Pulmonary Arterial HypertensionPhase 3UNISUSNCT04273945
Outcome Study Assessing a 75 Milligrams (mg) Dose of Macitentan in Patients With Pulmonary Arterial Hypertension
A Phase 3 study testing Macitentan 10 mg, Macitentan 37.5 mg and Macitentan 75 mg in people with Pulmonary Arterial Hypertension, run by Actelion at 274 sites in 42 countries.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pulmonary Arterial Hypertension
- What is being tested?
- Macitentan 10 mg, Macitentan 37.5 mg and Macitentan 75 mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 935 participants
- Where
- 274 sitesin 42 countries
- Study dates
- 30 Jun 2020to 20 Feb 2029
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
274 sites in 42 countries.
274 sites in 42 countries
United States43 sites
AnMed Health
Anderson, South Carolina, 29621
University of Michigan
Ann Arbor, Michigan, 48109-5000
Piedmont Healthcare
Atlanta, Georgia, 30309
Northside Hospital
Atlanta, Georgia, 30342
The Oregon Clinic Pulmonary West
Beaverton, Oregon, 97008
The Robert Larner, M.D. College of Medicine at The University of Vermont
Burlington, Vermont, 05405
Lindner Clinical Trial Center/Christ Hospital
Cincinnati, Ohio, 45219
UT Southwestern Medical Center
Dallas, Texas, 75390
National Jewish Health
Denver, Colorado, 80206
Duke
Durham, North Carolina, 27710-4000
Baylor College of Medicine (BCM) - Baylor Heart Clinic
Houston, Texas, 77030
Indiana University
Indianapolis, Indiana, 46202
St. Vincent Medical Group, Inc.
Indianapolis, Indiana, 46260
University Of Iowa - Hospitals & Clinics
Iowa City, Iowa, 52242
Scripps Memorial Hospital
La Jolla, California, 92037
USC Keck
Los Angeles, California, 90033
Norton Pulmonary Specialists
Louisville, Kentucky, 40202
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, 53792
Medical College Of Wisconsin
Milwaukee, Wisconsin, 53226
Winthrop University Hospital
Mineola, New York, 11501
Louisiana State University
New Orleans, Louisiana, 70112 7021
Mount Sinai
New York, New York, 10029
Columbia University
New York, New York, 10032
Advocate Christ Medical Center
Oak Lawn, Illinois, 60453
Integris Baptist Office
Oklahoma City, Oklahoma, 73112
University of Nebraska Medical Center
Omaha, Nebraska, 68198-2265
University of Pennsylvania
Philadelphia, Pennsylvania, 19104-5545
Mayo Clinic
Phoenix, Arizona, 85054
Allegheny General Hospital of Research
Pittsburgh, Pennsylvania, 15212
Baylor Scott White - Plano
Plano, Texas, 75093
The Oregon Clinic
Portland, Oregon, 97220-9442
Oregon Health And Science University
Portland, Oregon, 97239-3011
Reno Heart Institute
Reno, Nevada, 89511
San Antonio Methodist TX Transplant Physicians Group
San Antonio, Texas, 78229-3771
Jeffrey S. Sager, MD Medical Corporation
Santa Barbara, California, 93105
Arizona Pulmonary Specialists, Ltd
Scottsdale, Arizona, 85258
Washington University School Of Medicine
St Louis, Missouri, 63110-1032
Saint Louis University Academic Pavillion
St Louis, Missouri, 63110
Stony Brook University Medical Center
Stony Brook, New York, 11794
Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
Torrance, California, 90502-2006
Troy Beaumont
Troy, Michigan, 53215
Cleveland Clinic
Weston, Florida, 33331 3609
Lankenau Medical Center
