Trial · NCT01178073
A Study of First-Line Ambrisentan and Tadalafil Combination Therapy in Subjects With Pulmonary Arterial Hypertension (PAH)
NCT01178073, Phase 3, Completed, GlaxoSmithKline; results first posted 2015-04-28
3 sourcestrials-2026-11-12-0.5.0
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ConductScience Library. A Study of First-Line Ambrisentan and Tadalafil Combination Therapy in Subjects With Pulmonary Arterial Hypertension (PAH). Trials, record NCT01178073. Release trials-2026-11-12-0.5.0, 12 Nov 2026. https://conductscience.org/library/trials/NCT01178073
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Trial
As registered on ClinicalTrials.gov, in the graph's capture of the registry.
- Title
- A Study of First-Line Ambrisentan and Tadalafil Combination Therapy in Subjects With Pulmonary Arterial Hypertension (PAH)
- NCT number
- NCT01178073
- Status
- Completed
- Phases
- Phase 3
- Enrollment
- 610 participants, actual
- Lead sponsor
- GlaxoSmithKline
- Conditions
- Hypertension, Pulmonary
- Interventions
- ambrisentan, tadalafil
- First posted
- 2010-08-09
- Last updated
- 2017-09-13
- Results first posted
- 2015-04-28
Source ClinicalTrials.gov
Registered outcomes6
Each outcome the trial registered, primary first, in ClinicalTrials.gov's words.
| List | Outcome | Time frame | Description |
|---|---|---|---|
| Primary | Number of Participants With First Adjudicated Clinical Failure (CF) Event, Death, Hospitalisation for Worsening PAH, Disease Progression, Unsatisfactory Long-term Clinical Response, All Through FAV | From Baseline up to the Final Assessment Visit (FAV) (average of 609 days) | Time to the first adjudicated CF event (death, hospitalization for worsening pulmonary arterial hypertension \[PAH\], disease progression, or unsatisfactory long-term clinical response) after initiating either first-line combination therapy with AMB and TAD or first-line monotherapy with either drug (AMB or TAD) in par. with PAH was assessed. If data was not available for some par. following a loss to follow-up, their event times were treated as censored at their last assessment time for the statistical analyses. FAV occurred approximately 4 weeks after the predicted 105th adjudicated first CF event was reached. Par. who had an FAV, and who had no adjudicated events or whose first adjudicated event occurred after their FAV, were censored at their individual FAV. Modified Intent-to-Treat (mITT) Population: all randomized par. who met the PAH diagnosis and inclusion/exclusion criteria defined in protocol amendment 2 and who also received at least one dose of investigational product (IP). |
| Secondary | Percent Change From Baseline in the N-Terminal Pro-B-Type Natriuretic Peptide at Week 24 | Baseline and Week 24 | N-Terminal Pro-B-Type Natriuretic Peptide (NT-proBNP) is a surrogate marker of heart failure. The data were log-transformed. The geometric mean was calculated (based on the log-transformed data). The geometric mean ratio was calculated as the ratio between the Week 24 value and the Baseline value (based on the log-transformed data) and presented as percent change = 100 \* (geometric mean ratio - 1). The Baseline value is the last value prior to administration of study drug; this may be prior to or on the day of study drug initiation. No imputation was performed for missing data. The secondary endpoints were analyzed according to a pre-specified hierarchical testing procedure. |
| Secondary | Percentage of Participants With a Satisfactory Clinical Response at Week 24 | Baseline and Week 24 | A satisfactory clinical response at Week 24 is defined as a participant who meets all of the following criteria: 10% improvement in 6MWD compared with Baseline; improvement to or maintenance of World Health Organization (WHO) class I or II symptoms; no events of clinical worsening prior to or at the Week 24 visit. Clinical worsening events included: death, hospitalization for pulmonary arterial hypertension (PAH), and disease progression. Participants without an event of clinical worsening prior to or at the Week 24 visit who did not have a 6MWD value or a WHO functional class value at Week 24 were excluded from the analysis. |
| Secondary | Change From Baseline in the 6 Minute Walk Distance Test at Week 24 | Baseline and Week 24 | The 6-minute walk distance (6MWD) test measures the distance that a participant can walk in a period of 6 minutes. Change from Baseline was calculated as the Week 24 value minus the Baseline value. The analysis was performed based on last observation carried forward data, except in the case of an adjudicated clinical failure event of death or hospitalization preceding the missing data observation. In this case, the missing observation was assigned the worst-rank score relative to those actually observed and was assigned a rank reflecting the relative order of the actual event times. Baseline 6MWD comprised of an average of the last two consecutive measurements prior to randomization that varied by no greater than 10%. If only one measurement was available, that measurement was used. If no two consecutive measures vary by no greater than 10% then Baseline was based on the last two consecutive measures for a participant. |
