ARIES - Ambrisentan in Patients With Moderate to Severe Pulmonary Arterial Hypertension (PAH)

Pulmonary Hypertension Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00091598
• Other study ID #: ARIES
• Status: Completed
• Phase: Phase 3
• First received: September 10, 2004
• Last updated: March 4, 2010
• Start date: January 2004
• Est. completion date: February 2006

Study information

• Verified date: March 2010
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 372
• Est. completion date: February 2006
• Est. primary completion date: February 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hypertension
• Hypertension, Pulmonary
• Pulmonary Hypertension

Intervention

Drug:
• Ambrisentan

Locations

Country	Name	City	State
Australia	St. Vincent's Hospital	Sydney	New South Wales
Canada	Jewish General Hospital	Montreal	Quebec
United States	University of Michigan Medical Center	Ann Arbor	Michigan
United States	Emory University Hospital	Atlanta	Georgia
United States	Medical College of Georgia	Augusta	Georgia
United States	Johns Hopkins University	Baltimore	Maryland
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Tufts New England Medical Center	Boston	Massachusetts
United States	University of Virginia Health System	Charlottesville	Virginia
United States	Loyola University Medical Center	Chicago	Illinois
United States	Lindner Clinical Trial Center	Cincinnati	Ohio
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	University Hospitals of Cleveland	Cleveland	Ohio
United States	St. Paul Hospital	Dallas	Texas
United States	University of Colorado Health Sciences Center	Denver	Colorado
United States	Wayne State University	Detroit	Michigan
United States	University of Connecticut Health Center	Farmington	Connecticut
United States	Baylor College of Medicine	Houston	Texas
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	Brentwood Biomedical Research Institute	Los Angeles	California
United States	Northshore University/Long Island Jewish Hospital	Manhasset	New York
United States	Mt. Sinai Medical Center	Miami	Florida
United States	Heart Care Associates	Milwaukee	Wisconsin
United States	Winthrop University Hospital	Mineola	New York
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Ochsner Clinic	New Orleans	Louisiana
United States	New York Presbyterian Hospital	New York	New York
United States	Mt. Sinai Medical Center	New York City	New York
United States	University of Pennsylvania Hospital	Philadelphia	Pennsylvania
United States	Arizona Pulmonary Specialists	Phoenix	Arizona
United States	Pulmonary Associates, PA	Phoenix	Arizona
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	Maine Medical Center	Portland	Maine
United States	Oregon Health Sciences University	Portland	Oregon
United States	Rhode Island Hospital	Providence	Rhode Island
United States	Virginia Commonwealth University	Richmond	Virginia
United States	Mayo Clinic	Rochester	Minnesota
United States	University of California-Davis	Sacramento	California
United States	University of Texas - San Antonio	San Antonio	Texas
United States	University of California San Diego Medical Center	San Diego	California
United States	Washington University	St. Louis	Missouri
United States	Cardiology PC	Syracuse	New York
United States	Scott & White Hospital	Temple	Texas
United States	Los Angeles County Harbor-UCLA Medical Center	Torrance	California
United States	Myogen	Westminster	Colorado

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  Australia,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline at Week 12 of six minute walk distance
Secondary	Change from baseline at Week 12 of:
Secondary	Borg Dsypnea Index
Secondary	WHO Functional Classification
Secondary	SF-36
Secondary	Time to Clinical Worsening

External Links

•   Pulmonary Hypertension Association