Trial · NCT03904693
Clinical Study to Compare the Efficacy and Safety of Macitentan and Tadalafil Monotherapies With the Corresponding Fixed-dose Combination Therapy in Subjects With Pulmonary Arterial Hypertension (PAH)
NCT03904693, Phase 3, Completed, Actelion; results first posted 2023-11-13
3 sourcestrials-2026-11-12-0.4.0
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ConductScience Library. Clinical Study to Compare the Efficacy and Safety of Macitentan and Tadalafil Monotherapies With the Corresponding Fixed-dose Combination Therapy in Subjects With Pulmonary Arterial Hypertension (PAH). Trials, record NCT03904693. Release trials-2026-11-12-0.4.0, 12 Nov 2026. https://conductscience.org/library/trials/NCT03904693
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Trial
As registered on ClinicalTrials.gov, in the graph's capture of the registry.
- Title
- Clinical Study to Compare the Efficacy and Safety of Macitentan and Tadalafil Monotherapies With the Corresponding Fixed-dose Combination Therapy in Subjects With Pulmonary Arterial Hypertension (PAH)
- NCT number
- NCT03904693
- Status
- Completed
- Phases
- Phase 3
- Enrollment
- 187 participants, actual
- Lead sponsor
- Actelion
- Conditions
- Pulmonary Arterial Hypertension (PAH) (WHO Group 1 PH)
- Interventions
- FDC macitentan/tadalafil, Macitentan 10 mg, Tadalafil 40 mg, Placebo FDC, Placebo macitentan, Placebo tadalafil
- First posted
- 2019-04-05
- Last updated
- 2025-12-19
- Other registries' IDs
- eudract:2014-004786-25
- Results first posted
- 2023-11-13
Source ClinicalTrials.gov
Registered outcomes5
Each outcome the trial registered, primary first, in ClinicalTrials.gov's words.
| List | Outcome | Time frame | Description |
|---|---|---|---|
| Primary | Change in Pulmonary Vascular Resistance (PVR) Expressed as the Ratio of Geometric Means of End of Double-blind Treatment (EDBT) to Baseline | Baseline, EDBT (up to 16 weeks) | Change in PVR expressed as the ratio of geometric means of EDBT to baseline were reported. |
| Secondary | Change From Baseline to EDBT in 6-minutes Walking Distance (6MWD) | Baseline, EDBT (Week 16) | Change from baseline to EDBT in 6MWD were reported. 6MWD was measured by 6-minute walk test (6MWT). The 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 | Change From Baseline in Pulmonary Arterial Hypertension Symptoms and Impact (PAH-SYMPACT) in Cardiopulmonary Symptom Domain Scores to EDBT | Baseline, EDBT (Week 16) | Change from baseline in PAH-SYMPACT in cardiopulmonary symptom domain scores to EDBT were reported. PAH-SYMPACT was a pulmonary arterial hypertension (PAH)-specific patient-reported outcomes questionnaire that consists of 11 symptoms items, 11 impacts items and 1 item on oxygen use. The symptom items were divided into cardiopulmonary and cardiovascular domains, and the impact items were divided into physical and emotional/cognitive domains. Cardiopulmonary symptoms contain 6 items; shortness of breath, fatigue, lack of energy, swelling in ankles or legs, swelling in stomach area, and cough. Scores for the individual items were reported on a 5-point Likert scale, ranging from 0 (no symptom at all) to 4 (very severe symptoms), with higher scores indicated greater symptom severity. |
| Secondary | Change From Baseline in Pulmonary Arterial Hypertension Symptoms and Impact (PAH-SYMPACT) in Cardiovascular Symptom Domain Scores to EDBT | Baseline, EDBT (Week 16) | Change from baseline in PAH-SYMPACT in cardiovascular symptom domain scores to EDBT were reported. PAH-SYMPACT is a PAH-specific patient-reported outcomes questionnaire that consists of 11 symptoms items, 11 impacts items and 1 item on oxygen use. The symptom items were divided into cardiopulmonary and cardiovascular domains, and the impact items were divided into physical and emotional/cognitive domains. Cardiovascular symptoms contain 5 items; heart palpitations (heart fluttering), rapid heartbeat, chest pain, chest tightness, and lightheadedness. Scores for the individual items were reported on a 5-point Likert scale, ranging from 0 (no symptom at all) to 4 (very severe symptom), with higher scores indicated greater symptom severity. |
| Secondary | Percentage of Participants With Absence of Worsening in World Health Organization (WHO) Functional Class (FC) From Baseline at EDBT | At Week 16 (EDBT) | Percentage of participants with absence of worsening in FC from baseline to EDBT were reported. The study was adaptive with two stages: Stage 1 and Stage 2. WHO functional classification (FC), PAH range from Class I (no limitation in physical activity, no dyspnea or fatigue, chest pain, or near syncope with normal activity), Class II (slight limitation of physical activity), Class III (marked limitation of physical activity), Class IV (cannot perform a physical activity without any symptoms, dyspnea and/or fatigue at rest). |
Source ClinicalTrials.gov
Outcomes5
Each outcome the trial posted results for, in ClinicalTrials.gov's words.
