Outcome Study Assessing a 75 Milligrams (mg) Dose of Macitentan in Patients With Pulmonary Arterial Hypertension (UNISUS)
Pulmonary Arterial Hypertension
About this trial
This is an interventional treatment trial for Pulmonary Arterial Hypertension
Eligibility Criteria
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 and maximum distance of 440 meters at screening
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
Sites / Locations
- Arizona Pulmonary Specialists, LtdRecruiting
- Mayo ClinicRecruiting
- Scripps Memorial HospitalRecruiting
- USC KeckRecruiting
- Jeffrey S. Sager, MD Medical CorporationRecruiting
- Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical CenterRecruiting
- National Jewish HealthRecruiting
- Cleveland ClinicRecruiting
- Northside HospitalRecruiting
- Piedmont HealthcareRecruiting
- Advocate Christ Medical CenterRecruiting
- Indiana University
- St. Vincent Medical Group, Inc.Recruiting
- University Of Iowa - Hospitals & ClinicsRecruiting
- Norton Pulmonary SpecialistsRecruiting
- Louisiana State UniversityRecruiting
- University of MichiganRecruiting
- Troy BeaumontRecruiting
- Washington University School of MedicineRecruiting
- Saint Louis University Academic PavillionRecruiting
- University of Nebraska Medical CenterRecruiting
- Reno Heart InstituteRecruiting
- Winthrop University HospitalRecruiting
- Mount SinaiRecruiting
- Columbia UniversityRecruiting
- Stony Brook University Medical CenterRecruiting
- DukeRecruiting
- Lindner Clinical Trial Center/Christ HospitalRecruiting
- Integris Baptist OfficeRecruiting
- The Oregon ClinicRecruiting
- Oregon Pulmonary ClinicRecruiting
- Oregon Health & Science UniversityRecruiting
- University of PennsylvaniaRecruiting
- Allegheny General Hospital of ResearchRecruiting
- Lankenau Medical Center
- AnMed HealthRecruiting
- UT Southwestern Medical CenterRecruiting
- Baylor College of Medicine (BCM) - Baylor Heart ClinicRecruiting
- Baylor Scott White - PlanoRecruiting
- San Antonio Methodist/TX Transplant Physicians GroupRecruiting
- The Robert Larner, M.D. College of Medicine at The University of VermontRecruiting
- University of Wisconsin Hospital and ClinicsRecruiting
- Medical College Of WisconsinRecruiting
- Sanatorio de la Trinidad MitreRecruiting
- Sanatorio GuemesRecruiting
- Hospital Italiano de Buenos AiresRecruiting
- Sanatorio Ramon Cereijo
- Centro Médico Dra. De SalvoRecruiting
- Instituto de Cardiologia de CorrientesRecruiting
- Instituto Medico de La Fundacion Estudios ClinicosRecruiting
- Instituto Cardiovascular de RosarioRecruiting
- Flinders Medical CentreRecruiting
- Royal Prince Alfred HospitalRecruiting
- The Prince Charles HospitalRecruiting
- St Vincent's hospitalRecruiting
- Royal Hobart HospitalRecruiting
- Fiona Stanley HospitalRecruiting
- Westmead HospitalRecruiting
- LKH-Univ. Klinikum GrazRecruiting
- Ordensklinikum Linz GmbH ElisabethinenRecruiting
- Medical University ViennaRecruiting
- The Republican Scientific-Practical Center ''Cardiology''
- Minsk Regional Clinical Hospital
- ULB Hôpital ErasmeRecruiting
- UZ LeuvenRecruiting
- Universidade Federal De Minas Gerais - Hospital das ClínicasRecruiting
- Instituto das Pequenas Missionárias de Maria Imaculada - Hospital Madre TeresaRecruiting
- Ceti - Centro de Estudos Em Terapias InovadorasRecruiting
- Ynova Pesquisa ClinicaRecruiting
- Universidade Federal de Goias - Hospital das Clinicas da UFGRecruiting
- Hospital das Clinicas de Porto AlegreRecruiting
