AzTrials
AzTrials

Chronic Thromboembolic Pulmonary HypertensionPhase 3MACiTEPHNCT04271475

A Study to Evaluate Efficacy and Safety of Macitentan 75 mg in Inoperable or Persistent/Recurrent Chronic Thromboembolic Pulmonary Hypertension

A Phase 3 study testing Macitentan in people with Chronic Thromboembolic Pulmonary Hypertension, run by Actelion at 168 sites in 33 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

The purpose of the study is to evaluate the effect of macitentan 75 mg versus placebo on exercise capacity at Week 28 in participants with chronic thromboembolic pulmonary hypertension (CTEPH). Read more about this study

Who is it for?
Ages 18 to 80 years
What is being tested?
Macitentan
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
127 participants
Where
168 sitesin 33 countries
Study dates
7 Jul 2020to 21 Dec 2023
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Chronic thromboembolic pulmonary hypertension (CTEPH) (World Health Organization [WHO] Group 4) fulfilling one of the following criteria: a) inoperable due to the localization of the obstruction being surgically inaccessible (that is, distal disease), b) persistent/recurrent CTEPH after balloon pulmonary angioplasty (BPA), and deemed inoperable due to the localization of the obstruction being surgically inaccessible (that is, distal disease), c) persistent/recurrent CTEPH after rescue pulmonary endarterectomy (PEA)
  • 6-minute walk distance (6MWD) greater than or equal to (>=) 100 meter (m) and less than or equal to (<=) 450 meters (m), documented by an eligibility and a baseline 6-minute walk test (6MWT). The baseline 6MWD must not differ by more than 15 percent (%) from the eligibility test
  • World Health Organization functional class (WHO FC) >= II
  • Participants are to receive riociguat as per local standard of care, unless it is contraindicated or unavailable

Who cannot join

  • Acute pulmonary embolism within 3 months prior to or during Screening
  • Planned balloon pulmonary angioplasty (BPA) during the fixed duration part of the double-blind period
  • Significant obstructive and restrictive lung disease
  • Acute or chronic conditions (other than dyspnea) that limit the ability to comply with study requirements, in particular with 6MWT (for example, intermittent claudication).
  • Symptomatic coronary artery disease requiring an intervention within 3 months prior to or during Screening or anticipated during the fixed duration part of the study
  • Decompensated cardiac failure if not under close supervision
Show all 17Show fewer
  • Known and documented life-threatening cardiac arrhythmias
  • Acute myocardial infarction within 6 months prior to, or during Screening
  • Cerebrovascular events (including transient ischemic attack) within 3 months prior to, or during Screening
  • Known or suspicion of pulmonary veno-occlusive disease (PVOD)
  • Administration of ERAs, intravenous prostacyclins / prostacyclin analogs, or investigational treatment within 90 days prior to Randomization
  • Change in dose or initiation of Phosphodiesterase type-5 (PDE-5) inhibitors, oral, inhaled or subcutaneous (SC) prostacyclins / prostacyclin analogues, prostacyclin receptor agonists or riociguat, a) within 90 days prior to Randomization, or b) anticipated during the fixed duration part of the double-blind [DB] period
  • Hypotension, that is, systolic blood pressure (SBP) less than (<) 90 millimeters of mercury (mmHg) or diastolic blood pressure (DBP) <50 mmHg at Screening.
  • Severe renal dysfunction with an estimated Glomerular Filtration Rate <30 milliliters per minute per 1.73 meter square (mL/min/1.73 m^2) using the Chronic Kidney Disease Epidemiology Collaboration formula at 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) greater than or equal to (>=) 1.5*upper limit of normal (ULN) at Screening
  • Hemoglobin <100 g/L (<10 gram per deciliter [g/dL]) at Screening

Trial locations and contacts

168 sites in 33 countries.

