ARTEMIS-PH - Study of Ambrisentan in Subjects With Pulmonary Hypertension Associated With Idiopathic Pulmonary Fibrosis
- Conditions
- Idiopathic Pulmonary FibrosisPulmonary Hypertension
- Interventions
- Drug: Placebo
- Registration Number
- NCT00879229
- Lead Sponsor
- Gilead Sciences
- Brief Summary
Ambrisentan is an endothelin receptor antagonist used for the treatment of pulmonary hypertension (PH). Based on research suggesting a role for endothelin-1 in the pathogenesis of idiopathic pulmonary fibrosis (IPF) and the poor prognosis for patients with IPF who are also diagnosed with PH, this study was designed to evaluate the effectiveness and safety of ambrisentan in that patient population.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 40
- Weight ≥ 40 kg at screening
- Diagnosis of IPF based on modified American Thoracic Society-European Respiratory Society guidelines
- Diagnosis of PH based on the following hemodynamic requirements: mean pulmonary artery pressure (mPAP ≥ 25 mm Hg; pulmonary vascular resistance > 240 dyne.sec/cm^5; pulmonary capillary wedge pressure or left ventricular end-diastolic pressure ≤ 15 mm Hg
- Forced vital capacity (FVC) ≥ 40%
- Able to walk at least 50 meters during two 6-minute walk tests
- If receiving calcium channel blockers, low-dose oral corticosteroids, immunosuppressive, cytoxic, or antifibrotic drugs dose must have been stable.
Selected
- Diagnosis of PH primarily due to an etiology other than IPF
- Surgical lung biopsy diagnosis other than Usual Interstitial Pneumonia
- Other known cause of interstitial lung disease
- Evidence of significant obstructive lung disease
- Recent hospitalization for an acute exacerbation of IPF
- Recent active pulmonary or upper respiratory tract infection
- Left ventricular ejection fraction < 40%
- Serum creatinine ≥ 2.5 mg/dL
- Required hemodialysis, peritoneal dialysis, or hemofiltration
- Female subject who was pregnant or breastfeeding
- Recent treatment for PH with an endothelin receptor antagonist (ERA), phosphodiesterase type 5 inhibitor, or prostacyclin derivative
- Recent treatment with high dose oral corticosteroids
- Recent treatment (within 4 weeks prior to screening) with imatinib mesylate (Gleevec)
- Alanine aminotransferase or aspartate aminotransferase lab value that was greater than 1.5 x the upper limit of the normal range
- Discontinued other ERA treatment for any adverse reaction other than those associated with liver function test abnormalities
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Ambrisentan Ambrisentan Participants were randomized to receive ambrisentan treatment at an initial dose of 5 mg for 4 weeks, followed by ambrisentan at the target dose of 10 mg for an additional 52 weeks Placebo Placebo Participants were randomized to receive placebo to match ambrisentan for 48 weeks, then transition to ambrisentan treatment at the initial dose of 5 mg for 4 weeks, followed by ambrisentan at the target dose of 10 mg for an additional 4 weeks. Placebo Ambrisentan Participants were randomized to receive placebo to match ambrisentan for 48 weeks, then transition to ambrisentan treatment at the initial dose of 5 mg for 4 weeks, followed by ambrisentan at the target dose of 10 mg for an additional 4 weeks.
- Primary Outcome Measures
Name Time Method Change From Baseline in Six-minute Walk Distance (6MWD). Baseline to Week 16 The change from baseline in 6MWD at Week 16 (end of blinded treatment) was evaluated.
- Secondary Outcome Measures
Name Time Method Long-term Survival Week 48 Long-term survival was assessed as a Kaplan-Meier (KM) estimate of the percent probability of survival, with censoring at Week 48.
Transition Dyspnea Index (TDI) Baseline to Week 16 The change in TDI at Week 16 (end of blinded treatment) was evaluated. TDI measures the change from the baseline characteristic "Baseline Dyspnea Index." The TDI range is -9 to +9 (worst to best; 0 = no change).
Change From Baseline in WHO Functional Class Baseline to Week 16 WHO functional class rates severity of pulmonary hypertension, with 4 categories on a scale of 1 to 4 with the worst category being 4. Change is represented as an increase ("+1: Improved"), decrease ("-1: Deteriorated"), or no change ("0: No change") on the scale.
