Clinical trial NCT00091598: ARIES - Ambrisentan in Patients With Moderate to Severe Pulmonary Arterial Hypertension (PAH)
Official title: ARIES 1 and ARIES 2: Ambrisentan in PAH - A Phase III, Randomized, Double-blind, Placebo-controlled, Multicenter, Efficacy Study of Ambrisentan in Subjects With Pulmonary Arterial Hypertension
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pulmonary Hypertension
Keywords: Pulmonary Arterial Hypertension
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2004-09-14
Enrollment: 372
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective is to determine the effect of ambrisentan on exercise capacity in subjects with PAH.

Detailed description: ARIES-1 in North America and Australia

ARIES-2 in Western and Eastern Europe, South America and Israel

Subjects in these randomized studies will receive one of two doses of ambrisentan or placebo. Inclusion is not based on a specified WHO functional classification. Rather, subjects with WHO Class I-IV symptoms are eligible if their 6-minute walk distance is 150-450 meters and they meet the study-specified hemodynamic criteria. Subjects with anorexigen or HIV infection related PAH are eligible but subjects with congenital heart disease and pediatric subjects are excluded. The study requires a historical cardiac catheterization and other diagnostic procedures.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of idiopathic PAH (formally known as PPH), or PAH associated with collagen vascular disease, anorexigen use, or HIV infection;
* Historical cardiac catheterization with the following hemodynamic criteria:

Mean pulmonary artery pressure greater than or equal to 25 mmHg; Pulmonary vascular resistance greater than 3 mmHg/L/min; Pulmonary capillary wedge pressure or left ventricular end diastolic pressure less than 15 mmHg;

* 6-minute walk distance of at least 150 meters, but no more than 450 meters;
* Total lung capacity greater than or equal to 70% and FEV1 greater than or equal to 65% of predicted normal;

Exclusion Criteria:

* Portopulmonary hypertension;
* Subjects with PAH due to or associated with coronary artery disease, left heart disease, interstitial lung disease, chronic obstructive pulmonary disease, veno-occlusive disease, chronic thromboembolic disease, or sleep apnea;
* Bosentan (Tracleer®), sildenafil (Viagra®), or chronic prostanoid therapy within 4 weeks of screening;
* Serum ALT or AST lab value that is greater than 1.5 times the upper limit of normal;
* Contraindication to treatment with an endothelin receptor antagonist;
* Subject with cardiovascular, hepatic, renal, hematologic, gastrointestinal, immunologic, endocrine, metabolic, or central nervous system disease that may adversely affect the safety of the subject;
* Participation in a clinical study involving another investigational drug within 4 weeks of screening.

Primary outcomes:
measure: Change from baseline at Week 12 of six minute walk distance
Secondary outcomes:
measure: Change from baseline at Week 12 of:
measure: Borg Dsypnea Index
measure: WHO Functional Classification
measure: SF-36
measure: Time to Clinical Worsening
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Pulmonary Associates, PA
state: Arizona
city: Phoenix
country: United States
facility: Arizona Pulmonary Specialists
state: Arizona
city: Los Angeles
country: United States
facility: Brentwood Biomedical Research Institute
state: California
city: Sacramento
country: United States
facility: University of California-Davis
state: California
city: San Diego
country: United States
facility: University of California San Diego Medical Center
state: California
city: Torrance
country: United States
facility: Los Angeles County Harbor-UCLA Medical Center
state: California
city: Denver
country: United States
facility: University of Colorado Health Sciences Center
state: Colorado
city: Westminster
country: United States
facility: Myogen
state: Colorado
city: Farmington
country: United States
facility: University of Connecticut Health Center
state: Connecticut
city: Miami
country: United States
facility: Mt. Sinai Medical Center
state: Florida
city: Atlanta
country: United States
facility: Emory University Hospital
state: Georgia
city: Augusta
country: United States
facility: Medical College of Georgia
state: Georgia
city: Chicago
country: United States
facility: Loyola University Medical Center
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: New Orleans
country: United States
facility: Ochsner Clinic
state: Louisiana
city: Portland
country: United States
facility: Maine Medical Center
state: Maine
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Boston
country: United States
facility: Tufts New England Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Medical Center
state: Michigan
city: Detroit
country: United States
facility: Wayne State University
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: St. Louis
country: United States
facility: Washington University
state: Missouri
city: Manhasset
country: United States
facility: Northshore University/Long Island Jewish Hospital
state: New York
city: Mineola
country: United States
facility: Winthrop University Hospital
state: New York
city: New York City
country: United States
facility: Mt. Sinai Medical Center
state: New York
city: New York
country: United States
facility: New York Presbyterian Hospital
state: New York
city: Syracuse
country: United States
facility: Cardiology PC
state: New York
city: Cincinnati
country: United States
facility: Lindner Clinical Trial Center
state: Ohio
city: Cleveland
country: United States
facility: University Hospitals of Cleveland
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Portland
country: United States
facility: Oregon Health Sciences University
state: Oregon
city: Philadelphia
country: United States
facility: University of Pennsylvania Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Dallas
country: United States
facility: St. Paul Hospital
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: San Antonio
country: United States
facility: University of Texas - San Antonio
state: Texas
city: Temple
country: United States
facility: Scott & White Hospital
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia Health System
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Milwaukee
country: United States
facility: Heart Care Associates
state: Wisconsin
city: Sydney
country: Australia
facility: St. Vincent's Hospital
state: New South Wales
city: Montreal
country: Canada
facility: Jewish General Hospital
state: Quebec
Study officials:
affiliation: University of California San Diego, San Diego School of Medicine
name: Lewis J. Rubin, MD
role: STUDY_CHAIR
References:
citation: Galie N, Olschewski H, Oudiz RJ, Torres F, Frost A, Ghofrani HA, Badesch DB, McGoon MD, McLaughlin VV, Roecker EB, Gerber MJ, Dufton C, Wiens BL, Rubin LJ; Ambrisentan in Pulmonary Arterial Hypertension, Randomized, Double-Blind, Placebo-Controlled, Multicenter, Efficacy Studies (ARIES) Group. Ambrisentan for the treatment of pulmonary arterial hypertension: results of the ambrisentan in pulmonary arterial hypertension, randomized, double-blind, placebo-controlled, multicenter, efficacy (ARIES) study 1 and 2. Circulation. 2008 Jun 10;117(23):3010-9. doi: 10.1161/CIRCULATIONAHA.107.742510. Epub 2008 May 27.