168 sites in 33 countries

United States24 sites

  • University of New Mexico School of Medicine

    Albuquerque, New Mexico, 87131

  • Piedmont Healthcare

    Atlanta, Georgia, 30309

  • University of Colorado Anschutz Medical Campus

    Aurora, Colorado, 80045

  • University of Maryland

    Baltimore, Maryland, 21201

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • Tufts Medical Center

    Boston, Massachusetts, 21118

  • Northwestern University Feinberg School of Medicine

    Chicago, Illinois, 60611

  • Cleveland Clinic

    Cleveland, Ohio, 44195

  • University of Florida Health Jacksonville

    Gainesville, Florida, 32608

  • Indiana University

    Indianapolis, Indiana, 46202

  • University of Kansas Medical Center

    Kansas City, Kansas, 66160

  • University of California San Diego Medical Center

    La Jolla, California, 92037

  • Keck School of Medicine of USC

    Los Angeles, California, 90033

  • University of Wisconsin Hospital and Clinics

    Madison, Wisconsin, 53792-2442

  • Intermountain Medical Center

    Murray, Utah, 84107

  • Yale University School Of Medicine

    New Haven, Connecticut, 06519

  • University of Nebraska Medical Center

    Omaha, Nebraska, 68198-2265

  • University of Pittsburgh Medical Center

    Pittsburgh, Pennsylvania, 15213

  • Baylor Scott White - Plano

    Plano, Texas, 75093

  • Legacy Hospital

    Portland, Oregon, 97210

  • VA Sierra Nevada Health Care System

    Reno, Nevada, 89509

  • UC Davis Medical Center

    Sacramento, California, 95817-2201

  • University of Utah Cardiovascular Center

    Salt Lake City, Utah, 84132

  • Syracuse VA Medical Center

    Syracuse, New York, 13210

Other trials in United States

Japan16 sites

  • The University of Tokyo Hospital

    Bunkyō City, 113-8655

  • Kyushu University Hospital

    Fukuoka, 812 8582

  • Kure Kyosai Hospital

    Hiroshima, 737-8505

  • St Marianna University Hospital

    Kanagawa, 216 8511

  • Kobe University Hospital

    Kobe, 650 0017

  • University Hospital Kyoto Prefectural University of Medicine

    Kyoto, 602-8566

  • Kyoto University Hospital

    Kyoto, 606 8507

  • Shinshu University Hospital

    Matsumoto, 390 8621

  • Toho University Medical Center, Ohashi Hospital

    Meguro-ku, 153-8515

  • Kyorin University Hospital

    Mitaka, 181-8611

  • Nagoya University Hospital

    Nagoya, 466 8560

  • National Hospital Organization Okayama Medical Center

    Okayama, 701-1192

  • Hokkaido University Hospital

    Sapporo, 060-8648

  • National Cerebral and Cardiovascular Center

    Suita-Shi, 564-8565

  • Juntendo University Hospital

    Tokyo, 113-8431

  • University of Tsukuba Hospital

    Tsukuba, 305 8576

Other trials in Japan

China15 sites

  • Beijing Chaoyang Hospital

    Beijing, 100020

  • Beijing Anzhen Hospital

    Beijing, 100029

  • China Japan Friendship Hospital

    Beijing, 100029

  • Beijing Shijitan Hospital

    Beijing, 100038

  • The First Affiliated Hospital of Chongqing Medical University

    Chongqing, 400016

  • The First Affiliated Hospital of Guangzhou Medical University

    Guangzhou, 510140

  • Sir Run Run Shaw Hospital Zhejiang University School of Medicine

    Hangzhou, 310016

  • Zhongda Hospital Southeast University

    Nanjing, 210009

  • The Affiliated Hospital of Medical College Qingdao University

    Qingdao, 266003

  • Huashan Hospital of Fudan University

    Shanghai, 200040

  • Shanghai Pulmonary Hospital

    Shanghai, 200433

  • Zhongshan Hospital Fudan University

    Shanghai

  • The General Hospital of Northern Theater Command

    Shenyang, 110000

  • Tianjin Medical University General Hospital

    Tianjin, 300052

  • The First Affiliated Hospital of Xian Jiaotong University

    Xi'an, 710061

Other trials in China

Turkey (Türkiye)13 sites

  • Adana City Hospital

    Adana, 01170

  • Cukurova University Medical Faculty

    Adana, 01250

  • Hacettepe University Medical Faculty

    Ankara, 06230

  • Ankara Bilkent Sehir Hastanesi

    Ankara, 06800

  • Pamukkale University Medical Faculty

    Denizli, 20070

  • Eskisehir Osmangazi University Medical Faculty Hospital

    Eskişehir, 26040

  • Istanbul University - Cerrahpasa Cardiology Institution

    Istanbul, 34096

  • Siyami Ersek Training and Research Hospital

    Istanbul, 34668

  • Marmara University Medical Faculty

    Istanbul, 34899

  • Ege University Medical Faculty

    Izmir, 35100

  • Dokuz Eylul University Medical Faculty

    Izmir, 35340

  • Kartal Kosuyolu Yuksek Ihtisas Egitim Ve Arastirma Hastanesi

    Kartal Istanbul, 34865

  • Mersin University Medical Faculty

    Mersin, 33110

Other trials in Turkey (Türkiye)