Wynnewood, Pennsylvania, 19096
Japan23 sites
The University of Tokyo Hospital
Bunkyō City, 113-8655
Kyushu University Hospital
Fukuoka, 812 8582
Kure Kyosai Hospital
Hiroshima, 737-8505
Kagoshima University Hospital
Kagoshima, 890 8520
St Marianna University Hospital
Kanagawa, 216 8511
Kanazawa University Hospital
Kanazawa, 920 8641
Kobe University Hospital
Kobe, 650 0017
Kurume University Hospital
Kurume, 830-0011
University Hospital Kyoto Prefectural University of Medicine
Kyoto, 602-8566
Kyoto University Hospital
Kyoto, 606 8507
Shinshu University Hospital
Matsumoto, 390 8621
Nagasaki University Hospital
Nagasaki, 852-8501
Nagoya University Hospital
Nagoya, 466 8560
Nagoya City University Hospital
Nagoya, 467 8602
Niigata University Medical And Dental Hospital
Niigata, 951 8520
Okayama University Hospital
Okayama, 700 8558
National Hospital Organization Okayama Medical Center
Okayama, 701-1192
Sapporo Medical University Hospital
Sapporo, 060 8543
Hokkaido University Hospital
Sapporo, 060-8648
National Cerebral and Cardiovascular Center
Suita-Shi, 564-8565
Juntendo University Hospital
Tokyo, 113-8431
Fujita Health University Hospital
Toyoake, 470-1192
University of Tsukuba Hospital
Tsukuba, 305 8576
Turkey (Türkiye)16 sites
Adana City Hospital
Adana, 01170
Cukurova University Medical Faculty
Adana, 01790
Ankara Etlik Speciality Hospital
Ankara, 06170
Hacettepe University Medical Faculty
Ankara, 06230
Gazi University Medical Faculty
Ankara, 06500
Ankara Bilkent Sehir Hastanesi
Ankara, 06800
Akdeniz University Medical Faculty
Antalya, 07059
Bursa Yuksek Ihtisas Training and Research Hospital
Bursa, 16310
Pamukkale Universitesi Tip Fakultesi Hastanesi
Denizli, 20160
Siyami Ersek Training and Research Hospital
Istanbul, 34668
Marmara University Medical Faculty
Istanbul, 34899
SBU Izmir Tepecik Egitim Ve Arastirma Hastanesi
Izmir, 35020
Ege Universitesi Tip Fakultesi Hastanesi
Izmir, 35100
Dokuz Eylul Universitesi Tip Fakültesi Hastanesi
Izmir, 35330
Kartal Kosuyolu Yuksek Ihtisas Egitim Ve Arastirma Hastanesi
Kartal Istanbul, 34865
Mersin University Medical Faculty
Mersin, 33110
China14 sites
Beijing Chaoyang Hospital
Beijing, 100020
Beijing Anzhen Hospital
Beijing, 100029
Peking Union Medical College Hospital
Beijing, 100730
The Second Xiangya Hospital of Central South Hospital
Changsha, 410011
West China Hospital Sichuan University
Chengdu, 610041
The First Affiliated Hospital of Chongqing Medical University
Chongqing, 400016
The First Affiliated Hospital of Guangzhou Medical University
Guangzhou, 510120
Shanghai Pulmonary Hospital
Shanghai, 200433
Renji Hospital
Shanghai, 201112
Zhongshan Hospital Fudan University
Shanghai
The General Hospital of Northern Theater Command
Shenyang, 110000
Shengjing Hospital Of China Medical University
Shenyang, 110004
Tianjin Medical University General Hospital
Tianjin, 300052
The First Affiliated Hospital of Xian Jiaotong University
Xi'an, 710061
Brazil13 sites
Universidade Federal De Minas Gerais - Hospital das Clínicas
Belo Horizonte, 30130-100
Instituto das Pequenas Missionárias de Maria Imaculada - Hospital Madre Teresa
Belo Horizonte, 30441-070
Empresa Brasileira de Servicos Hospitalares-EBSERH-Hospital Universitario de Brasilia
