Outcome Study Assessing a 75 Milligrams (mg) Dose of Macitentan in Patients With Pulmonary Arterial Hypertension

Pulmonary Arterial Hypertension Clinical Trial

— UNISUS  

Official title:

A Phase 3, Prospective, Multicenter, Double-blind, Double-dummy, Randomized, Active-controlled, Parallel-group, Group-sequential, Adaptive, Event-driven Study to Compare Efficacy, Safety, and Tolerability of Macitentan 75 mg Versus Macitentan 10 mg in Patients With Pulmonary Arterial Hypertension, Followed by an Open-label Treatment Period With Macitentan 75 mg

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04273945
• Other study ID #: CR108740
• Secondary ID: 2019-002533-11AC
• Status: Recruiting
• Phase: Phase 3
• Start date: June 30, 2020
• Est. completion date: February 20, 2029

Study information

• Verified date: June 2024
• Source: Actelion
• Contact: Study Contact
• Phone: 844-434-4210
• Email: Participate-In-This-Study[@]its.jnj.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 900
• Est. completion date: February 20, 2029
• Est. primary completion date: August 27, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Familial Primary Pulmonary Hypertension
• Hypertension
• Pulmonary Arterial Hypertension

Intervention

Drug:
• Macitentan 10 mg
Participants will receive macitentan 10 mg film-coated tablets orally.
• Macitentan 37.5 mg
Participants will receive macitentan 37.5 mg film-coated tablets orally.
• Macitentan 75 mg
Participants will receive macitentan 75 mg film-coated tablets orally.
• Placebo
Participants will receive matching placebo film-coated tablets orally.

