Trial · NCT02558231
The Efficacy and Safety of Initial Triple Versus Initial Dual Oral Combination Therapy in Patients With Newly Diagnosed Pulmonary Arterial Hypertension
NCT02558231, Phase 3, Completed, Actelion; results first posted 2020-09-11
3 sourcestrials-2026-11-12-0.5.0
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ConductScience Library. The Efficacy and Safety of Initial Triple Versus Initial Dual Oral Combination Therapy in Patients With Newly Diagnosed Pulmonary Arterial Hypertension. Trials, record NCT02558231. Release trials-2026-11-12-0.5.0, 12 Nov 2026. https://conductscience.org/library/trials/NCT02558231
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Trial
As registered on ClinicalTrials.gov, in the graph's capture of the registry.
- Title
- The Efficacy and Safety of Initial Triple Versus Initial Dual Oral Combination Therapy in Patients With Newly Diagnosed Pulmonary Arterial Hypertension
- NCT number
- NCT02558231
- Status
- Completed
- Phases
- Phase 3
- Enrollment
- 247 participants, actual
- Lead sponsor
- Actelion
- Conditions
- Pulmonary Arterial Hypertension
- Interventions
- Macitentan, Tadalafil, Selexipag
- First posted
- 2015-09-23
- Last updated
- 2025-03-30
- Results first posted
- 2020-09-11
- Limitations and caveats
The main limitation of the sponsor's findings was that analyses of disease progression and mortality were exploratory due to the testing hierarchy and the post hoc nature of the analyses. The study was not powered to show significant differences for the disease progression related endpoint. Another limitation was the availability of hemodynamic assessments only for Week 26 timepoint.
Source ClinicalTrials.gov
Registered outcomes10
Each outcome the trial registered, primary first, in ClinicalTrials.gov's words.
| List | Outcome | Time frame | Description |
|---|---|---|---|
| Primary | Change From Baseline to Week 26 in Pulmonary Vascular Resistance (PVR) | Baseline, Week 26 | Change from baseline to Week 26 in PVR was expressed as the ratio of Week 26 to baseline PVR value (Week 26 divided by baseline) using re-calculated PVR. PVR was determined by right heart catheterization (RHC). A geometric least square mean ratio of Week 26 to baseline PVR less than (\<) 1 corresponds to a reduction in PVR from baseline. Missing values were imputed using a last observation carried forward (LOCF) approach. |
| Secondary | Change From Baseline to Week 26 in 6-minute Walk Distance (6MWD) | Baseline, Week 26 | The change from baseline to Week 26 in 6MWD was calculated as Week 26 minus baseline. The 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. Missing values were imputed using a LOCF approach. |
| Secondary | Change From Baseline to Week 26 in N-terminal Pro B-type Natriuretic Peptide (NT-proBNP) Levels | Baseline, Week 26 | The change from baseline to Week 26 in NT-proBNP was expressed as the ratio of Week 26 to baseline NT-proBNP (Week 26 divided by baseline). A geometric least square mean ratio of Week 26 to baseline NT-proBNP \<1 corresponds to a reduction in NT-proBNP from baseline. Missing values were imputed using a LOCF approach. |
| Secondary | Percentage of Participants With Absence of Worsening From Baseline to Week 26 in World Health Organization (WHO) Functional Class (FC) | Week 26 | WHO FC is a classification graded from Class I to IV which reflects disease severity based on symptoms. Worsening was defined as death or hospitalization due to PAH. Class I: No limitation of activity; Class II: slight limitation with ordinary activities; Class III: may not have symptoms at rest but greatly limited activities; Class IV: symptoms at rest and inability to carry out any physical activity without symptoms. Missing values were imputed using a LOCF approach. |
| Secondary | Change From Baseline to Week 26 in Mean Pulmonary Arterial Pressure (mPAP) | Baseline, Week 26 | Change from baseline to Week 26 in mean Pulmonary Arterial Pressure (mPAP) was measured. The pulmonary artery pressure is a measure of the blood pressure found in the main pulmonary artery. Missing values were imputed using a LOCF approach. |
| Secondary | Change From Baseline to Week 26 in Mean Right Atrial Pressure (mRAP) | Baseline, Week 26 | Change from baseline to Week 26 in mean Right Atrial Pressure (mRAP) was measured. Missing values were imputed using a LOCF approach. |
| Secondary | Change From Baseline to Week 26 in Total Pulmonary Resistance | Baseline, Week 26 | Change from baseline to Week 26 in total pulmonary resistance was measured. Total pulmonary resistance was calculated as mPAP/CO\*80, where CO is cardiac output. Re-calculated values were used for analysis and missing values were imputed using a LOCF approach. |