Brasília, 70840-901
Sociedade Hospitalar Angelina Caron - Hospital Angelina Caron
Campina Grande do Sul, 83430-000
Ceti - Centro de Estudos Em Terapias Inovadoras
Curitiba, 80060-240
Grupo ELORA Centro de Pesquisa e Ensino em Saude de Santa Catarina
Florianópolis, 88020 210
Hospital das Clinicas - UFG
Goiânia, 74605 020
Hospital De Clinicas De Porto Alegre
Porto Alegre, 90035 903
Uniao Brasileira de Educacao e Assistencia Hospital Sao Lucas da PUCRS
Porto Alegre, 90610-000
Instituto de Medicina Integral Professor Fernando Figueira
Recife, 50070-902
Instituto Dante Pazzanese de Cardiologia
São Paulo, 04012-909
Hospital Das Clinicas Da Faculdade De Medicina Da USP
São Paulo, 05403-000
Cepes - Fmabc
São Paulo, 09060-870
India13 sites
NHL Medical College (SVP Hospital IMSR)
Ahmedabad, 380006
Cims Hospital
Ahmedabad, 381060
Narayana Hrudayalaya Limited
Bangalore, 560099
SRM Medical College Hospital & Research Centre
Chengalpetu, 603203
Govindaswamy Kuppuswamy Naidu Memorial Hospital
Coimbatore, 64103
HealthWorld Hospitals
Durgapur, 713216
Renova Century Hospitals
Hyderabad, 500034
Care Hospitals
Hyderbad, 500034
Rabindranath Tagore International Institute of Cardiac Sciences
Kolkata, 700099
GB Pant Institute of Post Graduate Medical Education & Research
New Delhi, 110002
Sir Ganga Ram Hospital
New Delhi, 110060
Jawaharlal Institute of Postgraduate Medical Education and Research
Puducherry, 605008
B.D. Mehta Mahavir Heart Institute
Surat, 395001
Russia10 sites
Altay Regional Cardiological Dispensary
Barnaul, 656055
Chelyabinsk Regional Clinical Hospital
Chelyabinsk, 454076
State Autonomous HealthCare Institution 'Interregional Clinical Diagnostic Center'
Kazan', 420101
Scientific and Research Institution of Cardiovascular Diseases Complex Problems
Kemerovo, 650002
Moscow City Clinical Hospital No.51
Moscow, 121309
National Medical Research Center of Cardiology of MoH of Russian Federation
Moscow, 121552
National medical Research Center n.a. V.A.Almazov of MoH of Russian Federation
Saint Petersburg, 197341
Samara Regional Clinical Cardiological Dispensary
Samara, 443070
State Autonomous Healthcare Institution of Tyumen Region 'Scientific and Practical Medical Center'
Tyumen, 625032
Volgograd Regional Clinical Cardiology Center
Volgograd, 400008
Argentina8 sites
Sanatorio de la Trinidad Mitre
Buenos Aires, C1039AAO
Sanatorio Guemes
C.a.b.a., C1180AAX
Hospital Italiano de Buenos Aires
Caba, 1199ABB
Sanatorio Ramon Cereijo
Caba, C1048AAN
Centro Médico Dra. De Salvo
Caba, C1426ABP
Instituto de Cardiologia de Corrientes
Corrientes, W3400AMZ
Instituto Medico de La Fundacion Estudios Clinicos
Rosario, 2000
Instituto Cardiovascular de Rosario
Rosario, S2000DSR
France8 sites
CHU de Brest - Hopital de la Cavale Blanche
Brest, 29200
Hôpital Côte de Nacre
Caen
Hopital Bicetre Aphp Hopitaux Universitaires Paris Sud
Le Kremlin-Bicêtre, 94270
CHRU de Lille Hopital Claude Huriez
Lille
Aphm - Hopital Nord
Marseille, 13915
Centre Hospitalier Universitaire - de Nice - Hopital Pasteur
Nice, 06002
CHU Saint Etienne Hopital Nord
Saint-Priest-en-Jarez, 42277
Hopital Larrey CHU de Toulouse
Toulouse
Poland8 sites
Uniwersytecki Szpital Kliniczny w Bialymstoku
Bialystok, 15 276