Germany9 sites

  • Universitatsklinikum Bonn

    Bonn, 53127

  • Medizinische Fakultaet Carl Gustav Carus Technische Universitaet Dresden

    Dresden, 01307

  • Universitaetsklinikum Giessen

    Giessen, 35392

  • Universitaetsklinikum Hamburg Eppendorf

    Hamburg, 20246

  • Medizinische Hochschule Hannover Zentrum Innere Medizin Klinik für Pneumologie

    Hanover, 30625

  • Thoraxklinik Heidelberg

    Heidelberg, 69126

  • Universitaetsklinikum des Saarlandes

    Homburg, 66421

  • Universitatsklinikum Jena

    Jena, 07747

  • Krankenhaus Neuwittelsbach

    München, 80639

Other trials in Germany

France8 sites

  • CHU de Brest - Hopital de la Cavale Blanche

    Brest, 29200

  • CHU de Grenoble Hopital Albert Michallon

    Grenoble, 38043

  • Hopital Bicetre Aphp Hopitaux Universitaires Paris Sud

    Le Kremlin-Bicêtre, 94275

  • Hôpital Cardiologique - Chru Lille

    Lille, 59037

  • CHU de Montpellier - Arnaud de Villeneuve

    Montpellier, 34295

  • CHU Saint Etienne Hopital Nord

    Saint-Priest-en-Jarez, 42277

  • Hopital Larrey CHU de Toulouse

    Toulouse

  • CHU de Nancy - Hopital de Brabois

    Vandœuvre-lès-Nancy, 54511

Other trials in France

Spain6 sites

  • Hosp Clinic de Barcelona

    Barcelona, 08036

  • Hosp. Univ. 12 de Octubre

    Madrid, 28041

  • Hosp. Univ. La Paz

    Madrid, 28046

  • Hosp Virgen de La Victoria

    Málaga, 29010

  • Hosp. Costa Del Sol

    Málaga, 29603

  • Hosp. Gral. Univ. de Toledo

    Toledo, 45007

Other trials in Spain

Ukraine6 sites

  • CNE 'Cherkasy Regional Cardiological Center of Cherkasy Regional Council'

    Cherkasy, 18009

  • CE 'Dnipropetrovsk Regional Clinical Center of Cardiology and Cardiosurgery'

    Dnipro, 49059

  • 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

Other trials in Ukraine

United Kingdom6 sites

  • Papworth Hospital NHS Trust

    Cambridge, CB2 0AY

  • National Waiting Times Centre Board Golden Jubilee National Hospital

    Glasgow, G81 4DY

  • Royal Free Hospital

    London, NW3 2QG

  • Hammersmith Hospital

    London, W12 0HS

  • Freeman Hospital

    Newcastle upon Tyne, NE7 7DN

  • Sheffield Teaching Hospitals NHS Foundation Trust Royal Hallamshire Hospital

    Sheffield, S10 2RX

Other trials in United Kingdom

Italy5 sites

  • Ospedale SS. Annunziata

    Chieti, 66100

  • Fondazione IRCCS Policlinico San Matteo

    Pavia, 27100

  • Fondazione Toscana Gabriele Monasterio CNR

    Pisa, 56124

  • Policlinico Gemelli Universita Cattolica

    Roma, 00168

  • A.O.U. Città della Salute e della Scienza

    Torino, 10126

Other trials in Italy

Mexico5 sites

  • Operadora de Hospitales Angeles SA de CV Hospital Angeles Lomas

    México, 52787

  • Instituto Nacional de Cardiologia Dr. Ignacio Chavez

    Mexico City, 14080

  • Unidad de Investigacion Clinica en Medicina S.C. (UDICEM)