| Type | Outcome | Time frame | Population | Units | Measured as |
|---|---|---|---|---|---|
| PRIMARY | Change in Pulmonary Vascular Resistance (PVR) Expressed as the Ratio of Geometric Means of End of Double-blind Treatment (EDBT) to Baseline | Baseline, EDBT (up to 16 weeks) | The full analysis set (FAS) included all randomized participants who received at least one dose of study treatment (for participants on FDC, at least one dose of either macitentan or tadalafil). Treatment-naive participants randomized to both M/T FDC arms (ERA and PDE-5i strata) are counted twice as per planned analysis. | Ratio | GEOMETRIC_MEAN |
| SECONDARY | Change From Baseline to EDBT in 6-minutes Walking Distance (6MWD) | Baseline, EDBT (Week 16) | The FAS included all randomized participants who received at least one dose of study treatment (for participants on FDC, at least one dose of either macitentan or tadalafil). Treatment-naive participants randomized to both macitentan 10 mg and tadalafil 40 mg fixed-dose combination (M/T FDC) arms (ERA and PDE-5i strata) are counted twice as per planned analysis. | Meters | MEAN |
| SECONDARY | Change From Baseline in Pulmonary Arterial Hypertension Symptoms and Impact (PAH-SYMPACT) in Cardiopulmonary Symptom Domain Scores to EDBT | Baseline, EDBT (Week 16) | The PAH-SYMPACT symptoms analysis set included all participants included in the FAS for whom at least one baseline value of symptoms domain was provided. Treatment-naive participants randomized to both M/T FDC arms (ERA and PDE-5i strata) were counted twice as per planned analysis. | Score on a scale | MEAN |
| SECONDARY | Change From Baseline in Pulmonary Arterial Hypertension Symptoms and Impact (PAH-SYMPACT) in Cardiovascular Symptom Domain Scores to EDBT | Baseline, EDBT (Week 16) | The PAH-SYMPACT symptoms analysis set included all participants included in the FAS for whom at least one baseline value of symptoms domain was provided. Treatment-naive participants randomized to both M/T FDC arms (ERA and PDE-5i strata) were counted twice as per planned analysis. | Score on a scale | MEAN |
| SECONDARY | Percentage of Participants With Absence of Worsening in World Health Organization (WHO) Functional Class (FC) From Baseline at EDBT | At Week 16 (EDBT) | The FAS included all randomized participants who received at least one dose of study treatment (for participants on FDC, at least one dose of either macitentan or tadalafil). Treatment-naive participants randomized to both M/T FDC arms (ERA and PDE-5i strata) are counted twice as per planned analysis. Here, 'N' overall (number of participants analyzed) signifies the number of participants evaluable, n (number analyzed) =number of participants evaluable for specified category. | Percentage of participants | NUMBER |
Source ClinicalTrials.gov
Results by group56
Each measurement the trial posted, group by group, in the words and numbers it posted.