Szpital Uniwersytecki nr 2 im dr Jana Biziela w Bydgoszczy, Klinika Kardiologii
Bydgoszcz, 85-168
Uniwersyteckie Centrum Kliniczne
Gdansk, 80214
SPSK nr 7 SUM w Katowicach Gornoslaskie Centrum Medyczne im Prof Leszka Gieca
Katowice, 40 635
Krakowski Szpital Specjalityczny im Jana Pawla II Oddzial Kliniczny Chorob Serca i Naczyn
Krakow, 31 202
Uniwersytecki Szpital Kliniczny nr 2 PUM w Szczecinie
Szczecin, 70 111
Panstwowy Instytut Medyczny Ministerstwa Spraw Wewnetrznych i Administracji
Warsaw, 02 507
Wojewodzki Szpital Specjalistyczny we Wroclawiu Osrodek Badawczo Rozwojowy
Wroclaw, 51 124
Ukraine8 sites
CNE 'Cherkasy Regional Cardiological Center of Cherkasy Regional Council'
Cherkassy, 18000
Communal Noncommercial Enterprise Cherkasy Regional Hospital of Cherkasy Regional Council
Cherkasy, 18009
MI 'Dnipropetrovsk Regional Clinical Center of Cardiology and Cardiac Surgery'
Dnipro, 49070
CNE' City Clinical Hospital #8' of Kharkiv City Council
Kharkiv, 61176
SI National Scientific Center Institute of Cardiology of M.D. Strazhesko of NAMS of Ukraine
Kyiv, 02000
State Institute Of Phthisiology And Pulmonology N.A. F.G. Yanovskiy Of Ams Ukraine
Kyiv, 03680
Communal Noncommercial Enterprise of Lviv Regional Council 'Lviv Regional Clinical Hospital'
Lviv, 79010
Municipal Non-commercial Enterprise Ternopil University Hospital of Ternopil Regional Council
Ternopil, 46002
Australia7 sites
Flinders Medical Centre
Bedford Park, 5042
Royal Prince Alfred Hospital
Camperdown, 2050
The Prince Charles Hospital
Chermside, 4032
St Vincent's hospital
Darlinghurst, 2010
Royal Hobart Hospital
Hobart, 7000
Fiona Stanley Hospital
Murdoch, 6150
Westmead Hospital
Westmead, 2145
Spain7 sites
Hosp Univ Vall D Hebron
Barcelona, 08035
Hosp. Del Mar
Barcelona, 8003
Hosp. Univ. 12 de Octubre
Madrid, 28041
Hosp. Univ. La Paz
Madrid, 28046
Hosp. Univ. Pta. de Hierro Majadahonda
Madrid, 28222
Hosp. Costa Del Sol
Málaga, 29603
Hosp Clinico Univ de Salamanca
Salamanca, 37007
Italy6 sites
ASST Grande Ospedale Metropolitano Niguarda
Milan, 20162
AOU Di Modena Policlinico Di Modena
Modena, 41125
Ospedale San Francesco
Nuoro, 08100
Fondazione IRCCS Policlinico San Matteo
Pavia, 27100
Fondazione Toscana Gabriele Monasterio CNR
Pisa, 56124
Policlinico Gemelli Universita Cattolica
Roma, 00168
Mexico6 sites
Consultorio Privado del Dr. Gabriel Arturo Ramos Lopez
Guadalajara, 44657
Operadora de Hospitales Angeles SA de CV Hospital Angeles Lomas
México, 52787
Instituto Nacional de Cardiologia Dr. Ignacio Chavez
Mexico City, 14080
Hospital Universitario Dr Jose Eleuterio Gonzalez
Monterrey, 64460
Unidad de Investigacion Clinica en Medicina S.C. (UDICEM)
Monterrey, 64718
Centro de Investigacion Clinica Chapultepec
Morelia, 58260
Thailand6 sites
Phramongkutklao Hospital and Medical College
Bangkok, 10400
Ramathibodi Hospital Mahidol University
Bangkok, 10400
Siriraj Hospital Mahidol University
Bangkok, 10700
Maharaj Nakorn Chiang Mai hospital Faculty of Medicine
Chiang Mai, 50020
Srinagarind Hospital, Khon Kaen University
Khon Kaen, 40002
Songklanagarind hospital
Songkhla, 90110
Colombia5 sites
Fundacion Neumologica Colombiana
Bogotá, 1101131
Fundacion Cardiovascular de Colombia
Bucaramanga - Piedecuesta - Valle de Menzuli, 6810002
Clínica Imbanaco S.A.S.
