaled or oral prostacyclin pathway agent (iloprost, treprostinil, beraprost, or selexipag) for \>6 months or within 90 days prior to Baseline.
14. Subject has pulmonary veno-occlusive disease.
15. Malignancy diagnosed and/or treated within 5 years prior to Screening, with the exception of localized non-metastatic basal cell or squamous cell carcinoma of the skin or in-situ carcinoma of the cervix excised with curative intent.
16. Subject tests positive for amphetamine, cocaine, methamphetamine, methylenedioxymethamphetamine or phencyclidine in urine drug screen performed at Screening, or has a recent history (6 months) of alcohol or drug abuse. A subject will not be excluded due to a positive drug screen caused by prescribed medications.
17. Initiation or discontinuation of a cardio-pulmonary rehabilitation program based upon exercise within 90 days prior to Screening and/or planned during study participation.
18. Prior participation in any study of ralinepag or participation in another interventional clinical study with medicinal products within 30 days prior to Screening. Concurrent participation in registry or observational studies is allowed, as long as the subject can fulfill all other entry criteria and comply with all study procedures.
19. Any reason that, in the opinion of the Investigator or Medical Monitor, precludes the subject from participating in the study (eg, any previous or intercurrent medical condition) that may increase the risk associated with study participation or that would confound study analysis or impair study participation or cooperation.
20. Known hypersensitivity to ralinepag or any of the excipients.
21. Life expectancy \<12 months based on the Investigator's opinion.
22. Women who are pregnant, lactating or breast-feeding.

Primary outcomes:
measure: Time from randomization to the first adjudicated protocol-defined clinical worsening event
timeFrame: The study duration was event-based. This parameter was assessed from randomization until the conclusion of the study, up to 3 years
Secondary outcomes:
measure: Change from Baseline in N-terminal pro-brain natriuretic peptide (NT-proBNP)
timeFrame: Baseline to Week 28
measure: Change from Baseline in 6-minute walk distance (6MWD)
timeFrame: Baseline to Week 28
measure: Change from Baseline in WHO/New York Heart Association (NYHA) Functional Class
timeFrame: Baseline to Week 28
measure: Shift and proportion of subjects who attain all 3 of the following: NT-proBNP level <300 pg/mL, 6MWD >440 meters, and WHO/NYHA Functional Class I or II
timeFrame: Baseline to Week 28
measure: Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL) risk score
timeFrame: Baseline to Week 28
measure: Clinical improvement as defined by the absence of clinical worsening and fulfillment of at least 2 of the 3 of the following: increase in 6MWD ≥10% or ≥30 m, improvement to or maintenance of WHO FC I or II, and decrease in NT-proBNP by at least 30%.
timeFrame: Baseline to Week 28
measure: Change from Baseline in health-related quality of life as measured by patient-reported outcomes.
timeFrame: Baseline to Week 28
measure: Time to first all-cause nonelective hospitalization
timeFrame: The study duration was event-based. This parameter was assessed from randomization until the conclusion of the study (when the target number of adjudicated events was achieved, as defined in the study protocol).
measure: Time to all-cause mortality
timeFrame: The study duration was event-based. This parameter was assessed from randomization until the conclusion of the study (when the target number of adjudicated events was achieved, as defined in the study protocol).