    Monterrey, 64718

  • Centro de Investigacion Clinica Chapultepec

    Morelia, 58260

  • CRI Centro Regiomontano de Investigacion SC

    Nuevo León, 64060

Other trials in Mexico

Russia5 sites

  • State Autonomous HealthCare Institution 'Interregional Clinical Diagnostic Center'

    Kazan', 420101

  • 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

  • Volgograd Regional Clinical Cardiology Center

    Volgograd, 400008

Other trials in Russia

South Korea5 sites

  • Pusan National University Hospital

    Busan, 49241

  • Seoul National University Hospital

    Seoul, 03080

  • Asan Medical Center

    Seoul, 05505

  • Samsung Medical Center

    Seoul, 06351

  • The Catholic University of Korea Seoul St Marys Hospital

    Seoul, 06591

Other trials in South Korea

Colombia4 sites

  • Fundacion Neumologica Colombiana

    Bogotá, 1101131

  • Fundación Abood Shaio

    Bogotá, 85369

  • Clínica Imbanaco S.A.S.

    Cali, 760042

  • Centro Cardiovascular Colombiano Clínica Santa María

    Medellín, 681004

Other trials in Colombia

Taiwan4 sites

  • Kaohsiung Veterans General Hospital

    Kaohsiung City, 813

  • National Taiwan University Hospital

    Taipei, 10002

  • Taipei Veterans General Hospital

    Taipei, 112

  • Chang-Gung Memorial Hospital, LinKou Branch

    Taoyuan, 333

Other trials in Taiwan

Argentina3 sites

  • Nexo Salud Investigacion Clinica

    Buenos Aires, C1006ACC

  • Sanatorio de la Trinidad Mitre

    Buenos Aires, C1039AAO

  • Sanatorio Guemes

    C.a.b.a., C1180AAX

Other trials in Argentina

Austria3 sites

  • LKH-Univ. Klinikum Graz

    Graz, 8036

  • Ordensklinikum Linz GmbH Elisabethinen

    Linz, 4020

  • Medizinische Universitaet Wien

    Vienna, 1090

Other trials in Austria

Canada3 sites

  • University Of Calgary - Peter Lougheed Centre

    Calgary, Alberta, T1Y 6J4

  • University of Alberta Hospital

    Edmonton, Alberta, T6G 2B7

  • University Health Network - Toronto General Hospital

    Toronto, Ontario, M5G 2N2

Other trials in Canada

Poland3 sites

  • Krakowski Szpital Specjalistyczny im Jana Pawla II

    Krakow, 31 202

  • Wojewodzki Szpital Specjalistyczny im Stefana Kardynala Wyszynskiego PZOZ

    Lublin, 20 708

  • Europejskie Centrum Zdrowia Otwock Sp z o o

    Otwock, 05 400

Other trials in Poland

Thailand3 sites

  • Maharaj Nakorn Chiang Mai Hospital

    Chiang Mai, 50200

  • Srinagarind Hospital, Khon Kaen University

    Khon Kaen, 40002

  • Thammasat Hospital

    Pathum Thani, 12120

Other trials in Thailand

Australia2 sites

  • Queensland Lung Transplant Service

    Chermside, 4032

  • St Vincent's hospital

    Darlinghurst, 2010

Other trials in Australia

Bulgaria2 sites

  • Military Medical Academy

    Sofia, 1606

  • University Multiprofile Hospital for Active Treatment- UMHAT Sveta Anna AD

    Sofia, 1750

Other trials in Bulgaria

Hungary2 sites

  • Gottsegen Gyorgy Orszagos Kardiovaszkularis Intezet Felnott kardiologiai osztaly

    Budapest, 1096

  • Szegedi Tudományegyetem, Általános Orvostudományi Kar, Családorvosi Intézet és rendelő