- Instituto de Medicina Integral Professor Fernando FigueiraRecruiting
- Fundacao do ABC - Centro Universitario FMABCRecruiting
- Secretaria de Estado da Saúde - Instituto Dante Pazzanese de CardiologiaRecruiting
- Hospital Das Clinicas Da Faculdade De Medicina Da USPRecruiting
- Multiprofile Hospital For Active Treatment National Cardiology Hospital, EadRecruiting
- University Multiprofile Hospital for Active Treatment- UMHAT Sveta Anna ADRecruiting
- St. Joseph's Health CentreRecruiting
- University of Ottawa Heart InstituteRecruiting
- University Health Network - Toronto General HospitalRecruiting
- Jewish General HospitalRecruiting
- Beijing Chaoyang HospitalRecruiting
- Beijing Anzhen HospitalRecruiting
- Peking Union Medical College HospitalRecruiting
- The Second Xiangya Hospital of Central South HospitalRecruiting
- West China Hospital, Sichuan UniversityRecruiting
- The First Affiliated Hospital of Chongqing Medical UniversityRecruiting
- The First Affiliated Hospital of Guangzhou Medical UniversityRecruiting
- Shanghai Pulmonary HospitalRecruiting
- Renji HospitalRecruiting
- Zhongshan Hospital,Fudan UniversityRecruiting
- The General Hospital of Northern Theater CommandRecruiting
- Shengjing Hospital of China Medical UniversityRecruiting
- Tianjin Medical University General HospitalRecruiting
- The First Affiliated Hospital of Xi'an Jiaotong UniversityRecruiting
- Fundacion Neumologica ColombianaRecruiting
- Fundacion Cardiovascular de ColombiaRecruiting
- Clínica Imbanaco S.A.S.Recruiting
- Centro Cardiovascular Colombiano Clínica Santa MaríaRecruiting
- Hospital Universidad del NorteRecruiting
- General University Hospital II.department of Internal Medicine-cardiology and angiologyRecruiting
- Århus Universitetshospital, Skejby, Hjertemedicinsk Afdeling BRecruiting
- CHU de Brest - Hôpital de la Cavale Blanche
- Hôpital Côte de NacreRecruiting
- Hopital Bicêtre - Aphp Hôpitaux Universitaires Paris-SudRecruiting
- CHRU de Lille - Hopital Claude Huriez
- Aphm - Hopital Nord
- Centre Hospitalier Universitaire - de Nice - Hopital PasteurRecruiting
- CHU Saint-Etienne - Hôpital NordRecruiting
- Hopital Larrey CHU de ToulouseRecruiting
- Ruhr-Universität Bochum / Diabeteszentrum
- Medizinische Hochschule HannoverRecruiting
- Medizinische Klinik und Poliklinik V Klinikum Grosshadern der LMURecruiting
- Universitaetsklinikum RegensburgRecruiting
- University Hospital of AlexandroupolisRecruiting
- Alexandra General Hospital of AthensRecruiting
- University Hospital Of LarissaRecruiting
- Ahepa University General Hospital of ThessalonikiRecruiting
- Semmelweis Egyetem,Pulmonológiai KlinikaRecruiting
- Gottsegen György Országos Kardiológiai Intézet, Felnőtt kardiológiai osztályRecruiting
- Pecsi Tudomanyegyetem Klinikai KozpontRecruiting
- Szegedi Tudományegyetem, Általános Orvostudományi Kar, Családorvosi Intézet és rendelőRecruiting
- NHL Medical College (SVP Hospital IMSR)Recruiting
- Cims HospitalRecruiting
- Narayana Hrudayalaya LimitedRecruiting
- SRM Medical College Hospital & Research CentreRecruiting
- Govindaswamy Kuppuswamy Naidu Memorial HospitalRecruiting
- HealthWorld HospitalsRecruiting
- Care HospitalsRecruiting
- Rabindranath Tagore International Institute of Cardiac SciencesRecruiting
- GB Pant Institute of Post Graduate Medical Education & ResearchRecruiting
- Sir Ganga Ram HospitalRecruiting
- B.D. Mehta Mahavir Heart InstituteRecruiting
- Carmel Medical Center
- Shaare Zedek Medical CenterRecruiting
- Kaplan Medical CenterRecruiting