measure: Change from Baseline in heart rate recovery (HRR) following completion of the 6MWT
timeFrame: Baseline to Week 28
measure: Safety and tolerability of ralinepag in subjects with PAH
timeFrame: Baseline to Week 28
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Phoenix
country: United States
facility: St. Joseph's Hospital and Medical Center
state: Arizona
city: Scottsdale
country: United States
facility: Mayo Clinic Scottsdale
state: Arizona
city: Tucson
country: United States
facility: University of Arizona
state: Arizona
city: La Jolla
country: United States
facility: UCSD Health Sciences
state: California
city: Loma Linda
country: United States
facility: Loma Linda University Medical Center
state: California
city: Los Angeles
country: United States
facility: Ronald Reagan UCLA Medical Center
state: California
city: Los Angeles
country: United States
facility: Kaiser Permanente Los Angeles Medical Center
state: California
city: Los Angeles
country: United States
facility: Keck Hospital of USC
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Los Angeles
country: United States
facility: VA Greater Los Angeles Healthcare System
state: California
city: Orange
country: United States
facility: University of California, Irvine
state: California
city: Sacramento
country: United States
facility: University of California Davis Medical Center
state: California
city: Santa Barbara
country: United States
facility: SBPA Research LLC
state: California
city: Stanford
country: United States
facility: Stanford Healthcare
state: California
city: Torrance
country: United States
facility: LA Biomedical Research Institute Harbor-UCLA Medical Center
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital
state: Colorado
city: Denver
country: United States
facility: National Jewish Health
state: Colorado
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic Florida
state: Florida
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Orlando
country: United States
facility: Central Florida Pulmonary Group
state: Florida
city: Orlando
country: United States
facility: AdventHealth Orlando
state: Florida
city: Weston
country: United States
facility: Cleveland Clinic Florida
state: Florida
city: Atlanta
country: United States
facility: Emory University Hospital
state: Georgia
city: Austell
country: United States
facility: Piedmont Healthcare Pulmonary and Critical Care Research
state: Georgia
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: Elk Grove Village
country: United States
facility: Ascension Alexian Brothers
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University School of Medicine
state: Indiana
city: Indianapolis
country: United States
facility: Community Health Network Cancer Center North
state: Indiana
city: Indianapolis
country: United States
facility: St. Vincent Medical Group, Inc.
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Louisville
country: United States
facility: Kentuckiana Pulmonary Research Center
state: Kentucky
city: New Orleans
country: United States
facility: Ochsner Medical Center
state: Louisiana
city: South Portland
country: United States
facility: Chest Medicine Associates
state: Maine
city: Baltimore
country: United States
facility: University of Maryland Medical Center
state: Maryland
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Boston University Medical Center
state: Massachusetts
city: Grand Rapids
country: United States
facility: Spectrum Health Medical Group
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Omaha
country: United States
facility: Nebraska Medical Center
state: Nebraska
city: Albuquerque
country: United States
facility: University of New Mexico
state: New Mexico
city: Mineola
country: United States
facility: Winthrop Hospital
state: New York
city: New York
country: United States
facility: NYU Langone Medical Center
state: New York
city: New York
country: United States
facility: Weill-Cornell-New York Presbyterian Hospital
state: New York
city: New York
country: United States
facility: Mount Sinai School of Medicine
state: New York
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Greenville
country: United States
facility: East Carolina University
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati-Medical Science Building
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University Wexner Medical Center
state: Ohio
city: Oklahoma City
country: United States
facility: Integris Baptist Medical Center
state: Oklahoma
city: Portland