| Secondary | Change From Baseline in the World Health Organization Functional Class at Week 24 | Baseline and Week 24 | The WHO Functional Class (FC) indicates the severity of PAH and is an adaptation of the New York Heart Association classification. It was assessed by the investigator. There are four grades for WHO FC based on severity of symptoms (Class I = none, Class IV = most severe). Baseline WHO FC is the latest assessment prior to dosing (i.e., at Randomization or Screening). Change from Baseline at Week 24 was calculated as the Week 24 value minus the Baseline value. The analysis was performed based on the last observation carried forward data, except in the case of an adjudicated clinical failure event of death or hospitalization preceding the missing data observation. In this case, the missing observations was assigned the worst-rank score relative to those actually observed and was assigned rank reflecting the relative order of the actual event times. |
| Secondary | Change From Baseline in Borg Dyspnea Index at Week 24 | Baseline (BL) and Week 24 | Borg Dyspnea Index (BDI) indicates the degree of breathlessness after completion of the 6 minute walk test. The BDI was calculated by using the Borg category (C) ratio (R) CR10 scale which starts at 0 (nothing at all) and has no upper limit (extremely strong). Change from BL was calculated as the Week 24 values minus the BL value. The BDI scale was assessed by each participant. The BL BDI score is the average of the two BDI values obtained following the two 6MWD tests used in determining the BL 6MWD. A negative change from BL in the BDI score represented an improvement for the participant. The analysis was performed based on the last observation carried forward data, except in the case of an adjudicated clinical failure event of death or hospitalization preceding the missing data observation. In this case, the missing observation was assigned the worst-rank score relative to those actually observed and was assigned rank reflecting the relative order of the actual event times. |
Source ClinicalTrials.gov
Outcomes6
Each outcome the trial posted results for, in ClinicalTrials.gov's words.
| Type | Outcome | Time frame | Population | Units | Measured as |
|---|---|---|---|---|---|
| PRIMARY | Number of Participants With First Adjudicated Clinical Failure (CF) Event, Death, Hospitalisation for Worsening PAH, Disease Progression, Unsatisfactory Long-term Clinical Response, All Through FAV | From Baseline up to the Final Assessment Visit (FAV) (average of 609 days) | mITT Population | Participants | NUMBER |
| SECONDARY | Percent Change From Baseline in the N-Terminal Pro-B-Type Natriuretic Peptide at Week 24 | Baseline and Week 24 | mITT Population. Only participants with data available at the specified time points were analyzed. | Percent change | MEAN |
| SECONDARY | Percentage of Participants With a Satisfactory Clinical Response at Week 24 | Baseline and Week 24 | mITT Population. Only those participants who had a Yes/No response were analyzed. | Percentage of participants | NUMBER |
| SECONDARY | Change From Baseline in the 6 Minute Walk Distance Test at Week 24 | Baseline and Week 24 | mITT Population. Only participants with Baseline data were analyzed. | Meters | MEDIAN |
| SECONDARY | Change From Baseline in the World Health Organization Functional Class at Week 24 | Baseline and Week 24 | mITT Population. Only participants with Baseline data were analyzed. | Scores on a scale | MEDIAN |
| SECONDARY | Change From Baseline in Borg Dyspnea Index at Week 24 | Baseline (BL) and Week 24 | mITT Population. Only participants with Baseline data were analyzed. | Scores on a scale | MEDIAN |
Source ClinicalTrials.gov
Results by group40
Each measurement the trial posted, group by group, in the words and numbers it posted.
| Outcome | Group | Category | Value | Spread | Units |
|---|---|---|---|---|---|
| Number of Participants With First Adjudicated Clinical Failure (CF) Event, Death, Hospitalisation for Worsening PAH, Disease Progression, Unsatisfactory Long-term Clinical Response, All Through FAV | Combination Therapy: Ambrisentan + Tadalafil | First adjudicated clinical failure event | 46 | Participants | |
| Number of Participants With First Adjudicated Clinical Failure (CF) Event, Death, Hospitalisation for Worsening PAH, Disease Progression, Unsatisfactory Long-term Clinical Response, All Through FAV | Monotherapy Pooled: Ambrisentan or Tadalafil | First adjudicated clinical failure event | 77 | Participants | |
| Number of Participants With First Adjudicated Clinical Failure (CF) Event, Death, Hospitalisation for Worsening PAH, Disease Progression, Unsatisfactory Long-term Clinical Response, All Through FAV | Ambrisentan Monotherapy | First adjudicated clinical failure event | 43 | Participants | |