Locations

Country	Name	City	State
Argentina	Sanatorio de la Trinidad Mitre	Buenos Aires
Argentina	Sanatorio Guemes	C.a.b.a.
Argentina	Centro Médico Dra. De Salvo	Caba
Argentina	Hospital Italiano de Buenos Aires	Caba
Argentina	Sanatorio Ramon Cereijo	Caba
Argentina	Instituto de Cardiologia de Corrientes	Corrientes
Argentina	Instituto Cardiovascular de Rosario	Rosario
Argentina	Instituto Medico de La Fundacion Estudios Clinicos	Rosario
Australia	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
Austria	LKH-Univ. Klinikum Graz	Graz
Austria	Ordensklinikum Linz GmbH Elisabethinen	Linz
Austria	Medical University Vienna	Vienna
Belarus	Minsk Regional Clinical Hospital	Minsk
Belarus	The Republican Scientific-Practical Center ''Cardiology''	Minsk
Belgium	ULB Hôpital Erasme	Brussels
Belgium	UZ Leuven	Leuven
Brazil	Instituto das Pequenas Missionárias de Maria Imaculada - Hospital Madre Teresa	Belo Horizonte
Brazil	Universidade Federal De Minas Gerais - Hospital das Clínicas	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	Hospital Das Clinicas Da Faculdade De Medicina Da USP	Sao Paulo
Brazil	Secretaria de Estado da Saude Instituto Dante Pazzanese de Cardiologia	Sao Paulo
Bulgaria	Multiprofile Hospital For Active Treatment National Cardiology Hospital, Ead	Sofia
Bulgaria	University Multiprofile Hospital for Active Treatment- UMHAT Sveta Anna AD	Sofia
Canada	St. Joseph's Health Centre	Hamilton	Ontario
Canada	Jewish General Hospital	Montreal	Quebec
Canada	University of Ottawa Heart Institute	Ottawa	Ontario
Canada	University Health Network - Toronto General Hospital	Toronto	Ontario
China	Beijing Anzhen Hospital	Beijing
China	Beijing Chaoyang 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	Renji Hospital	Shanghai
China	Shanghai Pulmonary Hospital	Shanghai
China	Zhongshan Hospital Fudan University	Shanghai
China	Shengjing Hospital Of China Medical University	Shenyang
China	The General Hospital of Northern Theater Command	Shenyang
China	Tianjin Medical University General Hospital	Tianjin
China	The First Affiliated Hospital of Xian Jiaotong University	Xi'An
Colombia	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
Czechia	General University Hospital II.department of Internal Medicine-cardiology and angiology	Praha 2
Denmark	Århus Universitetshospital, Skejby, Hjertemedicinsk Afdeling B	Arhus
France	CHU de Brest - Hopital de la Cavale Blanche	Brest
France	Hôpital Côte de Nacre	Caen Cedex
France	Hopital Bicêtre - Aphp Hôpitaux 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
Germany	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
Greece	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
Hungary	Gottsegen Gyorgy Orszagos Kardiovaszkularis Intezet Felnott kardiologiai osztaly	Budapest
Hungary	Semmelweis Egyetem,Pulmonológiai Klinika	Budapest
Hungary	Pecsi Tudomanyegyetem Altalanos Orvostudomanyi Kar	Pecs
Hungary	Szegedi Tudományegyetem, Általános Orvostudományi Kar, Családorvosi Intézet és rendelo	Szeged
India	Cims Hospital	Ahmedabad
India	NHL Medical College (SVP Hospital IMSR)	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
Israel	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
Italy	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
Japan	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	Kyoto University Hospital	Kyoto
Japan	University Hospital Kyoto Perfectural University of Medicine	Kyoto
Japan	Shinshu University Hospital	Matsumoto
Japan	Nagasaki University Hospital	Nagasaki-shi
Japan	Nagoya City University Hospital	Nagoya
Japan	Nagoya University Hospital	Nagoya
Japan	Niigata University Medical And Dental Hospital	Niigata
Japan	National Hospital Organization Okayama Medical Center	Okayama
Japan	Okayama University Hospital	Okayama
Japan	Sapporo Medical University Hospital	Sapporo
Japan	Hokkaido University Hospital	Sapporo-shi
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
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	Severance Hospital Yonsei University Health System	Seoul
Malaysia	Hospital Pulau Pinang	George Town
Malaysia	Hospital Serdang	Kajang
Malaysia	Sarawak Heart Center	Kota Samarahan, Kuching
Malaysia	Institut Jantung Negara (National Heart Institute)	Kuala Lumpur
Mexico	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
Netherlands	VUMC Amsterdam	Amsterdam
Netherlands	St. Antonius Ziekenhuis Nieuwegein	Nieuwegein
Netherlands	Radboud Umcn	Nijmegen
Netherlands	Erasmus MC	Rotterdam
Norway	Akershus Universitetssykehus	Nordbyhagen
Norway	Oslo University Hospital	Oslo
Poland	Uniwersytecki Szpital Kliniczny w Bialymstoku	Bialystok
Poland	Szpital Uniwersytecki nr 2 im dr Jana Biziela w Bydgoszczy, Klinika Kardiologii	Bydgoszcz
Poland	Uniwersyteckie Centrum Kliniczne	Gdansk
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	Uniwersytecki Szpital Kliniczny nr 2 PUM w Szczecinie	Szczecin
Poland	Panstwowy Instytut Medyczny Ministerstwa Spraw Wewnetrznych i Administracji	Warszawa
Poland	Wojewodzki Szpital Specjalist, Osrodek Badawczo-Rozwojowy	Wroclaw
Portugal	Centro Hospitalar e Universitário de Coimbra - Hospitais da Universidade de Coimbra	Coimbra
Portugal	Centro Hospitalar Lisboa Norte EPE - Hospital Pulido Valente	Lisboa
Portugal	Hospital De Santa Marta	Lisbon
Russian Federation	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
Saudi Arabia	King Fahad Medical City	Riyadh
Saudi Arabia	King Faisal Specialist Hospital & Research Center	Riyadh
Serbia	University Clinical Center of Serbia	Belgrade
Serbia	Institute for Pulmonary Disease of Vojvodina	Sremska Kamenica
Singapore	National Heart Centre (NHC) Singapore	Singapore
Singapore	National University Heart Centre, Singapore	Singapore
Slovakia	Narodny ustav srdcovych a cievnych chorob	Bratislava
Slovakia	The Eastern Slovakia Institute of Cardiovascular Diseases	Kosice
South Africa	Milpark Hospital	Johannesburg
South Africa	Dr Kalla	Lenasia
Spain	Hosp. Del Mar	Barcelona
Spain	Hosp. Univ. Vall D Hebron	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
Sweden	Sahlgrenska Universitetsjukhuset	Goteborg
Sweden	Skanes universitetssjukhus	Lund
Taiwan	National Cheng Kung University Hospital	Tainan
Taiwan	Mackay Memorial Hospital	Taipei
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Taipei Veterans General Hospital	Taipei
Thailand	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
Turkey	Adana City Hospital	Adana
Turkey	Cukurova University Medical Faculty	Adana
Turkey	Ankara Bilkent Sehir Hastanesi	Ankara
Turkey	Ankara Etlik Speciality Hospital	Ankara
Turkey	Gazi University Medical Faculty	Ankara
Turkey	Hacettepe University Medical Faculty	Ankara
Turkey	Akdeniz University Medical Faculty	Antalya
Turkey	Bursa Yuksek Ihtisas Training and Research Hospital	Bursa
Turkey	Pamukkale University Medical Faculty	Denizli
Turkey	Marmara University Medical Faculty	Istanbul
Turkey	Siyami Ersek Training and Research Hospital	Istanbul
Turkey	Dokuz Eylul University Medical Faculty	Izmir
Turkey	Ege University Medical Faculty	Izmir
Turkey	Tepecik Training and Research Hospital	Izmir
Turkey	Kartal Kosuyolu Yuksek Ihtisas Egitim Ve Arastirma Hastanesi	Kartal Istanbul
Turkey	Mersin University Medical Faculty	Mersin
Ukraine	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
United Kingdom	Royal Free Hospital	London
United Kingdom	Freeman Hospital	Newcastle Upon Tyne
United Kingdom	Sheffield Teaching Hospitals NHS Foundation Trust Royal Hallamshire Hospital	Sheffield
United States	AnMed Health	Anderson	South Carolina
United States	University of Michigan	Ann Arbor	Michigan
United States	Northside Hospital	Atlanta	Georgia
United States	Piedmont Healthcare	Austell	Georgia
United States	The Robert Larner, M.D. College of Medicine at The University of Vermont	Burlington	Vermont
United States	Lindner Clinical Trial Center/Christ Hospital	Cincinnati	Ohio
United States	UT Southwestern Medical Center	Dallas	Texas
United States	National Jewish Health	Denver	Colorado
United States	Duke	Durham	North Carolina
United States	Baylor College of Medicine (BCM) - Baylor Heart Clinic	Houston	Texas
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	Scripps Memorial Hospital	La Jolla	California
United States	USC Keck	Los Angeles	California
United States	Norton Pulmonary Specialists	Louisville	Kentucky
United States	University of Wisconsin Hospital and Clinics	Madison	Wisconsin
United States	Medical College Of Wisconsin	Milwaukee	Wisconsin
United States	Winthrop University Hospital	Mineola	New York
United States	Louisiana State University	New Orleans	Louisiana
United States	Columbia University	New York	New York
United States	Mount Sinai	New York	New York
United States	Advocate Christ Medical Center	Oak Lawn	Illinois
United States	Integris Baptist Office	Oklahoma City	Oklahoma
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Arizona Pulmonary Specialists, Ltd	Phoenix	Arizona
United States	Mayo Clinic	Phoenix	Arizona
United States	Allegheny General Hospital of Research	Pittsburgh	Pennsylvania
United States	Baylor Scott White - Plano	Plano	Texas
United States	Oregon Health And Science University	Portland	Oregon
United States	Oregon Pulmonary Clinic	Portland	Oregon
United States	The Oregon Clinic	Portland	Oregon
United States	Reno Heart Institute	Reno	Nevada
United States	Saint Louis University Academic Pavillion	Saint Louis	Missouri
United States	Washington University School Of Medicine	Saint Louis	Missouri
United States	San Antonio Methodist/TX Transplant Physicians Group	San Antonio	Texas
United States	Jeffrey S. Sager, MD Medical Corporation	Santa Barbara	California
United States	Stony Brook University Medical Center	Stony Brook	New York
United States	Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center	Torrance	California
United States	Troy Beaumont	Troy	Michigan
United States	Cleveland Clinic	Weston	Florida
United States	Lankenau Medical Center	Wynnewood	Pennsylvania
Vietnam	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