country: United States
facility: Oregon Clinic-Pulmonary West
state: Oregon
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: Temple University
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Allegheny General Hospital
state: Pennsylvania
city: Knoxville
country: United States
facility: Statcare Pulmonary Consultants
state: Tennessee
city: Austin
country: United States
facility: Ascension Texas Cardiovascular
state: Texas
city: Dallas
country: United States
facility: Baylor University Medical Center
state: Texas
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: Memorial Hermann Hospital
state: Texas
city: Houston
country: United States
facility: The Methodist Hospital Research Institute
state: Texas
city: Colchester
country: United States
facility: Vermont Lung Center
state: Vermont
city: Charlottesville
country: United States
facility: University of Virginia Medical Center
state: Virginia
city: Norfolk
country: United States
facility: Sentara Cardiovascular Research Institute
state: Virginia
city: Roanoke
country: United States
facility: Carilion Clinic Pulmonary and Sleep Medicine
state: Virginia
city: Milwaukee
country: United States
facility: Medical College of Wisconsin/Froedtert Hospital
state: Wisconsin
city: Ciudad Autonoma Buenos Aires
country: Argentina
facility: Hospital Italiano
state: Buenos Aires
city: Mar Del Plata
country: Argentina
facility: Instituto de Investigaciones Clinicas Mar del Plata
state: Buenos Aires
city: Rosario
country: Argentina
facility: Sanatorio Parque
state: Santa Fe
city: Buenos Aires
country: Argentina
facility: Sanatorio de la Trinidad Mitre
city: Caba
country: Argentina
facility: Cardiologia Palmero
city: Ciudad Autonoma Buenos Aires
country: Argentina
facility: Hospital Britanico de Buenos Aires
city: Ciudad Autonoma Buenos Aires
country: Argentina
facility: Fundacion Respirar
city: Ciudad Autonoma Buenos Aires
country: Argentina
facility: Fundacion Favaloro
city: Cordoba
country: Argentina
facility: Hospital Italiano de Cordoba
city: Cordoba
country: Argentina
facility: Hospital Privado Centro Medico de Cordoba S.A
city: Corrientes
country: Argentina
facility: Instituto de Cardiologia de Corrientes
city: Santa Fe
country: Argentina
facility: Hospital PROVINCIAL "Dr. Jose Maria Cullen"
city: Camperdown
country: Australia
facility: Royal Prince Alfred Hospital
state: New South Wales
city: Darlinghurst
country: Australia
facility: St Vincent's Hospital Sydney
state: New South Wales
city: Kingswood
country: Australia
facility: Nepean Hospital
state: New South Wales
city: Macquarie
country: Australia
facility: Macquarie University
state: New South Wales
city: Sydney
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Chermside
country: Australia
facility: The Prince Charles Hospital
state: Queensland
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Hobart
country: Australia
facility: Royal Hobart Hospital
state: Tasmania
city: Fitzroy
country: Australia
facility: St Vincent's Hospital Melbourne
state: Victoria
city: Melbourne
country: Australia
facility: The Alfred Hospital
state: Victoria
city: Murdoch
country: Australia
facility: Fiona Stanley Hospital
state: Western Australia
city: Innsbruck
country: Austria
facility: Medizinische Universität Innsbruck
city: Linz
country: Austria
facility: Ordensklinikum Linz GmbH - Elisabethinen, Fadingerstrasse 1
city: Vienna
country: Austria
facility: AKH Wien, Innere Med. II, Kardiologie, Währingergürtel 18-20
city: Bruxelles
country: Belgium
facility: Cliniques Universitaires de Bruxelles Hopital Erasme
city: Leuven
country: Belgium
facility: UZ Leuven, UZ Leuven Campus Gasthuisberg, Herestraat 49
city: Goiânia
country: Brazil
facility: HC-UFG - Hospital das Clínicas da Universidade Federal de Goiás
state: Goias
city: Belo Horizonte
country: Brazil
facility: Instituto das Pequenas Missionárias de Maria Imaculada - Hospital Madre Teresa
state: MG
city: Porto Alegre
country: Brazil
facility: Hospital Sao Lucas da PUC-RS
state: R.S
city: Porto Alegre
country: Brazil
facility: Irmandade da Santa Casa de Misericórdia de Porto Alegre
state: RS
city: Botucatu
country: Brazil
facility: UNESP-Faculdade de Medicina da Universidade Estadual Paulista Campus Botucatu
state: Sao Paulo
city: Sao Paulo
country: Brazil
facility: Hospital Sao Paulo
state: SP
city: Sao Paulo
country: Brazil
facility: Instituto do Coracao
state: SP
city: Sofia
country: Bulgaria
facility: MHAT - "National Heart Hospital" EAD, 65, Konyovitza Str.