| Outcome | Group | Category | Value | Spread | Units |
|---|---|---|---|---|---|
| Change in Pulmonary Vascular Resistance (PVR) Expressed as the Ratio of Geometric Means of End of Double-blind Treatment (EDBT) to Baseline | DB: Treatment-naive And Prior ERA Strata: Macitentan Monotherapy 10 Milligrams (mg) | 0.77 | 95% Confidence Interval 0.69 to 0.87 | Ratio | |
| Change in Pulmonary Vascular Resistance (PVR) Expressed as the Ratio of Geometric Means of End of Double-blind Treatment (EDBT) to Baseline | DB: Treatment-naive And Prior ERA Strata: M/T FDC | 0.55 | 95% Confidence Interval 0.50 to 0.60 | Ratio | |
| Change in Pulmonary Vascular Resistance (PVR) Expressed as the Ratio of Geometric Means of End of Double-blind Treatment (EDBT) to Baseline | DB: Treatment-naive And Prior PDE-5i Strata: Tadalafil Monotherapy 20 mg (2 Tablets*20 mg) | 0.78 | 95% Confidence Interval 0.72 to 0.84 | Ratio | |
| Change in Pulmonary Vascular Resistance (PVR) Expressed as the Ratio of Geometric Means of End of Double-blind Treatment (EDBT) to Baseline | DB: Treatment-naive And Prior PDE-5i Strata: M/T FDC | 0.56 | 95% Confidence Interval 0.52 to 0.60 | Ratio | |
| Change From Baseline to EDBT in 6-minutes Walking Distance (6MWD) | DB: Treatment-naive And Prior ERA Strata: Macitentan 10 Milligrams (mg) | 38.5 | Standard Deviation 70.42 | Meters | |
| Change From Baseline to EDBT in 6-minutes Walking Distance (6MWD) | DB: Treatment-naive And Prior ERA Strata: M/T FDC | 52.9 | Standard Deviation 88.23 | Meters | |
| Change From Baseline to EDBT in 6-minutes Walking Distance (6MWD) | DB: Treatment-naive And Prior PDE-5i Strata: Tadalafil Monotherapy 20 mg (2 Tablets*20 mg) | 15.9 | Standard Deviation 45.04 | Meters | |
| Change From Baseline to EDBT in 6-minutes Walking Distance (6MWD) | DB: Treatment-naive And Prior PDE-5i Strata: M/T FDC | 43.4 | Standard Deviation 78.03 | Meters | |
| Change From Baseline in Pulmonary Arterial Hypertension Symptoms and Impact (PAH-SYMPACT) in Cardiopulmonary Symptom Domain Scores to EDBT | DB: Treatment-naive And Prior ERA Strata: Macitentan 10 Milligrams (mg) | -0.14 | Standard Deviation 0.478 | Score on a scale | |
| Change From Baseline in Pulmonary Arterial Hypertension Symptoms and Impact (PAH-SYMPACT) in Cardiopulmonary Symptom Domain Scores to EDBT | DB: Treatment-naive And Prior ERA Strata: M/T FDC | -0.20 | Standard Deviation 0.394 | Score on a scale |
1 to 10 of 56Source ClinicalTrials.gov
See all 56 results by groupParticipant flow54
How many started, completed or left each group, period by period.
| Period | Milestone | Group | Participants | Units counted |
|---|---|---|---|---|
| DB Treatment Period (Week 1 to Week 16) | STARTED | DB: Treatment-naive and Prior ERA Strata: Macitentan Monotherapy 10 Milligrams (mg) | 35 | |
| DB Treatment Period (Week 1 to Week 16) | STARTED | DB: Treatment-naive and Prior PDE-5i Strata: Tadalafil Monotherapy 20 mg (2 Tablets*20 mg) | 44 | |
| DB Treatment Period (Week 1 to Week 16) | STARTED | DB: Treatment-naive and Prior ERA/ PDE-5i Strata: M/T FDC | 108 | |
| DB Treatment Period (Week 1 to Week 16) | STARTED | OL: Treatment-naive and Prior ERA Strata: M/T FDC | 0 | |
| DB Treatment Period (Week 1 to Week 16) | STARTED | OL: Treatment-naive and Prior PDE-5i Strata: M/T FDC | 0 | |
| DB Treatment Period (Week 1 to Week 16) | STARTED | OL: Treatment-naive and Prior ERA/ PDE-5i Strata: M/T FDC | 0 | |
| DB Treatment Period (Week 1 to Week 16) | Treated (Safety Analysis Set) | DB: Treatment-naive and Prior ERA Strata: Macitentan Monotherapy 10 Milligrams (mg) | 35 | |
| DB Treatment Period (Week 1 to Week 16) | Treated (Safety Analysis Set) | DB: Treatment-naive and Prior PDE-5i Strata: Tadalafil Monotherapy 20 mg (2 Tablets*20 mg) | 44 | |