Change From Baseline in Forced Vital Capacity (FVC) Percent Predicted Baseline to Week 16 FVC is a pulmonary function test, and is defined as the volume of air that can forcibly be blown out after taking a full breath. FVC% predicted is defined as FVC% of the patient divided by the average FVC% in the population for any person of similar age, sex and body composition.
Change From Baseline in N-terminal Pro-B-type Natriuretic Peptide (NT-proBNP) Baseline to Week 16 Assessment of the the level of the amino acid fragment NT-proBNP is used to establish prognosis in cardiovascular disease.
Change From Baseline in the Borg Dyspnea Index (BORG) Immediately Following Exercise Baseline to Week 16 Borg Dyspnea Index is a measure of perceived shortness of breath: 0 units on a scale (none) to 10 units on a scale (maximum breathlessness).
Hemoglobin-corrected Diffusing Capacity for Carbon Monoxide (DLCO) Percent Predicted Baseline to Week 16 DLCO is a pulmonary function test, and measures the partial pressure difference between inspired and expired carbon monoxide. DLCO% predicted is defined as DLCO% of the patient divided by the average DLCO% in the population for any person of similar age, sex and body composition.
Change in Quality of Life (QOL) Score as Assessed by the Short-Form 36® (SF-36) Baseline to Week 16 Each SF-36 score is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. An increase in score indicates an improvement in health state.
Change in QOL Score as Assessed by the St. George's Respiratory Questionnaire (SRGQ) Baseline to Week 16 The SRGQ is designed to measure impact on overall health, daily life, and perceived well-being in patients with obstructive airways disease. Patients respond to questions about symptoms (frequency \& severity) and impact components (social functioning and psychological disturbances resulting from airways disease). Scores range from 0 to 100, with higher scores indicating more limitations.
Trial Locations
- Locations (85)
Mayo Clinic Arizona
🇺🇸Scottsdale, Arizona, United States
Medizinische Universität Graz
🇦🇹Graz, Austria
Universitatsklinikum Innsbruck
🇦🇹Innsbruck, Austria
Johns Hopkins University School of Medicine
🇺🇸Baltimore, Maryland, United States
David Geffen School of Medicine UCLA
🇺🇸Los Angeles, California, United States
Bay Area Chest Physicians
🇺🇸Clearwater, Florida, United States
Albany Medical Center
🇺🇸Albany, New York, United States
University Hospitals of Cleveland Case Western
🇺🇸Cleveland, Ohio, United States
Hospital of the University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
University of Pittsburgh Cancer Institute
🇺🇸Pittsburgh, Pennsylvania, United States
University of Texas Southwestern
🇺🇸Dallas, Texas, United States
St. Vincents Hospital
🇦🇺Sydney, New South Wales, Australia
Beth Israel Deacones Medical Center
🇺🇸Boston, Massachusetts, United States
Tufts Medical Center
🇺🇸Boston, Massachusetts, United States
Brigham and Women's Hospital
🇺🇸Boston, Massachusetts, United States
Boston University Medical Center
🇺🇸Boston, Massachusetts, United States
University of California San Diego Medical Center
🇺🇸San Diego, California, United States
University of Miami Medical Center
🇺🇸Miami, Florida, United States
Royal Perth Hospital
🇦🇺Perth, Western Australia, Australia
University of Florida
🇺🇸Gainesville, Florida, United States
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Creighton University Center for Allergy & Asthma
🇺🇸Omaha, Nebraska, United States
University of California at San Francisco
🇺🇸San Francisco, California, United States
Mayo Clinic Rochester
🇺🇸Rochester, Minnesota, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
University of Utah