city: Sofia
country: Bulgaria
facility: MHAT "Sveta Anna" Sofia AD
city: Calgary
country: Canada
facility: Peter Lougheed Centre
state: Alberta
city: London
country: Canada
facility: LHSC - Victoria Hospital
state: Ontario
city: Toronto
country: Canada
facility: University Health Network-Toronto General Hospital
state: Ontario
city: Montreal
country: Canada
facility: SMBD Jewish General Hospital d/b/a Jewish General Hospital
state: Quebec
city: Québec
country: Canada
facility: Institut Universitaire de Cardiologie et de Pneumologie de Quebec
state: Quebec
city: Providencia
country: Chile
facility: Instiuto Nacional del Torax
state: Santiago De Chile
city: Beijing
country: China
facility: Beijing Shijitan Hospital, Capital Medical University
state: Beijing
city: Guangzhou
country: China
facility: Guangdong Provincial People's Hospital
state: Guangdong
city: Changsha
country: China
facility: Xiangya Hospital Central South University
state: Hunan
city: Shanghai
country: China
facility: Shanghai Pulmonary Hospital
state: Shanghai
city: Beijing
country: China
facility: Fuwai Hospital, Chinese Academy of Medical Sciences
city: Zhengzhou
country: China
facility: Fuwai Central China Cardiovascular Hospital
city: Zagreb
country: Croatia
facility: Clinical Hospital Dubrava Zagreb, Avenija G.Šuška 6
city: Zagreb
country: Croatia
facility: University Clinic for Pulmonary Diseases, Jordanovac 104
city: Praha 2
country: Czechia
facility: Vseobecna fakultni nemocnice v Praze, II. interni klinika kardiologie a angiologie VFN a 1. LF UK, U nemocnice 2
city: Copenhagen
country: Denmark
facility: Copenhagen University Hospital (Rigshospitalet)
city: Århus
country: Denmark
facility: Århus Universitetshospital
city: Strasbourg
country: France
facility: CHU de Strasbourg - Nouvel Hôpital Civil, Ctre de competence Hypertension Arterielle Pulmona, 1 place de l Hopital
state: Bas Rhin
city: Grenoble
country: France
facility: CHU de Grenoble - Hôpital Albert Michallon, Clinique de Cardiologie, Boulevrad de la Chantourne
state: Isere
city: Saint-Étienne
country: France
facility: CHU de Saint-Etienne - Hopital Nord, Service de Medecine vasculaire et therapeutique, 81 Avenue A. Raimond
state: Loire
city: Vandoeuvre les Nancy
country: France
facility: CHU Nancy - Hôpital de Brabois Adultes, Pneumologie- Oncologie Médicale, Rue du Morvan
state: Meurthe Et Moselle
city: Bron cedex
country: France
facility: CHU Lyon - Hôpital Cardio-Vasculaire et Pneumologique Louis Pradel, Service de Pneumologie, 59 Boulevard Pinel
state: Rhone
city: Rouen cedex
country: France
facility: CHU de Rouen - Hôpital Charles Nicolle
state: Seine Maritime
city: Le Kremlin-Bicêtre
country: France
facility: Groupement Hospitalier Sud - Hôpital Bicêtre
state: Val De Marne
city: Besançon Cedex
country: France
facility: CHU Besançon - Hôpital Jean Minjoz
city: Brest cedex 2
country: France
facility: CHU de Brest - Hôpital de la Cavale Blanche
city: Lille Cedex
country: France
facility: CHRU de Lille - Hopital Cardiologique
city: Marseille
country: France
facility: Hôpital Nord - CHU Marseille
city: Heidelberg
country: Germany
facility: Thoraxklinik-Heidelberg Zentrum für Pulmonale Hypertonie
state: Baden-Württemberg
city: Greifswald
country: Germany
facility: Universitätsmedizin Greifswald
state: Mecklenburg-Vorpommern
city: Mainz
country: Germany
facility: Universitaetsmedizin der Johannes-Gutenberg-Universitaet Mainz, Zentrum für Kardiologie I, Centrum für Thrombose und Hämostase (CTH), Langenbeckstrasse 1
state: Rheinland Pfalz
city: Homburg
country: Germany
facility: Universitaetsklinikum des Saarlandes, Innere Medizin V, IMED, Kirrberger Strasse 100, Gebäude 41
state: Saarland
city: Leipzig
country: Germany
facility: Universitätsklinikum Leipzig, Medizinische Klinik II, Pneumologie
state: Sachsen
city: Donaueschingen
country: Germany
facility: Schwarzwald-Baar Klinikum
city: Dresden
country: Germany
facility: Universitaetsklinikum Carl Gustav Carus TU Dresden
city: Hamburg
country: Germany
facility: Universitaetsklinikum Hamburg-Eppendorf
city: Athens
country: Greece
facility: "Onasseio" Cardiosurgery Hospital, Hemodynamic Research and Interventional Cardiology Dept., 356, Syggrou Avenue
state: Kallithea
city: Alexandroupolis
country: Greece
facility: University General Hospital of Alexandroupolis
city: Chaidari
country: Greece
facility: University General Hospital Attikon
city: Thessaloniki
country: Greece
facility: AHEPA General Hospital of Thessaloniki, A' Cardiology Clinic, 1 St. Kyriakidi Street
city: Szeged
country: Hungary
facility: Szegedi Tudományegyetem Szent-Györgyi Albert Klinikai Központ Családorvosi Intézet és Rendelő
state: Csongrád-Csanád
city: Budapest
country: Hungary
facility: Gottsegen György Országos Kardiovaszkuláris Intézet
city: Pecs
country: Hungary
facility: Pecsi Tudomanyegyetem, Szivgyogyaszati Klinika, Ifjusag u. 13.