- The Chaim Sheba Medical CenterRecruiting
- Yitzhak Shamir Medical CenterRecruiting
- ASST Grande Ospedale Metropolitano NiguardaRecruiting
- AOU Di Modena, Policlinico Di ModenaRecruiting
- Ospedale San Francesco
- Fondazione IRCCS Policlinico San MatteoRecruiting
- Fondazione Toscana Gabriele Monasterio CNRRecruiting
- Policlinico Gemelli Universita CattolicaRecruiting
- The University of Tokyo HospitalRecruiting
- Kyushu University HospitalRecruiting
- Kure Kyosai HospitalRecruiting
- Kagoshima University HospitalRecruiting
- St.Marianna University HospitalRecruiting
- Kanazawa University HospitalRecruiting
- Kobe University HospitalRecruiting
- Kurume University HospitalRecruiting
- University Hospital Kyoto Perfectural University of MedicineRecruiting
- Kyoto University HospitalRecruiting
- Shinshu University HospitalRecruiting
- Nagasaki University HospitalRecruiting
- Nagoya University HospitalRecruiting
- Nagoya City University HospitalRecruiting
- Niigata University Medical & Dental HospitalRecruiting
- Okayama University HospitalRecruiting
- National Hospital Organization Okayama Medical CenterRecruiting
- Hokkaido University HospitalRecruiting
- Sapporo Medical University HospitalRecruiting
- National Cerebral and Cardiovascular CenterRecruiting
- Juntendo University HospitalRecruiting
- Fujita Health University HospitalRecruiting
- University of Tsukuba HospitalRecruiting
- Severance Hospital, Yonsei University Health SystemRecruiting
- Asan Medical CenterRecruiting
- Samsung Medical CenterRecruiting
- Seoul National University HospitalRecruiting
- Hospital Pulau PinangRecruiting
- Hospital SerdangRecruiting
- Sarawak Heart CenterRecruiting
- Institut Jantung Negara (National Heart Institute)Recruiting
- Instituto Nacional de Cardiologia Dr. Ignacio ChavezRecruiting
- Consultorio Privado del Dr. Gabriel Arturo Ramos LopezRecruiting
- Operadora de Hospitales Angeles SA de CV Hospital Angeles LomasRecruiting
- Hospital Universitario 'Dr. Jose Eleuterio Gonzalez'Recruiting
- Unidad de Investigacion Clinica en Medicina S.C. (UDICEM)Recruiting
- Centro de Investigacion Clinica ChapultepecRecruiting
- VUMC AmsterdamRecruiting
- St. Antonius Ziekenhuis NieuwegeinRecruiting
- Radboud UmcnRecruiting
- Erasmus MC
- Akershus Universitetssykehus
- Oslo University Hospital
- Uniwersytecki Szpital Kliniczny w BiałymstokuRecruiting
- Szpital Uniwersytecki nr 2 im dr Jana Biziela w Bydgoszczy, Klinika Kardiologii
- Uniwersyteckie Centrum KliniczneRecruiting
- SPSK nr 7 SUM w Katowicach Gornoslaskie Centrum Medyczne im. Prof. Leszka GiecaRecruiting
- Krakowski Szpital Specjalityczny im. Jana Pawla II, Oddzial Kliniczny Chorob Serca i NaczynRecruiting
- Samodzielny Publiczny Szpital Kliniczny nr 2 PUMRecruiting
- Centralny Szpital Kliniczny MSWiA w WarszawieRecruiting
- Wojewodzki Szpital Specjalist, Osrodek Badawczo-Rozwojowy
- Centro Hospitalar e Universitário de Coimbra - Hospitais da Universidade de CoimbraRecruiting
- Centro Hospitalar Lisboa Norte EPE - Hospital Pulido ValenteRecruiting
- Hospital De Santa MartaRecruiting
- Altay Regional Cardiological Dispensary
- Chelyabinsk Regional Clinical Hospital
- State Autonomous HealthCare Institution 'Interregional Clinical Diagnostic Center'
- Scientific and Research Institution of Cardiovascular Diseases Complex Problems
- Moscow City Clinical Hospital No.51
- National Medical Research Center of Cardiology of MoH of Russian Federation
- National medical Research Center n.a. V.A.Almazov of MoH of Russian Federation
