Phase 4
Completed N=38
Study of Add-on Ambrisentan Therapy to Background Phosphodiesterase Type-5 Inhibitor (PDE5i) Therapy in Pulmonary Arterial Hypertension (ATHENA-1)
Source: ClinicalTrials.gov NCT00617305 ↗Enrolled (actual)
38
Serious AEs
29.3%
Results posted
Jul 2012
Primary outcomePrimary: Change From Baseline in Pulmonary Vascular Resistance (PVR), Last Observation Carried Forward (LOCF) — 761.2; 731.6; 758.0; 703.6 dynes sec/cm^5
Summary
To evaluate the change from baseline in pulmonary vascular resistance (PVR), and other hemodynamic parameters, following the addition of ambrisentan to background phosphodiesterase type-5 inhibitor (PDE-5i) therapy in subjects with pulmonary arterial hypertension (PAH) who have demonstrated a sub-optimal response to PDE-5i monotherapy.
The study was originally designed as a 2-arm, double-blind, randomized study in which patients received ambrisentan or placebo for 24 weeks, and then received ambrisentan blinded to dose for 24 weeks. With Protocol Amendment 2 (12 June, 2009), the study was switched to single-arm, open-label treatment, and all patients remaining in the placebo arm were switched to open-label ambrisentan treatment. Patients who enrolled after Amendment 2 all received open-label ambrisentan.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change From Baseline in Pulmonary Vascular Resistance (PVR), Last Observation Carried Forward (LOCF) |
761.2; 731.6; 758.0; 703.6; 518.8; 439.8 | — |
| SECONDARY Change From Baseline in Mean Pulmonary Artery Pressure (mPAP) (LOCF) |
49.9; 54.5; 50.4; 52.8; 44.4; 38.8 | — |
| SECONDARY Change From Baseline in Mean Right Atrial Pressure (mRAP) (LOCF) |
8.5; 10.3; 8.7; 11.1; 8.4; 6.3 | — |
| SECONDARY Change From Baseline in Cardiac Output (LOCF) |
4.4; 4.8; 4.4; 4.8; 5.2; 5.2 | — |
| SECONDARY Change From Baseline in Six Minute Walk Distance (6MWD) Measured at Weeks 4, 12, 24, 36 and 48 (LOCF) |
361.9; 433.3; 335.0; 369.6; 413.6; 376.5 | — |
| SECONDARY Change in Dyspnea Index Measured at Weeks 4, 12, 24, 36 and 48 (LOCF) |
3.7; 2.5; 3.0; 3.6; 2.6; 3.2 | — |
| 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) |
8.2; 4.3; 4.0; 7.7; 4.2; 6.8 | — |
| SECONDARY Change From Baseline in World Health Organization (WHO) Functional Class (LOCF) Measured at Weeks 4, 12, 24, 36 and 48. |
3; 0; 1; 3; 1; 29 | — |
| 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) |
6.1; 6.7; 0.0; 6.2; 6.7; 5.7 | — |
| 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 |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Overall Survival, Evaluated at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and After Week 48 |
0; 0; 0; 0; 0; 0 | — |
Eligibility Criteria
Selected Inclusion Criteria
- Must be between 16 and 75 years of age;
- Must weigh at least 40 kg;
- Have a current diagnosis of idiopathic PAH, familial PAH, or PAH that is primarily due to connective tissue disease, congenital heart defects, drug or toxin use, or human immunodeficiency virus (HIV);
- Have WHO functional class III symptoms;
- Be receiving sildenafil or tadalafil monotherapy for the treatment of PAH for at least the past 12 weeks and at a stable dose for at least 8 consecutive weeks;
- Meet all of the following hemodynamic criteria by means of a right heart catheterization: mPAP of at least 25 mmHg; PVR of at least 400 dyne*sec/cm5; pulmonary capillary wedge pressure (PCWP) or left ventricular end diastolic pressure (LVEDP) of not more than 15 mmHg;
- Meet all of the following pulmonary function test criteria no more than 12 weeks before the screening visit: total lung capacity at least 60% of predicted normal and forced expiratory volume in 1 second of at least 65% of predicted normal;
- Able to walk at least 150 meters during the screening 6-minute walk test (6MWT);
- If receiving calcium channel blockers or 5-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (i.e., statins) must be on stable therapy for at least 4 weeks;
- If diagnosed with HIV, must have stable disease status.
Selected Exclusion Criteria:
- Have a current pulmonary hypertension diagnosis other than idiopathic PAH, familial PAH, or PAH that is primarily due to connective tissue disease, congenital heart defects, drug or toxin use, or HIV;
- Have left ventricular ejection fraction (LVEF) ≤40% or clinically significant ischemic, valvular, or constrictive heart disease;
- Have received chronic prostanoid or endothelin receptor antagonist (ERA) therapy (eg, bosentan, sitaxsentan) within the past 12 weeks;
- Have discontinued ERA treatment for any adverse reaction other than those associated with liver function test abnormalities;
- Have received IV inotropes within 2 weeks;
- Have a serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) value that is greater than 2.0x the upper limit of normal.
Data sourced from ClinicalTrials.gov (NCT00617305). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.