Study of Add-on Ambrisentan Therapy to Background Phosphodiesterase Type-5 Inhibitor (PDE5i) Therapy in Pulmonary Arterial Hypertension (ATHENA-1) (ATHENA-1)

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Patients were enrolled in 16 study sites in the US. The first patient was screened on 09 April 2008, and the last patient was enrolled on 28 July 2010. The last patient observation was on 25 July 2011. Originally a double-blind, placebo-controlled study, it was changed to open label on 12 June 2009 due to slow enrollment.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
65 patients were screened; 8 were randomized (3 to ambrisentan and 5 to placebo) prior to study conversion to open label. The remaining patients were assigned to ambrisentan treatment.

Reporting Groups

	Description
Ambrisentan Only	Patients were assigned ambrisentan at open-label enrollment or randomization, and received at least one dose of ambrisentan plus an approved phosphodiesterase type-5 (PDE-5) inhibitor (PDE-5i)
Placebo/Ambrisentan	Patients were assigned placebo at randomization and received at least one dose of placebo plus an approved PDE-5i; patients also received at least one dose of open-label ambrisentan plus an approved PDE-5i
Placebo Only	Patients were assigned placebo at randomization and received at least one dose of placebo plus an approved PDE-5i

Participant Flow:   Overall Study

	Ambrisentan Only	Placebo/Ambrisentan	Placebo Only
STARTED	33	4	1
Completed 24-week Primary Analysis	31	4	0
COMPLETED	25	4	0
NOT COMPLETED	8	0	1
Adverse Event	4	0	0
Death	1	0	0
Physician Decision	1	0	0
Protocol Violation	1	0	1
Withdrawal by Subject	1	0	0

1.  Primary:

Change From Baseline in Pulmonary Vascular Resistance (PVR), Last Observation Carried Forward (LOCF)   [ Time Frame: Baseline to Week 24 ]

2.  Secondary:

Change From Baseline in Mean Pulmonary Artery Pressure (mPAP) (LOCF)   [ Time Frame: Baseline to Week 24 ]

3.  Secondary:

Change From Baseline in Mean Right Atrial Pressure (mRAP) (LOCF)   [ Time Frame: Baseline to Week 24 ]

4.  Secondary:

Change From Baseline in Cardiac Output (LOCF)   [ Time Frame: Baseline to Week 24 ]

5.  Secondary:

Change From Baseline in Six Minute Walk Distance (6MWD) Measured at Weeks 4, 12, 24, 36 and 48 (LOCF)   [ Time Frame: Baseline to Week 48 ]

6.  Secondary:

Change in Dyspnea Index Measured at Weeks 4, 12, 24, 36 and 48 (LOCF)   [ Time Frame: Baseline to Week 48 ]

7.  Secondary:

Change From Baseline in the Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) Quality of Life (QOL) Survey Overall Score Measured at Weeks 12, 24, 36 and 48 (LOCF)   [ Time Frame: Baseline to Week 48 ]

8.  Secondary:

Change From Baseline in World Health Organization (WHO) Functional Class (LOCF) Measured at Weeks 4, 12, 24, 36 and 48.   [ Time Frame: Baseline to Week 48 ]

9.  Secondary:

Change From Baseline in Log-transformed N-terminal Pro-B-type Natriuretic Peptide (NT-proBNP) Measured at Weeks 4, 12, 24, 36 and 48 (LOCF)   [ Time Frame: Baseline to Week 48 ]

10.  Secondary:

Time to Clinical Worsening of PAH, Evaluated at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and After Week 48   [ Time Frame: Baseline to Week 48+ ]

11.  Secondary:

Overall Survival, Evaluated at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and After Week 48   [ Time Frame: Baseline to Week 48+ ]

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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