ARTEMIS-PH - Study of Ambrisentan in Subjects With Pulmonary Hypertension Associated With Idiopathic Pulmonary Fibrosis

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT00879229
First received: April 8, 2009
Last updated: May 5, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
Idiopathic Pulmonary Fibrosis
Pulmonary Hypertension
Drug: Ambrisentan
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multi-Center, Parallel-Group Study to Evaluate the Efficacy and Safety of Ambrisentan in Subjects With Idiopathic Pulmonary Fibrosis and Pulmonary Hypertension

Resource links provided by NLM:


Further study details as provided by Gilead Sciences:

Primary Outcome Measures:
  • Change From Baseline in Six-minute Walk Distance (6MWD). [ Time Frame: Baseline to Week 16 ] [ Designated as safety issue: No ]
    The change from baseline in 6MWD at Week 16 (end of blinded treatment) was evaluated.


Secondary Outcome Measures:
  • Long-term Survival [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    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) [ Time Frame: Baseline to Week 16 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline to Week 16 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline to Week 16 ] [ Designated as safety issue: No ]
    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) [ Time Frame: Baseline to Week 16 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline to Week 16 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline to Week 16 ] [ Designated as safety issue: No ]
    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) [ Time Frame: Baseline to Week 16 ] [ Designated as safety issue: No ]
    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) [ Time Frame: Baseline to Week 16 ] [ Designated as safety issue: No ]
    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.


Enrollment: 40
Study Start Date: July 2009
Study Completion Date: February 2011
Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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
Drug: Ambrisentan
Ambrisentan (5 mg or 10 mg tablet) administered orally once daily.
Other Name: Letairis
Placebo Comparator: 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.
Drug: Ambrisentan
Ambrisentan (5 mg or 10 mg tablet) administered orally once daily.
Other Name: Letairis
Drug: Placebo
Placebo to match ambrisentan administered orally once daily.

  Eligibility

Ages Eligible for Study:   35 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Selected Inclusion Criteria:

  • 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 Exclusion Criteria:

