Clinical trial NCT00879229: ARTEMIS-PH - Study of Ambrisentan in Subjects With Pulmonary Hypertension Associated With Idiopathic Pulmonary Fibrosis
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Idiopathic Pulmonary Fibrosis
Pulmonary Hypertension
Keywords: Idiopathic Pulmonary Fibrosis
Pulmonary Hypertension
PH
IPF
Ambrisentan
ERA
Endothelin Receptor Antagonist
Cardiovascular
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2009-04-09
Enrollment: 40
Sex: ALL
Minimum age (years): 35
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Change From Baseline in Six-minute Walk Distance (6MWD).
timeFrame: Baseline to Week 16
Secondary outcomes:
measure: Long-term Survival
timeFrame: Week 48
measure: Transition Dyspnea Index (TDI)
timeFrame: Baseline to Week 16
measure: Change From Baseline in WHO Functional Class
timeFrame: Baseline to Week 16
measure: Change From Baseline in Forced Vital Capacity (FVC) Percent Predicted
timeFrame: Baseline to Week 16
measure: Change From Baseline in N-terminal Pro-B-type Natriuretic Peptide (NT-proBNP)
timeFrame: Baseline to Week 16
measure: Change From Baseline in the Borg Dyspnea Index (BORG) Immediately Following Exercise
timeFrame: Baseline to Week 16
measure: Hemoglobin-corrected Diffusing Capacity for Carbon Monoxide (DLCO) Percent Predicted
timeFrame: Baseline to Week 16
measure: Change in Quality of Life (QOL) Score as Assessed by the Short-Form 36® (SF-36)
timeFrame: Baseline to Week 16
measure: Change in QOL Score as Assessed by the St. George's Respiratory Questionnaire (SRGQ)
timeFrame: Baseline to Week 16
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Scottsdale
country: United States
facility: Mayo Clinic Arizona
state: Arizona
city: Davis
country: United States
facility: University of California Davis
state: California
city: Los Angeles
country: United States
facility: David Geffen School of Medicine UCLA
state: California
city: San Diego
country: United States
facility: University of California San Diego Medical Center
state: California
city: San Francisco
country: United States
facility: University of California at San Francisco
state: California
city: Stanford
country: United States
facility: Stanford University
state: California
city: Aurora
country: United States
facility: University of Colorado Heatlh Sciences Center
state: Colorado
city: Clearwater
country: United States
facility: Bay Area Chest Physicians
state: Florida
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Miami
country: United States
facility: University of Miami Medical Center
state: Florida
city: Sarasota
country: United States
facility: Suncoast Lung Center
state: Florida
city: Sarasota
country: United States
facility: Sarasota Memorial Hospital
state: Florida
city: Weston
country: United States
facility: Cleveland Clinic Florida
state: Florida
city: Decatur
country: United States
facility: Atlanta Institute for Medical Research
state: Georgia
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Louisville
country: United States
facility: Kentuckiana Pulmonary Association
state: Kentucky
city: Portland
country: United States
facility: Maine Medical Center
state: Maine
city: Baltimore
country: United States
facility: Johns Hopkins University School of Medicine
state: Maryland
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Boston University Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deacones Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Health Systems
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic Rochester
state: Minnesota
city: St Louis
country: United States
facility: Washington University
state: Missouri
city: Omaha
country: United States
facility: Creighton University Center for Allergy & Asthma
state: Nebraska
city: Lebanon
country: United States
facility: Dartmouth Medical School
state: New Hampshire
city: Albany
country: United States
facility: Albany Medical Center
state: New York
city: Mineola
country: United States
facility: Winthrop University Hospital
state: New York
city: New Hyde Park
country: United States
facility: North Shore Health System
state: New York
city: New York
country: United States
facility: Mount Sinai School of Medicine
state: New York
city: New York
country: United States
facility: Columbia University
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cincinnati
country: United States
facility: The Lindner Center for Research & Education at The Christ Hospital
state: Ohio
city: Cleveland
country: United States
facility: University Hospitals of Cleveland Case Western
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Temple University School of Medicine
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Alleghany General Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Cancer Institute
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Dallas
country: United States
facility: University of Texas Southwestern
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Falls Church
country: United States
facility: Inova Heart Institiute and Vascular Institute
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University Health System
state: Virginia
city: Everett
country: United States
facility: Providence Everett Medical Center
state: Washington
city: Sydney
country: Australia
facility: St. Vincents Hospital
state: New South Wales
city: Chermside
country: Australia
facility: The Prince Charles Hospital
state: Queensland
city: Perth
country: Australia
facility: Royal Perth Hospital
state: Western Australia
city: Graz
country: Austria
facility: Medizinische Universität Graz
city: Innsbruck
country: Austria
facility: Universitatsklinikum Innsbruck
city: Vienna
country: Austria
facility: Medizinische Universität Wien
city: Calgary
country: Canada
facility: Peter Loughheed Center- Calgary General Hospital
state: Alberta
city: Vancouver
country: Canada
facility: University of British Columbia
state: British Columbia
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
city: Toronto
country: Canada
facility: Toronto General Hospital
state: Ontario
city: Montreal
country: Canada
facility: Centre Hospitalier De L'Universite de Montreal
state: Quebec
city: Montreal
country: Canada
facility: Sir Mortimer B. Davis Jewish General Center
state: Quebec
city: Sainte foy
country: Canada
facility: Centre de Pneumologie de L'Hospital Laval
state: Quebec
city: Berlin
country: Germany
facility: Evangelische Lungenklinik Berlin
city: Berlin
country: Germany
facility: Charite-Universitatsmedizin Berlin
city: Donaustauf
country: Germany
facility: Krankenhaus Donaustauf der LVA
city: Freiburg
country: Germany
facility: Universitatsklinikum Freiburg
city: Greifswald
country: Germany
facility: Universitat Greifswald
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Heidelberg
country: Germany
facility: Thorax Klinik
city: Munchen
country: Germany
facility: LMU Klinikum der Universitat
city: Catania
country: Italy
facility: Azienda Ospedaliero Universitaria
city: Forli
country: Italy
facility: Presidio Ospedaliero G.B. Morgagni
city: Milano
country: Italy
facility: Unita Funzionale di Pneumologia e Fisiopatologia Respiratoria
city: Milan
country: Italy
facility: Ospedale S.Giuseppe Fatebenefratelli
city: Padova
country: Italy
facility: Azienda Ospedaliera di Padova
city: Palermo
country: Italy
facility: Instituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione
city: Rome
country: Italy
facility: Policlinico Universitario Tor Vergata
city: Siena
country: Italy
facility: Azienda Ospedaliera Universitaria Senese
city: Torino
country: Italy
facility: Centro delle Interstiziopatie Polmonari e Malattie Rare del Polmone
city: Cambridge
country: United Kingdom
facility: Papworth Hospital NHS Foundation Trust
city: Liverpool
country: United Kingdom
facility: University Hospital Aintree
city: London
country: United Kingdom
facility: University College Hosptial
city: Sheffield
country: United Kingdom
facility: Royal Hallamshire Hospital
Study officials:
affiliation: Gilead Sciences
name: Hunter Gillies, M.D.
role: STUDY_DIRECTOR
References:
citation: Ruocco G, Cekorja B, Rottoli P, Refini RM, Pellegrini M, Di Tommaso C, Del Castillo G, Franci B, Nuti R, Palazzuoli A. Role of BNP and echo measurement for pulmonary hypertension recognition in patients with interstitial lung disease: An algorithm application model. Respir Med. 2015 Mar;109(3):406-15. doi: 10.1016/j.rmed.2014.12.011. Epub 2015 Jan 3.