- Samara Regional Clinical Cardiological Dispensary
- State Autonomous Healthcare Institution of Tyumen Region 'Scientific and Practical Medical Center'
- Volgograd Regional Clinical Cardiology Center
- King Faisal Specialist Hospital & Research CenterRecruiting
- King Fahad Medical CityRecruiting
- University Clinical Center of SerbiaRecruiting
- Institute for Pulmonary Disease of VojvodinaRecruiting
- National University Heart Centre, SingaporeRecruiting
- National Heart Centre (NHC) SingaporeRecruiting
- Narodny ustav srdcovych a cievnych chorobRecruiting
- The Eastern Slovakia Institute of Cardiovascular DiseasesRecruiting
- Milpark HospitalRecruiting
- Dr KallaRecruiting
- Hosp. Univ. Vall D HebronRecruiting
- Hosp. Del Mar
- Hosp. Univ. 12 de OctubreRecruiting
- Hosp. Univ. La PazRecruiting
- Hosp. Univ. Pta. de Hierro MajadahondaRecruiting
- Hosp. Costa Del SolRecruiting
- Hosp. Clinico Univ. de SalamancaRecruiting
- Sahlgrenska UniversitetsjukhusetRecruiting
- Skanes universitetssjukhusRecruiting
- National Cheng Kung University HospitalRecruiting
- National Taiwan University HospitalRecruiting
- Mackay Memorial HospitalRecruiting
- Taipei Veterans General HospitalRecruiting
- Phramongkutklao Hospital and Medical CollegeRecruiting
- Ramathibodi Hospital, Mahidol UniversityRecruiting
- Siriraj Hospital Mahidol UniversityRecruiting
- Maharaj Nakorn Chiang Mai hospital - Faculty of MedicineRecruiting
- Srinagarind Hospital, Khon Kaen UniversityRecruiting
- Songklanagarind hospitalRecruiting
- Adana City HospitalRecruiting
- Cukurova University Medical Faculty
- Hacettepe University Medical FacultyRecruiting
- Gazi University Medical FacultyRecruiting
- Ankara Bilkent Sehir HastanesiRecruiting
- Akdeniz University Medical FacultyRecruiting
- Bursa Yuksek Ihtisas Training and Research HospitalRecruiting
- Pamukkale University Medical FacultyRecruiting
- Siyami Ersek Training and Research HospitalRecruiting
- Marmara University Medical FacultyRecruiting
- Ege University Medical FacultyRecruiting
- Tepecik Training and Research HospitalRecruiting
- Dokuz Eylul University Medical FacultyRecruiting
- Kartal Kosuyolu Yuksek Ihtisas Egitim Ve Arastirma HastanesiRecruiting
- Mersin University Medical FacultyRecruiting
- CNE 'Cherkasy Regional Cardiological Center of Cherkasy Regional Council'
- Communal Noncommercial Enterprise Cherkasy Regional Hospital of Cherkasy Regional Council
- MI 'Dnipropetrovsk Regional Clinical Center of Cardiology and Cardiac Surgery'
- CNE' City Clinical Hospital #8' of Kharkiv City Council
- SI National Scientific Center Institute of Cardiology of M.D. Strazhesko of NAMS of Ukraine
- State Institute Of Phthisiology And Pulmonology N.A. F.G. Yanovskiy Of Ams Ukraine
- Communal Noncommercial Enterprise of Lviv Regional Council 'Lviv Regional Clinical Hospital'
- Municipal Non-commercial Enterprise Ternopil University Hospital of Ternopil Regional Council
- Royal Free HospitalRecruiting
- Freeman HospitalRecruiting
- Sheffield Teaching Hospitals NHS Foundation Trust Royal Hallamshire HospitalRecruiting
- Hanoi Medical University HospitalRecruiting
- Cho Ray HospitalRecruiting
- Tam Anh HospitalRecruiting
- Tam Duc Heart HospitalRecruiting
- University Medical Center Ho Chi Minh cityRecruiting
Arms of the Study
Arm 1
Arm 2
Active Comparator
Experimental
Macitentan 10 milligrams (mg) + Placebo
Macitentan 75 mg + 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.
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.