| Secondary | Change From Baseline to Week 26 in Cardiac Index | Baseline, Week 26 | Change from baseline to Week 26 in cardiac index was measured. Cardiac index is the amount of blood pumped by the heart, per minute, per meter square of body surface area. Re-calculated values were used for analysis and missing values were imputed using a LOCF approach. |
| Secondary | Change From Baseline to Week 26 in Venous Oxygen Saturation (%) | Baseline, Week 26 | Change from baseline to Week 26 in venous oxygen saturation was measured. Missing values were imputed using a LOCF approach. |
| Secondary | Number of Participants With Disease Progression Event | Week 26, Month 12, Month 18, Month 24, Month 30, and End of Analysis Period (up to 40 months) | Number of participants with disease progression event were reported. Disease progression event as adjudicated by the CEC, defined as any of the following: a. Death (all causes; adjudicated for PAH relationship); b. Hospitalization for worsening PAH; c. Initiation of prostacyclin, a prostacyclin analog, or a prostacyclin receptor agonist for worsening PAH; d. Clinical worsening defined as a post-baseline decrease in 6MWD by more than (\>) 15 percent (%) from the highest 6MWD obtained at or after baseline, accompanied by WHO FC III or IV (both conditions confirmed at two consecutive post-baseline visits separated by 1-21 days). |
Source ClinicalTrials.gov
Outcomes10
Each outcome the trial posted results for, in ClinicalTrials.gov's words.
| Type | Outcome | Time frame | Population | Units | Measured as |
|---|---|---|---|---|---|
| PRIMARY | Change From Baseline to Week 26 in Pulmonary Vascular Resistance (PVR) | Baseline, Week 26 | Full analysis set (FAS) included all randomized participants. | ratio | GEOMETRIC_LEAST_SQUARES_MEAN |
| SECONDARY | Change From Baseline to Week 26 in 6-minute Walk Distance (6MWD) | Baseline, Week 26 | Full analysis set included all randomized participants. Here, N (number of participants analyzed) signifies the number of participants analyzed for this outcome measure. | meter | LEAST_SQUARES_MEAN |
| SECONDARY | Change From Baseline to Week 26 in N-terminal Pro B-type Natriuretic Peptide (NT-proBNP) Levels | Baseline, Week 26 | Full analysis set included all randomized participants. Here, N (number of participants analyzed) signifies the number of participants analyzed for this outcome measure. | ratio | GEOMETRIC_LEAST_SQUARES_MEAN |
| SECONDARY | Percentage of Participants With Absence of Worsening From Baseline to Week 26 in World Health Organization (WHO) Functional Class (FC) | Week 26 | FAS included all randomized participants. Here, N (number of participants analyzed) signifies number of participants analyzed for this outcome measure. Participants with WHO FC IV at baseline were excluded from this analysis as they could not shift to a worse category. | percentage of participants | NUMBER |
| SECONDARY | Change From Baseline to Week 26 in Mean Pulmonary Arterial Pressure (mPAP) | Baseline, Week 26 | Full analysis set included all randomized participants. | millimeters of mercury (mmHg) | LEAST_SQUARES_MEAN |
| SECONDARY | Change From Baseline to Week 26 in Mean Right Atrial Pressure (mRAP) | Baseline, Week 26 | Full analysis set included all randomized participants. Here, N (number of participants analyzed) signifies the number of participants analyzed for this outcome measure. | mmHg | LEAST_SQUARES_MEAN |
| SECONDARY | Change From Baseline to Week 26 in Total Pulmonary Resistance | Baseline, Week 26 | Full analysis set included all randomized participants. | dynes*second per centimeter^5 | LEAST_SQUARES_MEAN |
| SECONDARY | Change From Baseline to Week 26 in Cardiac Index | Baseline, Week 26 | Full analysis set included all randomized participants. | liters per minute per meter square | LEAST_SQUARES_MEAN |
| SECONDARY | Change From Baseline to Week 26 in Venous Oxygen Saturation (%) | Baseline, Week 26 | Full analysis set included all randomized participants. Here, N (number of participants analyzed) signifies the number of participants analyzed for this outcome measure. | percentage of oxygen saturation | LEAST_SQUARES_MEAN |
| SECONDARY | Number of Participants With Disease Progression Event | Week 26, Month 12, Month 18, Month 24, Month 30, and End of Analysis Period (up to 40 months) | Full analysis set included all randomized participants. | Participants | COUNT_OF_PARTICIPANTS |
Source ClinicalTrials.gov
Results by group30
Each measurement the trial posted, group by group, in the words and numbers it posted.
