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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT04271475




Registration number
NCT04271475
Ethics application status
Date submitted
13/02/2020
Date registered
17/02/2020
Date last updated
25/11/2020

Titles & IDs
Public title
A Study to Evaluate Efficacy and Safety of Macitentan 75 mg in Inoperable or Persistent/Recurrent Chronic Thromboembolic Pulmonary Hypertension
Scientific 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
Secondary ID [1] 0 0
2019-004131-24
Secondary ID [2] 0 0
CR108742
Universal Trial Number (UTN)
Trial acronym
MACiTEPH
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Thromboembolic Pulmonary Hypertension 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Cardiovascular 0 0 0 0
Hypertension

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Macitentan
Treatment: Drugs - Placebo

Experimental: Macitentan - Participant will receive macitentan at a dose of 10 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 macitentan 75 mg and completed the double blind (DB) period as per protocol (up to Week 52; either on treatment or in post treatment observation period [PTOP]) are eligible for transitioning into the open-label (OL) extension period and will receive macitentan 75 mg.

Experimental: Placebo - Participants 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 (up to Week 52; 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 37.5mg for another 4 weeks).


Treatment: Drugs: Macitentan
Participants will receive Macitentan film-coated tablets orally od.

Treatment: Drugs: Placebo
Participant will receive matching placebo tablets orally od.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change From Baseline to Week 28 in 6- minute Walk Distance [6MWD] - Change from baseline to week 28 in 6MWD as measured by 6-minute walk test [6MWT]) will be reported. The purpose of the six-minute walk test (6MWT) is 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 6 minutes.
Timepoint [1] 0 0
Baseline up to Week 28
Secondary outcome [1] 0 0
Time to Clinical Worsening up to Week 52 - Clinical event committee (CEC) confirmed clinical worsening up to Week 52 will be reported. Clinical worsening is defined as the occurrence of at least one of the following events: All-cause death; Heart and/or lung transplantation; Unplanned pulmonary hypertension (PH)-related hospitalization; Persistent increase in World Health Organization functional class (WHO FC) that cannot be explained by another cause (for example, viral infection); Persistent deterioration by at least 15 percent (%) in exercise capacity; as measured by the 6MWD; New or worsening signs or symptoms of right heart failure; Initiation or dose escalation of PH-specific therapy due to worsening of PH based on additional assessments performed at the discretion of the investigator and confirmed by the CEC; or Rescue pulmonary endarterectomy (PEA) and/or balloon pulmonary angioplasty (BPA) procedure due to worsening of PH.
Timepoint [1] 0 0
Up to Week 52
Secondary outcome [2] 0 0
Number of Participants with Improvement in WHO Functional Class (WHO FC) From Baseline to Week 28 - Improvement in WHO FC from baseline to Week 28 will be calculated for each participant. WHO FC test is used to assess disease severity. Four functional classes (FC) are defined from FC I (no limitation of physical activity) to FC IV (inability to carry out any physical activity without symptoms). Improvement is considered when a participant changes from a higher class to a lower class.
Timepoint [2] 0 0
Baseline up to Week 28
Secondary outcome [3] 0 0
Change From Baseline to Week 28 in Pulmonary Arterial Hypertension - Symptoms Based on (PAH-SYMPACT) - Cardiopulmonary Symptom Domain Score - The Cardiopulmonary Symptoms domain consists of 6 items (shortness of breath, fatigue, lack of energy, swelling in ankles or legs, swelling in stomach area and cough) 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-SYMPACT will be administered daily over 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. It will be administered two times (daily for 7 days each time) prior to administration of Macitentan. Questionnaires to be completed at site at screening for training purpose. PAH-SYMPACT to be performed at home, during the 7-day period prior to the scheduled visit.
Timepoint [3] 0 0
Baseline up to Week 28
Secondary outcome [4] 0 0
Change from Baseline to Week 28 in PAH-SYMPACT - Cardiovascular Symptom Domain Score - The Cardiovascular Symptoms domain consists of 5 items (heart palpitations [fluttering], rapid heartbeat, chest pain, chest tightness, and lightheadedness) 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 will be administered daily over 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. It will be administered two times (daily for 7 days each time) prior to administration of Macitentan Questionnaires to be completed at site at screening for training purpose. PAH-SYMPACT to be performed at home, during the 7-day period prior to the scheduled visit.
Timepoint [4] 0 0
Baseline up to Week 28
Secondary outcome [5] 0 0
Change from baseline to Week 28 in Euro Quality of life-5-Dimension-5-Level (EQ-5D-5L) Utility Score - The EQ-5D-5L is a generic measure of health status. The EQ-5D-5L is a 5-item questionnaire that assesses 5 domains including mobility, self-care, usual activities, pain/discomfort and anxiety/depression plus a visual analog scale rating "health today" with anchors ranging from 0 (worst imaginable health state) to 100 (best imaginable health state).
Timepoint [5] 0 0
Baseline up to Week 28
Secondary outcome [6] 0 0
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 will be assessed.
Timepoint [6] 0 0
Baseline up to Week 28