Sponsors (1)

Lead Sponsor	Collaborator
Actelion

Countries where clinical trial is conducted

United States,  Vietnam,  Argentina,  Australia,  Austria,  Belarus,  Belgium,  Brazil,  Bulgaria,  Canada,  China,  Colombia,  Czechia,  Denmark,  France,  Germany,  Greece,  Hungary,  India,  Israel,  Italy,  Japan,  Korea, Republic of,  Malaysia,  Mexico,  Netherlands,  Norway,  Poland,  Portugal,  Russian Federation,  Saudi Arabia,  Serbia,  Singapore,  Slovakia,  South Africa,  Spain,  Sweden,  Taiwan,  Thailand,  Turkey,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Double-blind Treatment Period: Time to First Clinical Events Committee (CEC)-adjudicated Morbidity or Mortality (M/M) Events	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.	Up to 4 years
Secondary	Double-blind Treatment Period: Change From Baseline to Week 24 in 6MWD	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.	Baseline up to Week 24
Secondary	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	Number of Participants with CEC-adjudicated death or hospitalization due to PAH will be reported.	Up to 4 years
Secondary	Double-blind Treatment Period: Change From Baseline to Week 24 in PAH Symptoms Based on PAH-SYMPACT Questionnaire- Cardiopulmonary Symptom Domain Score	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.	Baseline up to Week 24
Secondary	Double-blind Treatment Period: Change From Baseline to Week 24 in PAH Symptoms Based on PAH-SYMPACT Questionnaire- Cardiovascular Symptom Domain Score	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.	Baseline up to Week 24
Secondary	Double-blind Treatment Period: Time to Death Occurring Between Randomization and End of Double-blind Treatment (EDBT)	Time to death occurring between randomization and EDBT will be reported.	Up to 4 years
Secondary	Treatment Extension Period: Time to Death Occurring Between Randomization and End of Study (EOS)	Time to death occurring between randomization and EOS will be reported.	Up to 6 years