    Szeged, 6720

Other trials in Hungary

Israel2 sites

  • Tel Aviv Medical Center

    Tel Aviv, 6423906

  • The Chaim Sheba Medical Center

    Tel HaShomer, 5265601

Other trials in Israel

Lithuania2 sites

  • Lietuvos sveikatos mokslų universiteto ligoninė Kauno klinik

    Kaunas, 50161

  • Vilnius University Hospital Santariskiu Klinikos

    Vilnius, LT-08661

Other trials in Lithuania

Romania2 sites

  • Institutul de urgenta pentru Boli Cardiovasculare Prof. Dr. C.C. Iliescu

    Bucharest, 022328

  • Spitalul Clinic Judetean de Urgenta

    Tg. Mures, 540136

Other trials in Romania

Saudi Arabia2 sites

  • King Faisal Specialist Hospital & Research Center

    Riyadh, 12713

  • King Fahad Medical City

    Riyadh, 59046

Other trials in Saudi Arabia

Serbia2 sites

  • University Clinical Center of Serbia

    Belgrade, 11000

  • Institute for Pulmonary Disease of Vojvodina

    Kamenitz, 21204

Other trials in Serbia

Singapore2 sites

  • National University Heart Centre, Singapore

    Singapore, 119228

  • National Heart Centre (NHC) Singapore

    Singapore, 169609

Other trials in Singapore

Czechia1 site

  • General University Hospital II.department of Internal Medicine-cardiology and angiology

    Prague, 128 08

Other trials in Czechia

Denmark1 site

  • Århus Universitetshospital, Skejby, Hjertemedicinsk Afdeling B

    Aarhus N, 8200

Other trials in Denmark

Portugal1 site

  • Uls Almada Seixal - Hosp. Garcia de Orta

    Almada, 2805 267

Other trials in Portugal

Slovakia1 site

  • Narodny ustav srdcovych a cievnych chorob

    Bratislava, 833 48

Other trials in Slovakia

About this study

Official title: A Prospective, Randomized, Double-blind, Multicenter, Placebo-controlled, Parallel Group, Adaptive Phase 3 Study With Open-label Extension to Evaluate Efficacy and Safety of Macitentan 75 mg in Inoperable or Persistent/Recurrent Chronic Thromboembolic Pulmonary Hypertension

The purpose of the study is to evaluate the effect of macitentan 75 mg versus placebo on exercise capacity at Week 28 in participants with chronic thromboembolic pulmonary hypertension (CTEPH).

Read the detailed description

CTEPH is one of the leading causes of severe pulmonary hypertension (PH), classified within World Health Organization (WHO) group 4 PH. It is a rare, progressive pulmonary vascular disease that if left untreated, leads to progressively increasing pulmonary vascular resistance (PVR) and eventually right ventricle failure and death. Histopathologic findings including endothelial cell dysfunction and distal pulmonary arterial remodeling are shared between PAH and CTEPH, and PH-specific therapies (that is, riociguat) have shown efficacy in inoperable and persistent/recurrent CTEPH. The endothelin receptor antagonist macitentan offers a different mode of action and addresses an important unmet medical need for an alternative treatment option in this indication. This study will assess the effect of macitentan 75 mg on exercise capacity in CTEPH. The total duration of the study is approximately 6 years. The study comprises of a screening period (at least 14 days and up to 60 days), a double-blind (DB) treatment period (28 weeks [minimum duration] up to 3.5 years), an open-label (OL) extension period (starts at end-of-DB-treatment [EODBT] and will end for all participants 104 weeks after the last participant has completed DB Week 28). The DB period consists of an 8-week up-titration phase and a maintenance phase. The maintenance phase is divided into a 28-week fixed duration part, at the end of which primary endpoint is assessed, and a variable duration part. The duration of the DB period for an individual participant depends on the timepoint of entry into the study and whether a CEC-confirmed clinical worsening event occurred. Participants who discontinue DB study intervention during the 28-week fixed duration part will be followed until Week 28 in a post-treatment observation period (PTOP).

Being tested
Macitentan, Placebo

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MacitentanDrug

    Also called ACT-064992,, Opsumit

    Participants will receive Macitentan film-coated tablets orally od.

  • PlaceboDrug

    Participant will receive matching placebo tablets orally od.

