Study of Add-on Ambrisentan Therapy to Background Phosphodiesterase Type-5 Inhibitor (PDE5i) Therapy in Pulmonary Arterial Hypertension (ATHENA-1)
NCT ID: NCT00617305
Last Updated: 2012-07-30
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE4
38 participants
INTERVENTIONAL
2008-04-30
2011-07-31
Brief Summary
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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.
Detailed Description
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The secondary objectives of this study are to evaluate the change from baseline in other clinical measures of PAH following the addition of ambrisentan to background PDE-5i therapy in subjects with PAH who have demonstrated a sub-optimal response to PDE-5i monotherapy.
The safety and tolerability of ambrisentan/PDE-5i combination therapy will be evaluated throughout the study. In addition, long-term efficacy will be examined.
Conditions
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Keywords
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
TRIPLE
Study Groups
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Ambrisentan
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; sildenafil or tadalafil).
Ambrisentan
Ambrisentan was administered orally once daily; dose level was 5 mg for the first 4 weeks, followed by 10 mg for the remainder of the study; ambrisentan was supplied as 5-mg and 10-mg tablets.
Sildenafil
Sildenafil was administered at the dose previously established for each subject (20-100 mg) orally three times daily. Sildenafil was supplied as 20-mg tablets, or formulated as sildenafil citrate in 25-, 50-, or 100-mg tablets.
Tadalafil
Tadalafil was administered at the dose previously established for each subject (not to exceed 40 mg per day) orally once daily. Tadalafil was supplied as 20-mg tablets.
Placebo
Patients were assigned placebo at randomization and received at least one dose of placebo plus an approved PDE-5i (sildenafil or tadalafil).
Placebo
Placebo to match ambrisentan was administered orally once daily.
Sildenafil
Sildenafil was administered at the dose previously established for each subject (20-100 mg) orally three times daily. Sildenafil was supplied as 20-mg tablets, or formulated as sildenafil citrate in 25-, 50-, or 100-mg tablets.
Tadalafil
Tadalafil was administered at the dose previously established for each subject (not to exceed 40 mg per day) orally once daily. Tadalafil was supplied as 20-mg tablets.
Interventions
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Ambrisentan
Ambrisentan was administered orally once daily; dose level was 5 mg for the first 4 weeks, followed by 10 mg for the remainder of the study; ambrisentan was supplied as 5-mg and 10-mg tablets.
Placebo
Placebo to match ambrisentan was administered orally once daily.
Sildenafil
Sildenafil was administered at the dose previously established for each subject (20-100 mg) orally three times daily. Sildenafil was supplied as 20-mg tablets, or formulated as sildenafil citrate in 25-, 50-, or 100-mg tablets.
Tadalafil
Tadalafil was administered at the dose previously established for each subject (not to exceed 40 mg per day) orally once daily. Tadalafil was supplied as 20-mg tablets.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* 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.
Exclusion Criteria
* 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.
16 Years
75 Years
ALL
No
Sponsors
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Gilead Sciences
INDUSTRY
Responsible Party
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Locations
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University of South Alabama
Mobile, Alabama, United States
Arizona Pulmonary Specialists
Phoenix, Arizona, United States
West Los Angeles Healthcare Center
Los Angeles, California, United States
Harbor - UCLA
Torrance, California, United States
Cleveland Clinic
Fort Lauderdale, Florida, United States
University of Florida
Gainesville, Florida, United States
Mount Sinai Medical Center
Miami Beach, Florida, United States
Orlando Heart Center
Orlando, Florida, United States
Emory University
Atlanta, Georgia, United States
Atlanta Institute for Medical Research
Decatur, Georgia, United States
University of Iowa
Iowa City, Iowa, United States
University of Maryland
Baltimore, Maryland, United States
BACH Cardiology
Boston, Massachusetts, United States
Brigham & Women's Hospital
Boston, Massachusetts, United States
Wayne State University
Detroit, Michigan, United States
Mayo Clinic
Rochester, Minnesota, United States
Weill Cornell Medical Center
New York, New York, United States
Asheville Cardiology Associates
Asheville, North Carolina, United States
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, United States
The Lindner Clinical Trial Center
Cincinnati, Ohio, United States
University Hospitals of Cleveland
Cleveland, Ohio, United States
Ohio State University
Columbus, Ohio, United States
Altoona Center for Clinical Research
Duncansville, Pennsylvania, United States
Allegheny General Hospital
Pittsburgh, Pennsylvania, United States
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, United States
Rhode Island Hospital
Providence, Rhode Island, United States
UT Southwestern Medical Center
Dallas, Texas, United States
Baylor College of Medicine
Houston, Texas, United States
Scott & White Memorial Hospital
Temple, Texas, United States
Sentara Norfolk General Hospital
Norfolk, Virginia, United States
Countries
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Related Links
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Click here for more information about ambrisentan
Other Identifiers
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GS-US-300-0117
Identifier Type: -
Identifier Source: org_study_id