Cali, 760042
Centro Cardiovascular Colombiano Clínica Santa María
Medellín, 681004
Hospital Universidad del Norte
Soledad, 0000000
Israel5 sites
Carmel Medical Center
Haifa, 34362
Shaare Zedek Medical Center
Jerusalem, 91031
Kaplan Medical Center
Rehovot, 76100
The Chaim Sheba Medical Center
Tel Litwinsky, 5265601
Yitzhak Shamir Medical Center
Ẕerifin, 70300
Vietnam5 sites
Hanoi Medical University Hospital
Hanoi
Cho Ray Hospital
Ho Chi Minh City, 700000
Tam Anh Hospital
Ho Chi Minh City, 700000
Tam Duc Heart Hospital
Ho Chi Minh City, 700000
University Medical Center Ho Chi Minh city
Ho Chi Minh City, 700000
Canada4 sites
St. Joseph's Health Centre
Hamilton, Ontario, L8N 4A6
Jewish General Hospital
Montreal, Quebec, H3T 1E2
University of Ottawa Heart Institute
Ottawa, Ontario, K1Y 4W7
University Health Network - Toronto General Hospital
Toronto, Ontario, M5G2C4
Germany4 sites
Ruhr Universitat Bochum Diabeteszentrum
Bad Oeynhausen, 32545
Medizinische Hochschule Hannover
Hanover, 30625
Medizinische Klinik und Poliklinik V Klinikum Grosshadern der LMU
München, 81377
Universitaetsklinikum Regensburg
Regensburg, 93053
Greece4 sites
University Hospital of Alexandroupolis
Alexandroupoli, 681 00
Alexandra General Hospital of Athens
Athens, 11528
University Hospital Of Larissa
Larissa, 41334
Ahepa University General Hospital of Thessaloniki
Thessaloniki, 54636
Hungary4 sites
Semmelweis Egyetem,Pulmonológiai Klinika
Budapest, 1083
Gottsegen Gyorgy Orszagos Kardiovaszkularis Intezet Felnott kardiologiai osztaly
Budapest, 1096
Pecsi Tudomanyegyetem Altalanos Orvostudomanyi Kar
Pécs, 7624
Szegedi Tudományegyetem, Általános Orvostudományi Kar, Családorvosi Intézet és rendelő
Szeged, 6720
Malaysia4 sites
Hospital Pulau Pinang
George Town, 10990
Hospital Serdang
Kajang, 43000
Sarawak Heart Center
Kota Samarahan, 94300
Institut Jantung Negara (National Heart Institute)
Kuala Lumpur, 50400
Netherlands4 sites
VUMC Amsterdam
Amsterdam, 1081 HV
St. Antonius Ziekenhuis Nieuwegein
Nieuwegein, 3435 CM
Radboud Umcn
Nijmegen, 6525 GA
Erasmus MC
Rotterdam, 3015 CN
South Korea4 sites
Severance Hospital Yonsei University Health System
Seoul, 03722
Asan Medical Center
Seoul, 05505
Samsung Medical Center
Seoul, 06351
Seoul National University Hospital
Seoul, 3080
Taiwan4 sites
National Cheng Kung University Hospital
Tainan, 704
National Taiwan University Hospital
Taipei, 10002
Mackay Memorial Hospital
Taipei, 10449
Taipei Veterans General Hospital
Taipei, 112
Austria3 sites
LKH-Univ. Klinikum Graz
Graz, 8036
Ordensklinikum Linz GmbH Elisabethinen
Linz, 4020
Medical University Vienna
Vienna, 1090
Portugal3 sites
Uls Coimbra - Hosp. Univ. Coimbra
Coimbra, 3004 561
Uls Sao Jose - Hosp. Santa Marta
Lisbon, 1169-024
Uls Santa Maria - Hosp. Pulido Valente
Lisbon, 1769-001
United Kingdom3 sites
Royal Free Hospital
London, NW3 2QG
Freeman Hospital
Newcastle upon Tyne, NE7 7DN
Sheffield Teaching Hospitals NHS Foundation Trust Royal Hallamshire Hospital
Sheffield, S10 2RX
Belarus2 sites
The Republican Scientific-Practical Center ''Cardiology''
Minsk, 220036
Minsk Regional Clinical Hospital
Minsk, 220143
Bulgaria2 sites
Multiprofile Hospital For Active Treatment National Cardiology Hospital, Ead
Sofia, 1309
University Multiprofile Hospital for Active Treatment- UMHAT Sveta Anna AD
Sofia, 1750
Norway2 sites
Akershus Universitetssykehus
Nordbyhagen, 1478
Oslo University Hospital
Oslo, 372
Saudi Arabia2 sites
King Faisal Specialist Hospital & Research Center
Riyadh, 11564
King Fahad Medical City
Riyadh, 59046
Serbia2 sites
University Clinical Center of Serbia
Belgrade, 11000
Institute for Pulmonary Disease of Vojvodina
Kamenitz, 21204
