Trial · NCT00303459
Effects of the Combination of Bosentan and Sildenafil Versus Sildenafil Monotherapy on Pulmonary Arterial Hypertension (PAH)
NCT00303459, Phase 4, Completed, Actelion; results first posted 2015-01-26
3 sourcestrials-2026-11-12-0.5.0
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ConductScience Library. Effects of the Combination of Bosentan and Sildenafil Versus Sildenafil Monotherapy on Pulmonary Arterial Hypertension (PAH). Trials, record NCT00303459. Release trials-2026-11-12-0.5.0, 12 Nov 2026. https://conductscience.org/library/trials/NCT00303459
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Trial
As registered on ClinicalTrials.gov, in the graph's capture of the registry.
- Title
- Effects of the Combination of Bosentan and Sildenafil Versus Sildenafil Monotherapy on Pulmonary Arterial Hypertension (PAH)
- NCT number
- NCT00303459
- Status
- Completed
- Phases
- Phase 4
- Enrollment
- 334 participants, actual
- Lead sponsor
- Actelion
- Conditions
- Pulmonary Arterial Hypertension
- Interventions
- bosentan, placebo
- First posted
- 2006-03-17
- Last updated
- 2025-02-04
- Results first posted
- 2015-01-26
Source ClinicalTrials.gov
Registered outcomes10
Each outcome the trial registered, primary first, in ClinicalTrials.gov's words.
| List | Outcome | Time frame | Description |
|---|---|---|---|
| Primary | Time to First Confirmed Morbidity/Mortality Event up to the End of Study | From baseline to end of study, approximately 86 months | Kaplan-Meier estimate of percentage of participants without a morbidity/mortality event. A morbidity/mortality event is defined as the occurrence of a) death, b) hospitalization for worsening or complication of PAH or intravenous prostanoid initiation, c) atrial septostomy, d) lung transplantation, or e) worsening PAH, defined as "moderately" or "markedly" worsened PAH symptoms using a patient global self-assessment (PGSA) scale AND initiation of inhaled or subcutaneous prostanoids or the disease progression package (open-label bosentan). If a patient replied "no change" or "mildly worse" on the PGSA, a decrease in 6MWT of 20% versus last visit or 30% versus baseline is also required to confirm the event. |
| Secondary | Time to First Confirmed Death, Hospitalization for Worsening or Complication of PAH or Initiation of Intravenous Prostanoids, Atrial Septostomy, or Lung Transplantation | Baseline to end of study, approximately 86 months | Kaplan-Meier estimate of percentage of participants without an event of death, hospitalization (for worsening or complication of PAH or initiation of intravenous prostanoids), atrial septostomy or lung transplantation. Time to first confirmed death, hospitalization (for worsening or complication of PAH or initiation of intravenous prostanoids), atrial septostomy or lung transplantation from baseline to end of study was confirmed by an independent Clinical Endpoint Committee. |
| Secondary | Change From Baseline to Week 16 in 6 Minute Walk Test (6MWT) | From baseline to week 16 | The 6MWT is a non-encouraged test, which measures the distance covered over a 6 minute walk; the patient is instructed to walk as far as possible in a 30 m long flat corridor, back and forth around two cones, with the permission to slow down, rest, or stop if needed. Areas were to be well ventilated with air temperature controlled between 20 °C and 23 °C (68 °F to 76 °F). The test was to be administered at the same time of day and by the same tester throughout the study. The tester measured the distance walked by non-encouraged patients during the timed 6 minute period. |
| Secondary | Number of Participants With Improved, No Change, or Worsened World Health Organisation Functional Class From Baseline to Week 16 | From baseline to Week 16 | Class I: no limitation of usual physical activity (PA) which does not increase dyspnea, fatigue, chest pain, or presyncope. Class II: mild limitation of PA. No discomfort at rest. Normal PA increases dyspnea, fatigue, chest pain, or presyncope. Class III: marked limitation of PA. No discomfort at rest. Less than ordinary activity increases dyspnea, fatigue, chest pain, or presyncope. Class IV: unable to perform any PA and who may have signs of right ventricular failure. Dyspnea and/or fatigue may be present at rest and symptoms are increased by almost any PA. |
| Secondary | Time to Death of All Causes From Baseline to End of Study | Baseline to End of Study, approximately 86 months | Kaplan-Meier estimate of percentage of participants without a mortality event.Time to death due to any cause. |
| Secondary | Adjusted Percentage Ratio From Baseline in N-terminal Pro-B-type Natriuretic Peptide (NT-pro-BNP) | Baseline to Month 20 | Blood sampling for the measurement of NT-pro-BNP was performed and the plasma concentrations of NT-pro-BNP were determined by a certified centralized laboratory. |