| DB Treatment Period (Week 1 to Week 16) | Treated (Safety Analysis Set) | DB: Treatment-naive and Prior ERA/ PDE-5i Strata: M/T FDC | 107 | |
| DB Treatment Period (Week 1 to Week 16) | Treated (Safety Analysis Set) | OL: Treatment-naive and Prior ERA Strata: M/T FDC | 0 |
1 to 10 of 54Source ClinicalTrials.gov
See all 54 participant flowAdverse events1,000
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 | Events |
|---|---|---|---|---|---|---|
| other | Anaemia | Blood and lymphatic system disorders | DB: Treatment-naive and Prior ERA Strata: Macitentan Monotherapy 10 Milligrams (mg) | 0 | 35 | |
| other | Anaemia | Blood and lymphatic system disorders | DB: Treatment-naive And Prior ERA Strata: M/T FDC | 6 | 70 | |
| other | Anaemia | Blood and lymphatic system disorders | DB: Treatment-naive And Prior PDE-5i Strata: Tadalafil Monotherapy 20 mg (2 Tablets*20 mg) | 0 | 44 | |
| other | Anaemia | Blood and lymphatic system disorders | DB: Treatment-naive And Prior PDE-5i Strata: M/T FDC | 6 | 86 | |
| other | Anaemia | Blood and lymphatic system disorders | DB: Treatment-naive and Prior ERA/ PDE-5i Strata: M/T FDC | 8 | 107 | |
| other | Anaemia | Blood and lymphatic system disorders | OL: Treatment-naive and Prior ERA Strata: M/T FDC | 4 | 35 | |
| other | Anaemia | Blood and lymphatic system disorders | OL: Treatment-naive and Prior PDE-5i Strata: M/T FDC | 5 | 43 | |
| other | Anaemia | Blood and lymphatic system disorders | DB + OL: Treatment-naive and Prior ERA/ PDE-5i Strata: M/T FDC | 13 | 107 | |
| other | Iron Deficiency Anaemia | Blood and lymphatic system disorders | DB: Treatment-naive and Prior ERA Strata: Macitentan Monotherapy 10 Milligrams (mg) | 1 | 35 | |
| other | Iron Deficiency Anaemia | Blood and lymphatic system disorders | DB: Treatment-naive And Prior ERA Strata: M/T FDC | 2 | 70 |
1 to 10 of 1,000Source ClinicalTrials.gov
See all 1,000 adverse eventsAdverse event totals24
The totals the trial posted for each group.
| Total | Group | Affected | At risk |
|---|---|---|---|
| Total, all-cause mortality | DB: Treatment-naive and Prior ERA Strata: Macitentan Monotherapy 10 Milligrams (mg) | 0 | 35 |
| Total, all-cause mortality | DB: Treatment-naive And Prior ERA Strata: M/T FDC | 2 | 71 |
| Total, all-cause mortality | DB: Treatment-naive And Prior PDE-5i Strata: Tadalafil Monotherapy 20 mg (2 Tablets*20 mg) | 0 | 44 |
| Total, all-cause mortality | DB: Treatment-naive And Prior PDE-5i Strata: M/T FDC | 2 | 87 |
| Total, all-cause mortality | DB: Treatment-naive and Prior ERA/ PDE-5i Strata: M/T FDC | 3 | 108 |
| Total, all-cause mortality | OL: Treatment-naive and Prior ERA Strata: M/T FDC | 0 | 35 |
| Total, all-cause mortality | OL: Treatment-naive and Prior PDE-5i Strata: M/T FDC | 2 | 43 |
| Total, all-cause mortality | DB + OL: Treatment-naive and Prior ERA/ PDE-5i Strata: M/T FDC | 9 | 107 |
| Total, other adverse events | DB: Treatment-naive and Prior ERA Strata: Macitentan Monotherapy 10 Milligrams (mg) | 16 | 35 |
| Total, other adverse events | DB: Treatment-naive And Prior ERA Strata: M/T FDC | 49 | 70 |
1 to 10 of 24Source ClinicalTrials.gov
See all 24 adverse event totalsPapers3
The papers the trial lists on ClinicalTrials.gov.
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 comparisons0
Comparisons of the trial's two groups, calculated by ConductScience from the counts it posted.
None in this release.
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.
Data dates
The day each source was copied for this release.
Sources 3
- ClinicalTrials.gov's posted results, through CTTI's AACTFreely available. Acknowledgement requested
- ClinicalTrials.govNo license 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.
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