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

• Register: ClinicalTrials.gov
• Last refreshed on: 19 October 2017
• Main ID: NCT00617305
• Date of registration: 06/02/2008
• Prospective Registration: Yes
• Primary sponsor: Gilead Sciences
• Public title: Study of Add-on Ambrisentan Therapy to Background Phosphodiesterase Type-5 Inhibitor (PDE5i) Therapy in Pulmonary Arterial Hypertension (ATHENA-1) ATHENA-1
• Scientific title: An Open-label, Multicenter Study of Ambrisentan and a Phosphodiesterase Type-5 Inhibitor Combination Therapy in Subjects With Pulmonary Arterial Hypertension Who Have Demonstrated a Sub-Optimal Response to a Phosphodiesterase Type-5 Inhibitor
• Date of first enrolment: April 2008
• Target sample size: 38
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT00617305
• Study type: Interventional
• Phase: Phase 4

Countries of recruitment

United States

Key inclusion & exclusion 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.



Age minimum: 16 Years
Age maximum: 75 Years
Gender: All

Health Condition(s) or Problem(s) studied

Pulmonary Arterial Hypertension

Intervention(s)

Drug: Ambrisentan

Drug: Sildenafil

Drug: Tadalafil

Drug: Placebo

Primary Outcome(s)

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

Secondary Outcome(s)

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]

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+]

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

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]

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]

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+]

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]

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

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

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

Secondary ID(s)

GS-US-300-0117

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 30/07/2012
• URL: https://clinicaltrials.gov/ct2/show/results/NCT00617305