| Secondary | Change From Baseline to Week 16 in Borg Dyspnea Index | Baseline to Week 16 | The Borg dyspnea index was evaluated immediately after the 6MWT to obtain a rating of dyspnea at the end of the exercise using a scale from 0 ('Nothing at all') to 10 ('Very, very severe - maximal'). |
| Secondary | Change From Baseline to Week 16 in the EuroQol 5 Dimensions (EQ-5D) Questionnaire Calculated Score | From baseline to Week 16 | The EQ-5D questionnaire is a patient-reported outcome consisting of a 5 dimensional descriptive system and a visual analog scale (VAS). The descriptive system asks respondents to describe their health status. Health is defined in 5 dimensions: (1) mobility, (2) self care, (3) usual activities, (4) pain or discomfort, and (5) anxiety or depression. Each dimension is divided into 3 levels, indicating (a) no problem, (b) some or moderate problems, or (c) extreme problems. Respondents record their problem(s) in each of the 5 dimensions. Combinations of these levels define a total of 243 health states. A health state defined by the descriptive system of EQ-5D can be described by a 5-digit number with full health is indicated by 11111 and poorest health state by 33333. The EQ-5D calculated score was derived by re-assigning local scores for answers to each question and combining these local scores into a global score with ranges from 0 (worst possible outcome) to 1 (best possible outcome). |
| Secondary | Change From Baseline to Week 16 in the EuroQol 5 Dimensions (EQ-5D) Visual Analogue Scale Score | Baseline to Week 16 | The EQ-5D questionnaire is a patient-reported outcome consisting of a 5 dimensional descriptive system and a visual analog scale (VAS) together with brief demographic questions. EQ-5D VAS asks respondents to rate their perception of their overall health on a vertical visual analogue scale with 'best imaginable health state' set at 100 and 'worst imaginable health state' set at 0. |
| Secondary | Patient Global Self Assessment (PGSA) Status at Week 16 | Week 16 | The PGSA is a questionnaire that allows the patient to compare his/her PAH status in response to the question "How do you feel about your PAH today compared with your last visit?" asked by the investigator. Patients use a seven-point scale to respond: markedly better, moderately better, mildly better, no change, markedly worse, moderately worse, or mildly worse. |
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 | Time to First Confirmed Morbidity/Mortality Event up to the End of Study | From baseline to end of study, approximately 86 months | All randomized set | percentage of participants-Kaplan Meier | NUMBER |
| SECONDARY | Time to First Confirmed Death, Hospitalization for Worsening or Complication of PAH or Initiation of Intravenous Prostanoids, Atrial Septostomy, or Lung Transplantation | Baseline to end of study, approximately 86 months | All randomized set | percentage of participants-Kaplan Meier | NUMBER |
| SECONDARY | Change From Baseline to Week 16 in 6 Minute Walk Test (6MWT) | From baseline to week 16 | All randomized set | m | MEAN |
| SECONDARY | Number of Participants With Improved, No Change, or Worsened World Health Organisation Functional Class From Baseline to Week 16 | From baseline to Week 16 | All randomized set | participants | NUMBER |
| SECONDARY | Time to Death of All Causes From Baseline to End of Study | Baseline to End of Study, approximately 86 months | All randomized set | percentage of participants-Kaplan Meier | NUMBER |
| SECONDARY | Adjusted Percentage Ratio From Baseline in N-terminal Pro-B-type Natriuretic Peptide (NT-pro-BNP) | Baseline to Month 20 | All randomized patients with a baseline and at least one post-baseline value. Assessments considered are those where at least 60% of the patients have a post-baseline value | Adjusted percentage ratio from baseline | GEOMETRIC_MEAN |
| SECONDARY | Change From Baseline to Week 16 in Borg Dyspnea Index | Baseline to Week 16 | All randomized set | units on a scale | MEAN |
| SECONDARY | Change From Baseline to Week 16 in the EuroQol 5 Dimensions (EQ-5D) Questionnaire Calculated Score | From baseline to Week 16 | All randomized set | units on a scale | MEAN |
| SECONDARY | Change From Baseline to Week 16 in the EuroQol 5 Dimensions (EQ-5D) Visual Analogue Scale Score | Baseline to Week 16 | All randomized set | units on a scale | MEAN |
| SECONDARY | Patient Global Self Assessment (PGSA) Status at Week 16 | Week 16 | All randomized set, patients who completed the assessment | participants | NUMBER |
Source ClinicalTrials.gov
Results by group190
Each measurement the trial posted, group by group, in the words and numbers it posted.