  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00879229

  Hide Study Locations
Locations
United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35294
United States, Arizona
Mayo Clinic Arizona
Scottsdale, Arizona, United States, 85259
United States, California
University of California Davis
Davis, California, United States, 95817
David Geffen School of Medicine UCLA
Los Angeles, California, United States, 90095
University of California San Diego Medical Center
San Diego, California, United States, 92103
University of California at San Francisco
San Francisco, California, United States, 94143
Stanford University
Stanford, California, United States, 94305
United States, Colorado
University of Colorado Heatlh Sciences Center
Aurora, Colorado, United States, 80045
United States, Florida
Bay Area Chest Physicians
Clearwater, Florida, United States, 33756
University of Florida
Gainesville, Florida, United States, 32610
University of Miami Medical Center
Miami, Florida, United States, 33136
Sarasota Memorial Hospital
Sarasota, Florida, United States, 34239
Suncoast Lung Center
Sarasota, Florida, United States, 34233
Cleveland Clinic Florida
Weston, Florida, United States, 33331
United States, Georgia
Atlanta Institute for Medical Research
Decatur, Georgia, United States, 30030
United States, Illinois
University of Chicago
Chicago, Illinois, United States, 60637
United States, Kentucky
Kentuckiana Pulmonary Association
Louisville, Kentucky, United States
United States, Maine
Maine Medical Center
Portland, Maine, United States
United States, Maryland
Johns Hopkins University School of Medicine
Baltimore, Maryland, United States, 21205
United States, Massachusetts
Boston University Medical Center
Boston, Massachusetts, United States, 02118
Brigham and Women's Hospital
Boston, Massachusetts, United States, 02115
Beth Israel Deacones Medical Center
Boston, Massachusetts, United States, 02215
Tufts Medical Center
Boston, Massachusetts, United States, 02111
United States, Michigan
University of Michigan Health Systems
Ann Arbor, Michigan, United States, 48109
United States, Minnesota
Mayo Clinic Rochester
Rochester, Minnesota, United States, 55905
United States, Missouri
Washington University
St Louis, Missouri, United States, 63110
United States, Nebraska
Creighton University Center for Allergy & Asthma
Omaha, Nebraska, United States, 68131
United States, New Hampshire
Dartmouth Medical School
Lebanon, New Hampshire, United States, 03756
United States, New York
Albany Medical Center
Albany, New York, United States, 12208
Winthrop University Hospital
Mineola, New York, United States, 11501
North Shore Health System
New Hyde Park, New York, United States, 11040
Mount Sinai School of Medicine
New York, New York, United States, 10029
Columbia University
New York, New York, United States, 10032
United States, North Carolina
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, United States, 27599
Duke University Medical Center
Durham, North Carolina, United States, 27710
United States, Ohio
The Lindner Center for Research & Education at The Christ Hospital
Cincinnati, Ohio, United States, 45219
Cleveland Clinic Foundation
Cleveland, Ohio, United States, 44195
University Hospitals of Cleveland Case Western
Cleveland, Ohio, United States, 44106
Ohio State University
Columbus, Ohio, United States, 43210
United States, Pennsylvania
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
Temple University School of Medicine
Philadelphia, Pennsylvania, United States, 19140
University of Pittsburgh Cancer Institute
Pittsburgh, Pennsylvania, United States, 15213
Alleghany General Hospital
Pittsburgh, Pennsylvania, United States, 12512
United States, South Carolina
Medical University of South Carolina
Charleston, South Carolina, United States
United States, Tennessee
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37232
United States, Texas
University of Texas Southwestern
Dallas, Texas, United States, 75390
Baylor College of Medicine
Houston, Texas, United States, 77030
United States, Utah
University of Utah
Salt Lake City, Utah, United States, 84108
United States, Virginia
Inova Heart Institiute and Vascular Institute
Falls Church, Virginia, United States, 22042
Virginia Commonwealth University Health System
Richmond, Virginia, United States, 23298
United States, Washington
Providence Everett Medical Center
Everett, Washington, United States, 98201
Australia, New South Wales
St. Vincents Hospital
Sydney, New South Wales, Australia, 2010
Australia, Queensland
The Prince Charles Hospital
Chermside, Queensland, Australia, 4032
Australia, Western Australia
Royal Perth Hospital
Perth, Western Australia, Australia, 6000
Austria
Medizinische Universität Graz
Graz, Austria, 8036
Universitatsklinikum Innsbruck
Innsbruck, Austria
Medizinische Universität Wien
Vienna, Austria, 1090
Canada, Alberta
Peter Loughheed Center- Calgary General Hospital
Calgary, Alberta, Canada, T1Y 6J4
Canada, British Columbia
University of British Columbia
Vancouver, British Columbia, Canada, V5Z 1M9
Canada, Ontario
London Health Sciences Centre
London, Ontario, Canada, N6A 5W9
Toronto General Hospital
Toronto, Ontario, Canada
Canada, Quebec
Centre Hospitalier De L'Universite de Montreal
Montreal, Quebec, Canada, H2W 1T8
Sir Mortimer B. Davis Jewish General Center
Montreal, Quebec, Canada
Centre de Pneumologie de L'Hospital Laval
Sainte foy, Quebec, Canada, G1V 4G5
Germany
Charite-Universitatsmedizin Berlin
Berlin, Germany
Evangelische Lungenklinik Berlin
Berlin, Germany, 13125
Krankenhaus Donaustauf der LVA
Donaustauf, Germany, 93093
Universitatsklinikum Freiburg
Freiburg, Germany, 79095
Universitat Greifswald
Greifswald, Germany, 17475
Medizinische Hochschule Hannover
Hannover, Germany, 30625
Thorax Klinik
Heidelberg, Germany, 66126
LMU Klinikum der Universitat
Munchen, Germany
Italy
Azienda Ospedaliero Universitaria
Catania, Italy
Presidio Ospedaliero G.B. Morgagni
Forli, Italy
Ospedale S.Giuseppe Fatebenefratelli
Milan, Italy
Unita Funzionale di Pneumologia e Fisiopatologia Respiratoria
Milano, Italy, 20132
Azienda Ospedaliera di Padova
Padova, Italy
Instituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione
Palermo, Italy
Policlinico Universitario Tor Vergata
Rome, Italy
Azienda Ospedaliera Universitaria Senese
Siena, Italy, 53100
Centro delle Interstiziopatie Polmonari e Malattie Rare del Polmone
Torino, Italy, 10043
United Kingdom
Papworth Hospital NHS Foundation Trust
Cambridge, United Kingdom, CB23 3RE
University Hospital Aintree
Liverpool, United Kingdom
University College Hosptial
London, United Kingdom
Royal Hallamshire Hospital
Sheffield, United Kingdom
Sponsors and Collaborators
Gilead Sciences
Investigators
Study Director: Hunter Gillies, M.D. Gilead Sciences
  More Information

No publications provided

Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT00879229     History of Changes
Other Study ID Numbers: GS-US-300-0128
Study First Received: April 8, 2009
Results First Received: August 9, 2013
Last Updated: May 5, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Gilead Sciences:
Idiopathic Pulmonary Fibrosis
Pulmonary Hypertension
PH
IPF
Ambrisentan
ERA
Endothelin Receptor Antagonist
Cardiovascular

Additional relevant MeSH terms:
Hypertension
Fibrosis
Hypertension, Pulmonary
Pulmonary Fibrosis
Idiopathic Pulmonary Fibrosis
Vascular Diseases
Cardiovascular Diseases
Pathologic Processes
Lung Diseases
Respiratory Tract Diseases
Idiopathic Interstitial Pneumonias
Lung Diseases, Interstitial

ClinicalTrials.gov processed this record on October 01, 2014