🇺🇸Salt Lake City, Utah, United States
Kentuckiana Pulmonary Association
🇺🇸Louisville, Kentucky, United States
Suncoast Lung Center
🇺🇸Sarasota, Florida, United States
Temple University School of Medicine
🇺🇸Philadelphia, Pennsylvania, United States
Maine Medical Center
🇺🇸Portland, Maine, United States
University of Chicago
🇺🇸Chicago, Illinois, United States
University of Michigan Health Systems
🇺🇸Ann Arbor, Michigan, United States
Mount Sinai School of Medicine
🇺🇸New York, New York, United States
Washington University
🇺🇸St Louis, Missouri, United States
Columbia University
🇺🇸New York, New York, United States
Winthrop University Hospital
🇺🇸Mineola, New York, United States
Cleveland Clinic Foundation
🇺🇸Cleveland, Ohio, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
Baylor College of Medicine
🇺🇸Houston, Texas, United States
Virginia Commonwealth University Health System
🇺🇸Richmond, Virginia, United States
Peter Loughheed Center- Calgary General Hospital
🇨🇦Calgary, Alberta, Canada
Charite-Universitatsmedizin Berlin
🇩🇪Berlin, Germany
Centre Hospitalier De L'Universite de Montreal
🇨🇦Montreal, Quebec, Canada
Universitat Greifswald
🇩🇪Greifswald, Germany
Toronto General Hospital
🇨🇦Toronto, Ontario, Canada
The Prince Charles Hospital
🇦🇺Chermside, Queensland, Australia
Sir Mortimer B. Davis Jewish General Center
🇨🇦Montreal, Quebec, Canada
Centre de Pneumologie de L'Hospital Laval
🇨🇦Sainte foy, Quebec, Canada
Thorax Klinik
🇩🇪Heidelberg, Germany
Ospedale S.Giuseppe Fatebenefratelli
🇮🇹Milan, Italy
Krankenhaus Donaustauf der LVA
🇩🇪Donaustauf, Germany
Universitatsklinikum Freiburg
🇩🇪Freiburg, Germany
Azienda Ospedaliero Universitaria
🇮🇹Catania, Italy
Presidio Ospedaliero G.B. Morgagni
🇮🇹Forli, Italy
Unita Funzionale di Pneumologia e Fisiopatologia Respiratoria
🇮🇹Milano, Italy
Policlinico Universitario Tor Vergata
🇮🇹Rome, Italy
Royal Hallamshire Hospital
🇬🇧Sheffield, United Kingdom
University College Hosptial
🇬🇧London, United Kingdom
Medizinische Hochschule Hannover
🇩🇪Hannover, Germany
University of California Davis
🇺🇸Davis, California, United States
Stanford University
🇺🇸Stanford, California, United States
University of Colorado Heatlh Sciences Center
🇺🇸Aurora, Colorado, United States
Sarasota Memorial Hospital
🇺🇸Sarasota, Florida, United States
Atlanta Institute for Medical Research
🇺🇸Decatur, Georgia, United States
Dartmouth Medical School
🇺🇸Lebanon, New Hampshire, United States
North Shore Health System
🇺🇸New Hyde Park, New York, United States
Ohio State University
🇺🇸Columbus, Ohio, United States
The Lindner Center for Research & Education at The Christ Hospital
🇺🇸Cincinnati, Ohio, United States
Inova Heart Institiute and Vascular Institute
🇺🇸Falls Church, Virginia, United States
Providence Everett Medical Center
🇺🇸Everett, Washington, United States
Medizinische Universität Wien
🇦🇹Vienna, Austria
University of British Columbia
🇨🇦Vancouver, British Columbia, Canada
London Health Sciences Centre
🇨🇦London, Ontario, Canada
LMU Klinikum der Universitat
🇩🇪Munchen, Germany
Instituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione
🇮🇹Palermo, Italy
Azienda Ospedaliera Universitaria Senese
🇮🇹Siena, Italy
Centro delle Interstiziopatie Polmonari e Malattie Rare del Polmone
🇮🇹Torino, Italy
Azienda Ospedaliera di Padova
🇮🇹Padova, Italy
Papworth Hospital NHS Foundation Trust
🇬🇧Cambridge, United Kingdom
University Hospital Aintree
🇬🇧Liverpool, United Kingdom
University of North Carolina at Chapel Hill
🇺🇸Chapel Hill, North Carolina, United States
Cleveland Clinic Florida
🇺🇸Weston, Florida, United States
Evangelische Lungenklinik Berlin
🇩🇪Berlin, Germany
Alleghany General Hospital
🇺🇸Pittsburgh, Pennsylvania, United States