Singapore2 sites
National University Heart Centre, Singapore
Singapore, 119228
National Heart Centre (NHC) Singapore
Singapore, 169609
Slovakia2 sites
Narodny ustav srdcovych a cievnych chorob
Bratislava, 833 48
The Eastern Slovakia Institute of Cardiovascular Diseases
Košice, 040 11
Sweden2 sites
Sahlgrenska Universitetsjukhuset
Gothenburg, 413 45
Skanes universitetssjukhus
Lund, 221 85
Czechia1 site
General University Hospital II.department of Internal Medicine-cardiology and angiology
Prague, 128 08
Denmark1 site
Århus Universitetshospital, Skejby, Hjertemedicinsk Afdeling B
Aarhus, 8200
About this study
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
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.
- Conditions
- Pulmonary Arterial Hypertension
- Being tested
- Macitentan 10 mg, Macitentan 37.5 mg, Macitentan 75 mg, Placebo
- Medical subject headings
- Pulmonary Arterial Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Macitentan 10 mgDrug
Also called JNJ-67896062
Participants will receive macitentan 10 mg film-coated tablets orally.
Macitentan 37.5 mgDrug
Also called JNJ-67896062
Participants will receive macitentan 37.5 mg film-coated tablets orally.
Macitentan 75 mgDrug
Also called JNJ-67896062
Participants will receive macitentan 75 mg film-coated tablets orally.
PlaceboDrug
Participants will receive matching placebo film-coated tablets orally.
| Study group | Role | What they receive |
|---|---|---|
| Macitentan 10 milligrams (mg) + Placebo | Active comparator | 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. Receives: Drug: Macitentan 10 mg; Drug: Macitentan 37.5 mg; Drug: Macitentan 75 mg; Drug: Placebo |
| Macitentan 75 mg + Placebo | Experimental | 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. Receives: Drug: Macitentan 10 mg; Drug: Macitentan 37.5 mg; Drug: Macitentan 75 mg; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to 4 years
Secondary outcomes (6)
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.
Measured: Baseline up to Week 24
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.
Measured: Up to 4 years
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.
Measured: Baseline up to Week 24
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.
Measured: Baseline up to Week 24
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.
Measured: Up to 4 years
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.
Measured: Up to 6 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Feb 2020
- Study start30 Jun 2020
- Primary completion7 Oct 2025
- Study completion20 Feb 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Pulmonary Arterial HypertensionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 935 participants (actual)
Sponsor and investigators
- Lead sponsor
- Actelion
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Actelion Clinical Trials, Study director, Actelion
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04273945
- Sponsor's protocol ID
- CR108740
- Other IDs
- AC-055-315, 2019-002533-11, 2024-515669-32-00, 2019
- Acronym
- UNISUS
- Status last verified
- Oct 2026
- First submitted
- 31 Jan 2020
- Last updated
- 6 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: The data sharing policy of the Janssen Pharmaceutical Companies of Johnson \& Johnson is available at www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu.
Publications
Csonka D, Gargano C, Goyal N, De Meulder M, Yartsev V, Ruixo JJP. Effect of Once-Daily Macitentan 75 mg on the Pharmacokinetics of Sildenafil, Riociguat, or Rosuvastatin in Healthy Male Participants. J Clin Pharmacol. 2026 Apr;66(4):e70185. doi: 10.1002/jcph.70185.
PubMed 42023995