city: Haifa
country: Israel
facility: The Lady Davis Carmel Medical Center, 7 Michal st.
city: Jerusalem
country: Israel
facility: Hadassah Ein Kerem Medical Center, Kiryat Hadassah
city: Kfar- Sava
country: Israel
facility: Meir Medical Center, 59 Tshernichovski st.
city: Petach Tikva
country: Israel
facility: Rabin Medical Center-Beilinson Campus, Pulmonary Institute, 39 Jabotinsky St Ground floor
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center, 6 Weizmann St.
city: Palermo
country: Italy
facility: Istituto Mediterraneo Trapianti e Terapie a Alta Specializzazione (IRCCS-ISMETT)
state: PA
city: Foggia
country: Italy
facility: Azienda Ospedaliero Universitaria Ospedali Riuniti di Foggia, S.C. di Cardiologia, Viale Luigi Pinto, 1
city: Genova
country: Italy
facility: IRCC Ospedale Policlinico San Martino
city: Milano
country: Italy
facility: Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico, Via Francesco Sforza 35
city: Monza
country: Italy
facility: Azienda Socio Sanitaria Territoriale di Monza (Presidio San Gerardo)
city: Pavia
country: Italy
facility: Fondazione IRCCS Policlinico San Matteo
city: Roma
country: Italy
facility: Azienda Ospedaliera Universitaria Policlinico Umberto I - Università di Roma La Sapienza, Viale del Policlinico, 155
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
state: Gangnam-gu
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
state: Jongno-gu
city: Incheon
country: Korea, Republic of
facility: Gachon University Hospital Gil Medical Center
state: Namdong-gu
city: Mexico
country: Mexico
facility: Instituto Nacional de Cardiologia Dr Ignacio Chavez Rivera
state: Distrito Federal
city: Mexico
country: Mexico
facility: Instituto Nacional de Ciencias Médicas y Nutricion Dr. Salvador Zubiran
state: Distrito Federal
city: Guadalajara
country: Mexico
facility: CICUM San Miguel
state: Jalisco
city: Monterrey
country: Mexico
facility: Unidad de Investigacion Clinica en Medicina, S.C.
state: N.l.
city: Amsterdam
country: Netherlands
facility: VU Medisch Centrum, De Boelelaan 1117
city: Bialystok
country: Poland
facility: Uniwersytecki Szpital Kliniczny w Bialymstoku, Klinika Kardiologii z Oddzialem Intensywnego Nazdoru Kardiologicznego, M. Sklodowskiej 24a
city: Krakow
country: Poland
facility: Krakowski Szpital Specjalistyczny im. Jana Pawla II, Oddział Kliniczny Chorób Serca i Naczyń z Pododdziałem Intensywnego Nadzoru Kardiologicznego, Pradnicka 80
city: Otwock
country: Poland
facility: NZOZ Europejskie Centrum Zdrowia, ul. Borowa 14/18
city: Poznan
country: Poland
facility: Szpital Kliniczny Przemienienia Panskiego Uniwersytetu Medycznego im. Karola Marcinkowskiego w Poznaniu, Oddzial Kardiologii - F, ul. Dluga 1/2
city: Wroclaw
country: Poland
facility: Premium Clinic Wrocław CM, Podwale 83/17
city: Almada
country: Portugal
facility: Hospital Garcia de Orta, E.P.E
city: Coimbra
country: Portugal
facility: Centro Hospitalar e Universitário de Coimbra, E.P.E.