| Outcome | Group | Category | Value | Spread | Units |
|---|---|---|---|---|---|
| Change From Baseline to Week 26 in Pulmonary Vascular Resistance (PVR) | Triple Oral Therapy (Macitentan, Tadalafil, and Selexipag) | 0.46 | 95% Confidence Interval 0.422 to 0.503 | ratio | |
| Change From Baseline to Week 26 in Pulmonary Vascular Resistance (PVR) | Double Oral Therapy (Macitentan, Tadalafil, and Placebo) | 0.48 | 95% Confidence Interval 0.441 to 0.526 | ratio | |
| Change From Baseline to Week 26 in 6-minute Walk Distance (6MWD) | Triple Oral Therapy (Macitentan, Tadalafil, and Selexipag) | 54.96 | 95% Confidence Interval 40.419 to 69.501 | meter | |
| Change From Baseline to Week 26 in 6-minute Walk Distance (6MWD) | Double Oral Therapy (Macitentan, Tadalafil, and Placebo) | 56.39 | 95% Confidence Interval 41.447 to 71.327 | meter | |
| Change From Baseline to Week 26 in N-terminal Pro B-type Natriuretic Peptide (NT-proBNP) Levels | Triple Oral Therapy (Macitentan, Tadalafil, and Selexipag) | 0.26 | 95% Confidence Interval 0.206 to 0.328 | ratio | |
| Change From Baseline to Week 26 in N-terminal Pro B-type Natriuretic Peptide (NT-proBNP) Levels | Double Oral Therapy (Macitentan, Tadalafil, and Placebo) | 0.25 | 95% Confidence Interval 0.200 to 0.320 | ratio | |
| Percentage of Participants With Absence of Worsening From Baseline to Week 26 in World Health Organization (WHO) Functional Class (FC) | Triple Oral Therapy (Macitentan, Tadalafil, and Selexipag) | 99.2 | percentage of participants | ||
| Percentage of Participants With Absence of Worsening From Baseline to Week 26 in World Health Organization (WHO) Functional Class (FC) | Double Oral Therapy (Macitentan, Tadalafil, and Placebo) | 97.5 | percentage of participants | ||
| Change From Baseline to Week 26 in Mean Pulmonary Arterial Pressure (mPAP) | Triple Oral Therapy (Macitentan, Tadalafil, and Selexipag) | -12.92 | 95% Confidence Interval -14.609 to -11.235 | millimeters of mercury (mmHg) | |
| Change From Baseline to Week 26 in Mean Pulmonary Arterial Pressure (mPAP) | Double Oral Therapy (Macitentan, Tadalafil, and Placebo) | -12.20 | 95% Confidence Interval -13.881 to -10.515 | millimeters of mercury (mmHg) |
1 to 10 of 30Source ClinicalTrials.gov
See all 30 results by groupParticipant flow8
How many started, completed or left each group, period by period.