Eligibility
Key inclusion criteria
- 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
Minimum age
18 Years
Maximum age
80 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Acute pulmonary embolism within 6 months prior to or during Screening

- Planned (during the double-blind period of the study) balloon pulmonary angioplasty
(BPA)

- 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 DB period of the study

- Decompensated cardiac failure if not under close supervision

- 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, or inhaled prostacyclins / prostacyclin analogs,
or investigational treatment within 90 days prior to Randomization

- Administration of riociguat within 90 days prior to Randomization (if its use as
background medication becomes permissible based on pharmacokinetic Drug-drug
interaction [DDI] data during the conduct of the study, this exclusion criterion will
no longer apply)

- Change in dose or initiation of Phosphodiesterase type-5 (PDE-5) inhibitors, oral
prostacyclins / prostacyclin analogues, prostacyclin receptor agonists (or riociguat,
if its use becomes permissible during the study) within 90 days prior to Randomization
or anticipated during the 52-week 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Queensland Lung Transplant Service - Chermside
Recruitment hospital [2] 0 0
St Vincent's hospital - Darlinghurst
Recruitment postcode(s) [1] 0 0
4032 - Chermside
Recruitment postcode(s) [2] 0 0
2010 - Darlinghurst
Recruitment outside Australia
Country [1] 0 0
United States of America
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California
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Colorado
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Florida
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Illinois
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Kentucky
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Maryland
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Massachusetts
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Minnesota
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Nebraska
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Nevada
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New Mexico
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New York
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Ohio
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Oregon
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Pennsylvania
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United States of America
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Texas
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Argentina
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Buenos Aires
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Argentina
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Córdoba
Country [19] 0 0
Argentina
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Santa Fe
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Austria
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Graz
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Austria
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Linz
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Austria
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Vienna
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Bulgaria
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Sofia
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Canada
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Alberta
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Canada
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Ontario
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Colombia
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Bogota
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Colombia
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Cali
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Colombia
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Medellin
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Czechia
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Praha 2
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Germany
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Berlin
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Germany
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Bonn
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Germany
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Giessen
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Germany
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Hamburg
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Hannover
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Heidelberg
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Homburg
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Jena
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München
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Hungary
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Budapest
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Hungary
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Szeged
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Israel
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Haifa
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Israel
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Tel Aviv
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Israel
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Tel-Hashomer
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Italy
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Chieti
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Italy
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Pavia
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Italy
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Roma
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Torino
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Japan
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Hiroshima
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Sapporo
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Korea, Republic of
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Busan
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Seoul
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Lithuania
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Kaunas
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Vilnius
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Ciudad De México
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Lublin
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Wroclaw
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Bucuresti
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Tg. Mures
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Kazan
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Moscow
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Novosibirsk
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Saint-Petersburg
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Volgograd
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Saudi Arabia
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Jeddah
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Saudi Arabia
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Riyadh
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Serbia
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Belgrade
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Serbia
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Sremska Kamenica
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Singapore
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Singapore
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Slovakia
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Bratislava
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Spain
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Barcelona
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Madrid
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Toledo
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Valladolid
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Taiwan
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Kaohsiung
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Taipei
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Taiwan
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Taoyuan
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Turkey
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Adana
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Ankara
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Turkey
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Denizli
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Istanbul
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Turkey
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Izmir
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Turkey
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Kartal-Istanbul
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Turkey
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Mersin
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Ukraine
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Cherkasy
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Ukraine
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Dnipro
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Ukraine
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Kyiv
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Ukraine
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Lviv
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Ukraine
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Ternopil
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United Kingdom
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Cambridge
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United Kingdom
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London
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United Kingdom
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Newcastle Upon Tyne
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United Kingdom
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Sheffield

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Actelion
Address
Country

Ethics approval
Ethics application status

Summary
Brief 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).
Trial website
https://clinicaltrials.gov/show/NCT04271475
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Actelion Clinical Trial
Address 0 0
Actelion
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Study Contact
Address 0 0
Country 0 0
Phone 0 0
844-434-4210
Fax 0 0
Email 0 0
JNJ.CT@sylogent.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT04271475