Study groups in NCT04271475
Study groupRoleWhat they receive
MacitentanExperimentalParticipant will receive macitentan at a dose of 10 milligram (mg) once daily (OD) for 4 weeks, followed by a dose of macitentan 37.5 mg for another 4 weeks and continue with the target dose of macitentan 75 mg. Participants who have reached the target dose of 75 mg, completed the Double-blind (DB) period up to Week 28 (either on treatment or in Post-treatment observation period [PTOP]) at minimum, may be eligible for transitioning into the Open label (OL) extension period once all participants have completed the DB part of the study, or earlier if they experienced a Clinical event committee (CEC) confirmed clinical worsening event.
Receives: Drug: Macitentan
PlaceboExperimentalParticipants will receive placebo tablets matching the macitentan 10 mg, macitentan 37.5mg and macitentan 75 mg tablets, respectively. Participants who completed the DB period as per protocol either on treatment or in PTOP are eligible for transitioning to the OL extension period and will receive macitentan 75 mg after an 8-week double-dummy uptitration (macitentan 10 mg for 4 weeks, followed by 37.5 mg for another 4 weeks).
Receives: Drug: Macitentan; Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change From Baseline in 6-minute Walk Distance (6MWD) at Week 28

    Change from baseline in 6MWD as measured by 6-minute walk test (6MWT) at Week 28 was reported. The purpose of the 6MWT was to quantify exercise tolerance and capacity. This standardized test measured the distance an individual was able to walk over a total of six minutes on a hard, flat surface with no obstacles. The goal was for the individual to walk as far as possible in 6 minutes.

    Measured: Baseline (Day 1), Week 28

Secondary outcomes (6)

  1. Time to First Clinical Event Committee (CEC) Confirmed Clinical Worsening up to End-of Double-blind-treatment (EODBT) Period

    Time (months) to first CEC-confirmed clinical worsening up to EODBT were reported. Clinical worsening was defined as the occurrence of at least one of the following events: 1) All-cause death; 2) Heart and/or lung transplantation; 3) Unplanned pulmonary hypertension (PH)-related hospitalization; 4) PH-related deterioration from baseline identified by at least one of the following: a) Persistent increase in World Health Organization functional class (WHO FC) that could not be explained by another cause (for example, viral infection); b) Persistent deterioration by at least 15 percent (%) in exercise capacity; as measured by the 6MWD; c) New or worsened signs or symptoms of right heart failure; 5) Rescue pulmonary endarterectomy (PEA) and/or balloon pulmonary angioplasty (BPA) procedure due to worsening of PH.

    Measured: From Baseline (Day 1) up to EODBT: median 24.5 weeks (min 3.9 weeks; max 160.4 weeks) for macitentan, median 44 weeks (min 4 weeks; max 147.9 weeks) for placebo

  2. Number of Participants With Improvement in World Health Organization Functional Class (WHO FC) From Baseline to Week 28

    Number of participants with improvement in WHO FC from baseline to Week 28 were reported. Improvement (decrease) in WHO FC from baseline to Week 28 was calculated for each participant. WHO FC test was used to assess disease severity. Four functional classes (FC) were defined from FC I (no limitation of physical activity) to FC IV (inability to carry out any physical activity without symptoms). For the analysis purpose, these WHO FC class values were transformed to a scale with scores ranged from 1 to 4; where a score of 1 corresponded to WHO FC Class I and a score of 4 corresponded to WHO FC Class IV. The higher scores indicate greater symptom severity or worse impact. Improvement was considered when a participant changed from a higher class to a lower class.

    Measured: From Baseline (Day 1) up to Week 28

  3. Change From Baseline to Week 28 in Pulmonary Arterial Hypertension - Symptoms and Impact (PAH-SYMPACT) - Cardiopulmonary Symptom Domain Score

    The cardiopulmonary symptoms domain consisted of 6 items: shortness of breath, fatigue, lack of energy, swelling in ankles or legs, swelling in stomach area and cough and were reported on a 5-point Likert scale from 0 (no symptom at all) to 4 (very severe symptoms), with higher score indicating more symptom. The symptoms part of the PAH-SYMPACT was administered daily over a 7-day period. The recall period of symptom items was the last 24 hours. The mean individual symptom item score was determined for each of the 6 items and a domain score was calculated by summing the mean individual symptom item scores and dividing by the number of items, ranged from 0=no cardiopulmonary symptoms to 4=severe cardiopulmonary symptoms. A higher score indicated more severe symptoms experienced.