city: Lisboa
country: Portugal
facility: Centro Hospitalar Universitário Lisboa Norte, E.P.E. Hospital Pulido Valente
city: Porto
country: Portugal
facility: Centro Hospitalar de Santo António E.P.E.
city: Bucharest
country: Romania
facility: Institutul de Urgenta pentru Boli Cardiovasculare "Prof. Dr. C.C. Iliescu", Sos. Fundeni nr. 258
city: Bucuresti
country: Romania
facility: Institutul de Pneumoftiziologie "Marius Nasta", Sos. Viilor nr. 90, Sector 5
city: Cluj-Napoca
country: Romania
facility: Institutul Inimii "Niculae Stancioiu" Cluj-Napoca, Cardiologie, Str. Motilor nr. 19-21
city: Timisoara
country: Romania
facility: Spitalul Clinic de Boli Infectioase si Pneumoftiziologie "Dr. Victor Babes" Timisoara, Str. Gheorghe Adam nr. 13
city: Belgrade
country: Serbia
facility: Clinical Center of Serbia, Koste Todorovica 8
city: Belgrade
country: Serbia
facility: Clinical Center Zemun. Clinic for internal medicine, Department of Cardiology
city: Sremska Kamenica
country: Serbia
facility: Institute for Pulmonary Diseases of Vojvodina, Put Dr Goldmana 4
city: Singapore
country: Singapore
facility: National University Hospital
city: Singapore
country: Singapore
facility: National Heart Centre
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron, Respiratory Dept., Passeig Vall d'Hebron,119-129, Neumologia
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona, C/ Villarroel, 170
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Valencia
country: Spain
facility: Hospoital Universitari i Politecnic La Fe
city: Göteborg
country: Sweden
facility: Sahlgrenska Universitetssjukhuset
city: Linköping
country: Sweden
facility: Linköping Universitetssjukhuset
city: Umeå
country: Sweden
facility: Norrlands Universitetssjukhus, Hjärtcentrum
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Eskişehir
country: Turkey
facility: Osmangazi Uni Medical Faculty
state: Odunpazari
city: Adana
country: Turkey
facility: Balcalı, Çukurova Üniversitesi Kardiyoloji ABD
state: Saricam
city: Mersin
country: Turkey
facility: Mersin Üniversitesi Tip Fakültesi Ciftlikköy Kampüsü
state: Yenisehir
city: Ankara
country: Turkey
facility: Gazi University Medical Faculty Hospital
city: Bursa
country: Turkey
facility: Uludag Universitesi Tip Fakültesi, Gorukle Kampusu
city: Istanbul
country: Turkey
facility: Marmara Universitesi Istanbul Pendik Egitim ve Arastirma Hastanesi
city: Izmir
country: Turkey
facility: Dokuz Eylul Universitesi Tip Fakultesi, Mithatpasa caddesi Inciralti Balcova
city: Dnipro
country: Ukraine
facility: CE Dniprop RCC&C Center of Dniprop RC Dept of Card SI DMA of MOHU, Chair of Internal Medicine 3, 28, Knyazya Volodymyra Velykogo St.
city: Kyiv
country: Ukraine
facility: SI F.H.Yanovskyi National Institute of Phthisiology and Pulmonology of NAMSU, Clinical and Functional Dept, 10, Amosova St.
city: Lviv
country: Ukraine
facility: Communal Noncommercial Enterprise of Lviv Regional Council Lviv Clinical Hospital, Dept of Cardiology, D.Halytskyi Lviv NMU, Ch of Internal Medicine #1, 7, Chernihivska str.
city: London
country: United Kingdom
facility: Royal Free London NHS Foundation Trust, Pond Street
state: Greater London
city: Newcastle Upon Tyne
country: United Kingdom
facility: The Newcastle upon Tyne Hospitals NHS Foundation Trust, Sir William Leech Lung Research Centre
state: Tyne And Wear
city: Glasgow
country: United Kingdom
facility: Golden Jubilee National Hospital
state: West Dunbartonshire
city: London
country: United Kingdom
facility: Royal Brompton Hospital
city: London
country: United Kingdom
facility: Imperial College Healthcare NHS Trust
Study officials:
References: