Trial · NCT04271475

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

NCT04271475, Phase 3, Terminated, Actelion; results first posted 2025-04-22

3 sourcestrials-2026-11-12-0.4.0

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ConductScience Library. A Study to Evaluate Efficacy and Safety of Macitentan 75 mg in Inoperable or Persistent/Recurrent Chronic Thromboembolic Pulmonary Hypertension. Trials, record NCT04271475. Release trials-2026-11-12-0.4.0, 12 Nov 2026. https://conductscience.org/library/trials/NCT04271475

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Trial

As registered on ClinicalTrials.gov, in the graph's capture of the registry.

Title: A Study to Evaluate Efficacy and Safety of Macitentan 75 mg in Inoperable or Persistent/Recurrent Chronic Thromboembolic Pulmonary Hypertension
NCT number: NCT04271475
Status: Terminated
Phases: Phase 3
Enrollment: 127 participants, actual
Lead sponsor: Actelion
Conditions: Chronic Thromboembolic Pulmonary Hypertension
Interventions: Macitentan, Placebo
First posted: 2020-02-17
Last updated: 2025-06-27
Other registries' IDs: eudract:2019-004131-24
Results first posted: 2025-04-22
Limitations and caveats: Limitations of the trial such as small numbers of participants analysed or technical problems leading to unreliable data.

Source ClinicalTrials.gov

Registered outcomes7

Each outcome the trial registered, primary first, in ClinicalTrials.gov's words.

List	Outcome	Time frame	Description
Primary	Change From Baseline in 6-minute Walk Distance (6MWD) at Week 28	Baseline (Day 1), 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.
Secondary	Time to First Clinical Event Committee (CEC) Confirmed Clinical Worsening up to End-of Double-blind-treatment (EODBT) Period	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	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.
Secondary	Number of Participants With Improvement in World Health Organization Functional Class (WHO FC) From Baseline to Week 28	From Baseline (Day 1) up 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.
Secondary	Change From Baseline to Week 28 in Pulmonary Arterial Hypertension - Symptoms and Impact (PAH-SYMPACT) - Cardiopulmonary Symptom Domain Score	From Baseline (Day 1) up to Week 28	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.
Secondary	Change From Baseline to Week 28 in PAH-SYMPACT - Cardiovascular Symptom Domain Score	From Baseline (Day 1) up to Week 28	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.
Secondary	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	From Baseline (Day 1) up to Week 28	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.
Secondary	Change From Baseline to Week 28 in Accelerometer-assessed Proportion of Time Spent in Moderate to Vigorous Physical Activity	From Baseline (Day 1) up to Week 28	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.

Source ClinicalTrials.gov

Outcomes7

Each outcome the trial posted results for, in ClinicalTrials.gov's words.

Type	Outcome	Time frame	Population	Units	Measured as
PRIMARY	Change From Baseline in 6-minute Walk Distance (6MWD) at Week 28	Baseline (Day 1), Week 28	Full analysis set (FAS) included all randomized participants assigned to a study intervention and were analyzed according to the intervention they had been assigned to via interactive web response system (IWRS). Here, 'N' (number of participants analyzed) signifies number of participants evaluable for this outcome measure.	Meters	LEAST_SQUARES_MEAN
SECONDARY	Time to First Clinical Event Committee (CEC) Confirmed Clinical Worsening up to End-of Double-blind-treatment (EODBT) Period	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	FAS included all randomized participants assigned to a study intervention and were analyzed according to the intervention they had been assigned to via IWRS.	Months	MEDIAN
SECONDARY	Number of Participants With Improvement in World Health Organization Functional Class (WHO FC) From Baseline to Week 28	From Baseline (Day 1) up to Week 28	FAS included all randomized participants assigned to a study intervention and were analyzed according to the intervention they had been assigned to via IWRS. Here, 'N' (number of participants analyzed) signifies number of participants evaluable for this outcome measure.	Participants	COUNT_OF_PARTICIPANTS
SECONDARY	Change From Baseline to Week 28 in Pulmonary Arterial Hypertension - Symptoms and Impact (PAH-SYMPACT) - Cardiopulmonary Symptom Domain Score	From Baseline (Day 1) up to Week 28	FAS included all randomized participants assigned to a study intervention and were analyzed according to the intervention they had been assigned to via IWRS. Here, 'N' (number of participants analyzed) signifies number of participants evaluable for this outcome measure.	score on a scale	MEAN
SECONDARY	Change From Baseline to Week 28 in PAH-SYMPACT - Cardiovascular Symptom Domain Score	From Baseline (Day 1) up to Week 28	FAS included all randomized participants assigned to a study intervention and were analyzed according to the intervention they had been assigned to via IWRS. Here, 'N' (number of participants analyzed) signifies number of participants evaluable for this outcome measure.	Score on a scale	MEAN
SECONDARY	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	From Baseline (Day 1) up to Week 28	FAS included all randomized participants assigned to a study intervention and were analyzed according to the intervention they had been assigned to via IWRS. Here, 'N' (number of participants analyzed) signifies number of participants evaluable for this outcome measure.	Score on a scale	MEAN
SECONDARY	Change From Baseline to Week 28 in Accelerometer-assessed Proportion of Time Spent in Moderate to Vigorous Physical Activity	From Baseline (Day 1) up to Week 28	FAS included all randomized participants assigned to a study intervention and were analyzed according to the intervention they had been assigned to via IWRS. Here, 'N' (number of participants analyzed) signifies number of participants evaluable for this outcome measure.	Percent of minutes per day	MEAN

Source ClinicalTrials.gov

Results by group16

Each measurement the trial posted, group by group, in the words and numbers it posted.

Outcome	Group	Value	Spread	Units
Change From Baseline in 6-minute Walk Distance (6MWD) at Week 28	Double Blind (DB) Period: Macitentan	9.7	Standard Error 5.81	Meters
Change From Baseline in 6-minute Walk Distance (6MWD) at Week 28	DB Period: Placebo	25.8	Standard Error 5.78	Meters
Time to First Clinical Event Committee (CEC) Confirmed Clinical Worsening up to End-of Double-blind-treatment (EODBT) Period	Double Blind (DB) Period: Macitentan	NA	95% Confidence Interval 19.0 to NA	Months
Time to First Clinical Event Committee (CEC) Confirmed Clinical Worsening up to End-of Double-blind-treatment (EODBT) Period	DB Period: Placebo	NA	95% Confidence Interval NA to NA	Months
Number of Participants With Improvement in World Health Organization Functional Class (WHO FC) From Baseline to Week 28	Double Blind (DB) Period: Macitentan	7		Participants
Number of Participants With Improvement in World Health Organization Functional Class (WHO FC) From Baseline to Week 28	DB Period: Placebo	6		Participants
Change From Baseline to Week 28 in Pulmonary Arterial Hypertension - Symptoms and Impact (PAH-SYMPACT) - Cardiopulmonary Symptom Domain Score	Double Blind (DB) Period: Macitentan	-0.089	Standard Deviation 0.5856	score on a scale
Change From Baseline to Week 28 in Pulmonary Arterial Hypertension - Symptoms and Impact (PAH-SYMPACT) - Cardiopulmonary Symptom Domain Score	DB Period: Placebo	-0.060	Standard Deviation 0.3767	score on a scale
Change From Baseline to Week 28 in PAH-SYMPACT - Cardiovascular Symptom Domain Score	Double Blind (DB) Period: Macitentan	-0.141	Standard Deviation 0.4530	Score on a scale
Change From Baseline to Week 28 in PAH-SYMPACT - Cardiovascular Symptom Domain Score	DB Period: Placebo	-0.101	Standard Deviation 0.2818	Score on a scale

1 to 10 of 16Source ClinicalTrials.gov

See all 16 results by group

Participant flow24

How many started, completed or left each group, period by period.

Period	Milestone	Group	Participants
DB Period: Day 1 up to EODBT	STARTED	Double Blind (DB) Period: Macitentan	64
DB Period: Day 1 up to EODBT	STARTED	DB Period: Placebo	63
DB Period: Day 1 up to EODBT	STARTED	Open Label (OL) Period: DB Macitentan	0
DB Period: Day 1 up to EODBT	STARTED	OL Period: DB Placebo	0
DB Period: Day 1 up to EODBT	COMPLETED	Double Blind (DB) Period: Macitentan	1
DB Period: Day 1 up to EODBT	COMPLETED	DB Period: Placebo	1
DB Period: Day 1 up to EODBT	COMPLETED	Open Label (OL) Period: DB Macitentan	0
DB Period: Day 1 up to EODBT	COMPLETED	OL Period: DB Placebo	0
DB Period: Day 1 up to EODBT	NOT COMPLETED	Double Blind (DB) Period: Macitentan	63
DB Period: Day 1 up to EODBT	NOT COMPLETED	DB Period: Placebo	62

1 to 10 of 24Source ClinicalTrials.gov

See all 24 participant flow

Adverse events276

Each adverse event the trial posted, group by group: the participants affected out of those at risk.

Type	Event	Organ system	Group	Affected	At risk
other	Anaemia	Blood and lymphatic system disorders	Double Blind (DB) Period: Macitentan	5	64
other	Anaemia	Blood and lymphatic system disorders	DB Period: Placebo	2	63
other	Anaemia	Blood and lymphatic system disorders	Open Label (OL) Period: DB Macitentan	0	1
other	Anaemia	Blood and lymphatic system disorders	OL Period: DB Placebo	1	6
other	Iron Deficiency Anaemia	Blood and lymphatic system disorders	Double Blind (DB) Period: Macitentan	6	64
other	Iron Deficiency Anaemia	Blood and lymphatic system disorders	DB Period: Placebo	2	63
other	Iron Deficiency Anaemia	Blood and lymphatic system disorders	Open Label (OL) Period: DB Macitentan	0	1
other	Iron Deficiency Anaemia	Blood and lymphatic system disorders	OL Period: DB Placebo	0	6
other	Palpitations	Cardiac disorders	Double Blind (DB) Period: Macitentan	2	64
other	Palpitations	Cardiac disorders	DB Period: Placebo	4	63

1 to 10 of 276Source ClinicalTrials.gov

See all 276 adverse events

Adverse event totals12

The totals the trial posted for each group.

Total	Group	Affected	At risk
Total, all-cause mortality	Double Blind (DB) Period: Macitentan	1	64
Total, all-cause mortality	DB Period: Placebo	0	63
Total, all-cause mortality	Open Label (OL) Period: DB Macitentan	0	1
Total, all-cause mortality	OL Period: DB Placebo	0	6
Total, other adverse events	Double Blind (DB) Period: Macitentan	47	64
Total, other adverse events	DB Period: Placebo	38	63
Total, other adverse events	Open Label (OL) Period: DB Macitentan	1	1
Total, other adverse events	OL Period: DB Placebo	5	6
Total, serious adverse events	Double Blind (DB) Period: Macitentan	17	64
Total, serious adverse events	DB Period: Placebo	14	63

1 to 10 of 12Source ClinicalTrials.gov

See all 12 adverse event totals

Papers1

The papers the trial lists on ClinicalTrials.gov.

PMID	Listed as
38945473	DERIVED

Source PubMed

Grants0

The grants NIH RePORTER links to the trial, newest funded first: NIH's, and some of AHRQ's, CDC's, FDA's and VA's. Each shows its title, principal investigators, organization and funder in its newest year.

None in this release.

Trial comparisons1

Comparisons of the trial's two groups, calculated by ConductScience from the counts it posted.

Comparison
Double Blind (DB) Period: Macitentan vs DB Period: Placebo: Number of Participants With Improvement in World Health Organization Functional Class (WHO FC) From Baseline to Week 28

Source Trial comparisons

Tests0

The ConductCognition tests this trial's registered outcomes name, as ScienceGraph matched them in trial-tests-2026-11-12-0.2.1.

None in this release.

Source

Release: trials-2026-11-12-0.4.0
Release manifest SHA-256: 0f4a8d8c48aee2a7573ae0fa94ecbeab70c1adbe449bbc95c424bc7d3e97b9d4
Registry capture: 2026-11-12
Results copy, AACT: 2026-03-23
NIH clinical studies file: 2026-11-13

Source ClinicalTrials.gov

Sources 3

ClinicalTrials.gov's posted results, through CTTI's AACTFreely available. Acknowledgement requested
ClinicalTrials.govNone stated
NIH RePORTER's clinical studies and project filesPublic domain

Each source's terms

ClinicalTrials.gov's posted results, through CTTI's AACTClinicalTrials.gov data via Aggregate Analysis of ClinicalTrials.gov (AACT), CTTI. CTTI makes its materials freely available and requests acknowledgement. https://aact.ctti-clinicaltrials.org/documentation/299
ClinicalTrials.govnone stated
NIH RePORTER's clinical studies and project filesPublic domain (NIH RePORTER)

ClinicalTrials.gov's data carry an international copyright outside the United States: https://clinicaltrials.gov/about-site/terms-conditions.

For software

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