| Outcome | Group | Category | Value | Spread | Units |
|---|---|---|---|---|---|
| Time to First Confirmed Morbidity/Mortality Event up to the End of Study | Bosentan | Kaplan-Meier estimate at Month 4 | 96.1 | percentage of participants-Kaplan Meier | |
| Time to First Confirmed Morbidity/Mortality Event up to the End of Study | Placebo | Kaplan-Meier estimate at Month 4 | 90.6 | percentage of participants-Kaplan Meier | |
| Time to First Confirmed Morbidity/Mortality Event up to the End of Study | Bosentan | Kaplan-Meier estimate at Month 8 | 90.5 | percentage of participants-Kaplan Meier | |
| Time to First Confirmed Morbidity/Mortality Event up to the End of Study | Placebo | Kaplan-Meier estimate at Month 8 | 83.0 | percentage of participants-Kaplan Meier | |
| Time to First Confirmed Morbidity/Mortality Event up to the End of Study | Bosentan | Kaplan-Meier estimate at Month 12 | 82.7 | percentage of participants-Kaplan Meier | |
| Time to First Confirmed Morbidity/Mortality Event up to the End of Study | Placebo | Kaplan-Meier estimate at Month 12 | 74.0 | percentage of participants-Kaplan Meier | |
| Time to First Confirmed Morbidity/Mortality Event up to the End of Study | Bosentan | Kaplan-Meier estimate at Month 16 | 74.7 | percentage of participants-Kaplan Meier | |
| Time to First Confirmed Morbidity/Mortality Event up to the End of Study | Placebo | Kaplan-Meier estimate at Month 16 | 71.0 | percentage of participants-Kaplan Meier | |
| Time to First Confirmed Morbidity/Mortality Event up to the End of Study | Bosentan | Kaplan-Meier estimate at Month 20 | 71.8 | percentage of participants-Kaplan Meier | |
| Time to First Confirmed Morbidity/Mortality Event up to the End of Study | Placebo | Kaplan-Meier estimate at Month 20 | 66.1 | percentage of participants-Kaplan Meier |
1 to 10 of 190Source ClinicalTrials.gov
See all 190 results by groupParticipant flow6
How many started, completed or left each group, period by period.
| Period | Milestone | Group | Participants | Units counted |
|---|---|---|---|---|
| Overall Study | STARTED | Bosentan | 159 | |
| Overall Study | STARTED | Placebo | 175 | |
| Overall Study | COMPLETED | Bosentan | 76 | |
| Overall Study | COMPLETED | Placebo | 86 | |
| Overall Study | NOT COMPLETED | Bosentan | 83 | |
| Overall Study | NOT COMPLETED | Placebo | 89 |
Source ClinicalTrials.gov
Adverse events530
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 | OEDEMA PERIPHERAL | General disorders | Bosentan | 30 | 159 | |
| other | OEDEMA PERIPHERAL | General disorders | Placebo | 26 | 174 | |
| other | HEADACHE | Nervous system disorders | Bosentan | 24 | 159 | |
| other | HEADACHE | Nervous system disorders | Placebo | 24 | 174 | |
| other | COUGH | Respiratory, thoracic and mediastinal disorders | Bosentan | 22 | 159 | |
| other | COUGH | Respiratory, thoracic and mediastinal disorders | Placebo | 21 | 174 | |
| other | UPPER RESPIRATORY TRACT INFECTION | Infections and infestations | Bosentan | 21 | 159 | |
| other | UPPER RESPIRATORY TRACT INFECTION | Infections and infestations | Placebo | 29 | 174 | |
| other | DYSPNOEA | Respiratory, thoracic and mediastinal disorders | Bosentan | 21 | 159 | |
| other | DYSPNOEA | Respiratory, thoracic and mediastinal disorders | Placebo | 19 | 174 |
1 to 10 of 530Source ClinicalTrials.gov
See all 530 adverse eventsAdverse event totals6
The totals the trial posted for each group.
| Total | Group | Affected | At risk |
|---|---|---|---|
| Total, all-cause mortality | Bosentan | ||
| Total, all-cause mortality | Placebo | ||
| Total, other adverse events | Bosentan | 135 | 159 |
| Total, other adverse events | Placebo | 147 | 174 |
| Total, serious adverse events | Bosentan | 73 | 159 |
| Total, serious adverse events | Placebo | 102 | 174 |
Source ClinicalTrials.gov
Papers1
The papers the trial lists on ClinicalTrials.gov.
| PMID | Listed as |
|---|---|
| 26113687 | 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 |
|---|
| Bosentan vs Placebo: serious adverse events |
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.
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/NCT00303459
GET https://conductscience.org/api/trials/v1/NCT00303459/results?page=2