| Number of Participants With First Adjudicated Clinical Failure (CF) Event, Death, Hospitalisation for Worsening PAH, Disease Progression, Unsatisfactory Long-term Clinical Response, All Through FAV | Tadalafil Monotherapy | First adjudicated clinical failure event | 34 | Participants | |
| Number of Participants With First Adjudicated Clinical Failure (CF) Event, Death, Hospitalisation for Worsening PAH, Disease Progression, Unsatisfactory Long-term Clinical Response, All Through FAV | Combination Therapy: Ambrisentan + Tadalafil | Death (all-cause) | 9 | Participants | |
| Number of Participants With First Adjudicated Clinical Failure (CF) Event, Death, Hospitalisation for Worsening PAH, Disease Progression, Unsatisfactory Long-term Clinical Response, All Through FAV | Monotherapy Pooled: Ambrisentan or Tadalafil | Death (all-cause) | 8 | Participants | |
| Number of Participants With First Adjudicated Clinical Failure (CF) Event, Death, Hospitalisation for Worsening PAH, Disease Progression, Unsatisfactory Long-term Clinical Response, All Through FAV | Ambrisentan Monotherapy | Death (all-cause) | 2 | Participants | |
| Number of Participants With First Adjudicated Clinical Failure (CF) Event, Death, Hospitalisation for Worsening PAH, Disease Progression, Unsatisfactory Long-term Clinical Response, All Through FAV | Tadalafil Monotherapy | Death (all-cause) | 6 | Participants | |
| Number of Participants With First Adjudicated Clinical Failure (CF) Event, Death, Hospitalisation for Worsening PAH, Disease Progression, Unsatisfactory Long-term Clinical Response, All Through FAV | Combination Therapy: Ambrisentan + Tadalafil | Hospitalization for worsening PAH | 10 | Participants | |
| Number of Participants With First Adjudicated Clinical Failure (CF) Event, Death, Hospitalisation for Worsening PAH, Disease Progression, Unsatisfactory Long-term Clinical Response, All Through FAV | Monotherapy Pooled: Ambrisentan or Tadalafil | Hospitalization for worsening PAH | 30 | Participants |
1 to 10 of 40Source ClinicalTrials.gov
See all 40 results by groupParticipant flow9
How many started, completed or left each group, period by period.
| Period | Milestone | Group | Participants | Units counted |
|---|---|---|---|---|
| Overall Study | STARTED | Combination Therapy: Ambrisentan + Tadalafil | 302 | |
| Overall Study | STARTED | Ambrisentan Monotherapy | 152 | |
| Overall Study | STARTED | Tadalafil Monotherapy | 151 | |
| Overall Study | COMPLETED | Combination Therapy: Ambrisentan + Tadalafil | 240 | |
| Overall Study | COMPLETED | Ambrisentan Monotherapy | 108 | |
| Overall Study | COMPLETED | Tadalafil Monotherapy | 105 | |
| Overall Study | NOT COMPLETED | Combination Therapy: Ambrisentan + Tadalafil | 62 | |
| Overall Study | NOT COMPLETED | Ambrisentan Monotherapy | 44 | |
| Overall Study | NOT COMPLETED | Tadalafil Monotherapy | 46 |
Source ClinicalTrials.gov
Adverse events939
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 | Combination Therapy: Ambrisentan + Tadalafil | 133 | 302 | |
| other | Oedema peripheral | General disorders | Ambrisentan Monotherapy | 60 | 152 | |
| other | Oedema peripheral | General disorders | Tadalafil Monotherapy | 44 | 151 | |
| other | Fatigue | General disorders | Combination Therapy: Ambrisentan + Tadalafil | 35 | 302 | |
| other | Fatigue | General disorders | Ambrisentan Monotherapy | 22 | 152 | |
| other | Fatigue | General disorders | Tadalafil Monotherapy | 20 | 151 | |
| other | Non-cardiac chest pain | General disorders | Combination Therapy: Ambrisentan + Tadalafil | 26 | 302 | |
| other | Non-cardiac chest pain | General disorders | Ambrisentan Monotherapy | 14 | 152 | |
| other | Non-cardiac chest pain | General disorders | Tadalafil Monotherapy | 9 | 151 | |
| other | Pyrexia | General disorders | Combination Therapy: Ambrisentan + Tadalafil | 17 | 302 |
1 to 10 of 939Source ClinicalTrials.gov
See all 939 adverse eventsAdverse event totals9
The totals the trial posted for each group.
| Total | Group | Affected | At risk |
|---|---|---|---|
| Total, all-cause mortality | Combination Therapy: Ambrisentan + Tadalafil | ||
| Total, all-cause mortality | Ambrisentan Monotherapy | ||
| Total, all-cause mortality | Tadalafil Monotherapy | ||
| Total, other adverse events | Combination Therapy: Ambrisentan + Tadalafil | 279 | 302 |
| Total, other adverse events | Ambrisentan Monotherapy | 140 | 152 |
| Total, other adverse events | Tadalafil Monotherapy | 135 | 151 |
| Total, serious adverse events | Combination Therapy: Ambrisentan + Tadalafil | 124 | 302 |
| Total, serious adverse events | Ambrisentan Monotherapy | 63 | 152 |
| Total, serious adverse events | Tadalafil Monotherapy | 68 | 151 |
Source ClinicalTrials.gov
Papers5
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.
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/NCT01178073
GET https://conductscience.org/api/trials/v1/NCT01178073/results?page=2