| Period | Milestone | Group | Participants | Units counted |
|---|---|---|---|---|
| Overall Study | STARTED | Triple Oral Therapy (Macitentan, Tadalafil, and Selexipag) | 123 | |
| Overall Study | STARTED | Double Oral Therapy (Macitentan, Tadalafil, and Placebo) | 124 | |
| Overall Study | Treated | Triple Oral Therapy (Macitentan, Tadalafil, and Selexipag) | 123 | |
| Overall Study | Treated | Double Oral Therapy (Macitentan, Tadalafil, and Placebo) | 123 | |
| Overall Study | COMPLETED | Triple Oral Therapy (Macitentan, Tadalafil, and Selexipag) | 98 | |
| Overall Study | COMPLETED | Double Oral Therapy (Macitentan, Tadalafil, and Placebo) | 98 | |
| Overall Study | NOT COMPLETED | Triple Oral Therapy (Macitentan, Tadalafil, and Selexipag) | 25 | |
| Overall Study | NOT COMPLETED | Double Oral Therapy (Macitentan, Tadalafil, and Placebo) | 26 |
Source ClinicalTrials.gov
Adverse events488
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 | Triple Oral Therapy (Macitentan, Tadalafil, and Selexipag) | 14 | 119 | |
| other | Anaemia | Blood and lymphatic system disorders | Double Oral Therapy (Macitentan, Tadalafil, and Placebo) | 11 | 127 | |
| other | Iron Deficiency Anaemia | Blood and lymphatic system disorders | Triple Oral Therapy (Macitentan, Tadalafil, and Selexipag) | 6 | 119 | |
| other | Iron Deficiency Anaemia | Blood and lymphatic system disorders | Double Oral Therapy (Macitentan, Tadalafil, and Placebo) | 5 | 127 | |
| other | Palpitations | Cardiac disorders | Triple Oral Therapy (Macitentan, Tadalafil, and Selexipag) | 14 | 119 | |
| other | Palpitations | Cardiac disorders | Double Oral Therapy (Macitentan, Tadalafil, and Placebo) | 11 | 127 | |
| other | Abdominal Distension | Gastrointestinal disorders | Triple Oral Therapy (Macitentan, Tadalafil, and Selexipag) | 6 | 119 | |
| other | Abdominal Distension | Gastrointestinal disorders | Double Oral Therapy (Macitentan, Tadalafil, and Placebo) | 4 | 127 | |
| other | Abdominal Pain | Gastrointestinal disorders | Triple Oral Therapy (Macitentan, Tadalafil, and Selexipag) | 7 | 119 | |
| other | Abdominal Pain | Gastrointestinal disorders | Double Oral Therapy (Macitentan, Tadalafil, and Placebo) | 6 | 127 |
1 to 10 of 488Source ClinicalTrials.gov
See all 488 adverse eventsAdverse event totals6
The totals the trial posted for each group.
| Total | Group | Affected | At risk |
|---|---|---|---|
| Total, all-cause mortality | Triple Oral Therapy (Macitentan, Tadalafil, and Selexipag) | 4 | 119 |
| Total, all-cause mortality | Double Oral Therapy (Macitentan, Tadalafil, and Placebo) | 12 | 127 |
| Total, other adverse events | Triple Oral Therapy (Macitentan, Tadalafil, and Selexipag) | 118 | 119 |
| Total, other adverse events | Double Oral Therapy (Macitentan, Tadalafil, and Placebo) | 119 | 127 |
| Total, serious adverse events | Triple Oral Therapy (Macitentan, Tadalafil, and Selexipag) | 58 | 119 |
| Total, serious adverse events | Double Oral Therapy (Macitentan, Tadalafil, and Placebo) | 48 | 127 |
Source ClinicalTrials.gov
Papers1
The papers the trial lists on ClinicalTrials.gov.
| PMID | Listed as |
|---|---|
| 34593120 | 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 comparisons2
Comparisons of the trial's two groups, calculated by ConductScience from the counts it posted.
| Comparison | Source |
|---|---|
| Triple Oral Therapy (Macitentan, Tadalafil, and Selexipag) vs Double Oral Therapy (Macitentan, Tadalafil, and Placebo): deaths from any cause | Trial comparisons |
| Triple Oral Therapy (Macitentan, Tadalafil, and Selexipag) vs Double Oral Therapy (Macitentan, Tadalafil, and Placebo): serious adverse events | 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.
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.
For software
Read this trial from software.
The record and each of its lists are JSON, twenty rows a page. No key.
GET https://conductscience.org/api/trials/v1/NCT02558231
GET https://conductscience.org/api/trials/v1/NCT02558231/results?page=2