    Measured: From Baseline (Day 1) up to Week 28

  4. Change From Baseline to Week 28 in PAH-SYMPACT - Cardiovascular Symptom Domain Score

    The cardiovascular symptoms domain consisted of 5 items: heart palpitations (fluttering), rapid heartbeat, chest pain, chest tightness, and lightheadedness and were reported on a 5-point Likert scale ranged from 0 (no symptoms at al) to 4 (very severe symptoms), with high score indicating more symptom. The symptoms part of PAH-SYMPACT was administered daily over a 7-day period. The recall period of symptom items was the last 24 hours. An average Cardiovascular Symptoms domain score was determined based on the daily scores of the 5 items. The mean individual symptom item score was determined for each of the 5 items and a domain score was calculated by summing the mean individual symptom item scores and dividing by the number of items, ranged from 0=no cardiovascular symptoms to 4=severe cardiovascular symptoms. Higher score indicated more severe symptoms experienced.

    Measured: From Baseline (Day 1) up to Week 28

  5. Change From Baseline to Week 28 in Euro Quality of Life-5-Dimension-5-Level (EQ-5D-5L) Utility Score and Visual Analog Scale (VAS) Score

    The EQ-5D-5L was a generic measure of health status. The EQ-5D-5L consisted of 2 parts: EQ-5D-5L utility score (descriptive system) and VAS score. EQ-5D-5L descriptive system consisted of 5-item questionnaire that assessed 5 domains including mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each questionnaire had 5 response levels: 1 =no problems, 2 =slight problems, 3 =moderate problems, 4 =severe problems and 5 =extreme problems. The scores for the 5 questionnaires were used to compute a single utility score which ranged from 0 to 1, where higher score indicated better health state and lower score indicated worse health state. EQ-5D-5L VAS rated current health state on a vertical scale with a score ranged from 0 (worst imaginable health state) to 100 (best imaginable health state), higher scores indicated a better health state.

    Measured: From Baseline (Day 1) up to Week 28

  6. Change From Baseline to Week 28 in Accelerometer-assessed Proportion of Time Spent in Moderate to Vigorous Physical Activity

    Change from baseline to Week 28 in accelerometer-assessed proportion of time spent in moderate to vigorous physical activity were assessed. Daily life physical activity of participant was assessed using accelerometer which was provided to the participant at screening and was worn daily during waking hours up to Week 28. For each scheduled visit, the 14 days prior to the visit were considered as the assessment period for physical activity. To be considered evaluable for a given timepoint, actigraphy variables should have been measured for at least 7 complete days (consecutive or not). A complete day is defined as a record of at least 7 waking hours of data. Proportion of time spent in moderate to vigorous physical activity was the estimated number of minutes spent in moderate or higher physical activity as calculated using the Staudenmayer '15 technique as proportion of the total minutes of algorithmically detected wear time and excluding the minutes that fall within a sleep period.

    Measured: From Baseline (Day 1) up to Week 28

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Feb 2020
  2. Study start7 Jul 2020
  3. Primary completion21 Dec 2023
  4. Study completion21 Dec 2023

Why it stopped: The Sponsor decided to stop the study for futility based on a recommendation by the IDMC following a pre-planned interim analysis

Resources

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
Double blind
Who is masked
Participant, Investigator
Enrolment
127 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04271475
Sponsor's protocol ID
CR108742
Other IDs
67896062CTP3001, 2019-004131-24, 2019
Acronym
MACiTEPH
Status last verified
Jun 2025
First submitted
13 Feb 2020
Last updated
27 Jun 2025
Data monitoring committee
No
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

  • Inacio Cazeiro D, Azaredo Raposo M, Guimaraes T, Lousada N, Jenkins D, R Inacio J, Moreira S, Mineiro A, Freitas C, Martins S, Ferreira R, Luis R, Cardim N, Pinto FJ, Placido R. Chronic thromboembolic pulmonary hypertension: A comprehensive review of pathogenesis, diagnosis, and treatment strategies. Rev Port Cardiol. 2025 Feb;44(2):121-137. doi: 10.1016/j.repc.2024.04.006. Epub 2024 Jun 28. English, Portuguese.

    PubMed 38945473

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Macitentan in people with Chronic Thromboembolic Pulmonary Hypertension, run by Actelion at 168 sites in 33 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 27 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 168 sites in United States, Japan, China, Turkey (Türkiye), Germany and 28 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 22 Apr 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline in 6-minute Walk Distance (6MWD) at Week 28 (time frame: Baseline (Day 1), Week 28). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04271475, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jun 2025.

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