Clinical trial NCT00768300: (ARTEMIS-IPF) Randomized, Placebo-Controlled Study to Evaluate Safety and Effectiveness of Ambrisentan in IPF
Official title: ARTEMIS-IPF: A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multi-Center, Parallel-Group, Event Driven Study to Evaluate the Efficacy and Safety of Ambrisentan in Subjects With Early Idiopathic Pulmonary Fibrosis (IPF)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Idiopathic Pulmonary Fibrosis
Keywords: idiopathic pulmonary fibrosis
interstitial lung disease
ambrisentan
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2008-10-08
Enrollment: 494
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The ARTEMIS-IPF study was conducted to determine if ambrisentan was effective in delaying disease progression and death in participants with idiopathic pulmonary fibrosis (IPF), to evaluate its safety, and to evaluate its effect on development of pulmonary hypertension, quality of life, and dyspnea (shortness of breath) symptoms in this participant population. Participants were randomized in a 2:1 ratio to receive ambrisentan or placebo, respectively. Participation in the study was to be up to 4 years, depending on how long it would take to enroll participants and observe study events. After randomization, visits to the clinic took place every 3 months, and laboratory procedures were performed every month.


Eligibility criteria: Inclusion Criteria:

* Male or females from 40 to 80 years of age
* Diagnosis of IPF
* Honeycombing (fibrosis in the lung) on high-resolution computerised tomography (HRCT) scan of less than or equal to 5%
* Willing and able to have 2 right heart catheterizations performed
* Willing to have monthly lab tests to monitor liver function
* Able to perform the 6 minute walk test (indicated adequate physical function)
* Must have meet lung function requirements
* Normal liver function tests
* Negative serum pregnancy test
* Willing to use at least 2 reliable methods of contraception
* Able to understand and willing to sign informed consent form

Exclusion Criteria:

* No restrictive lung disease (other than usual interstitial pneumonia or IPF)
* No obstructive lung disease
* No recent or active respiratory exacerbations
* No recent hospitalization for an IPF exacerbation
* No recent history of alcohol abuse
* Chronic sildenafil (or same drug class) use for pulmonary hypertension
* Chronic treatment with certain medications for IPF within 30 days of randomization
* No other serious medical conditions

Primary outcomes:
measure: Time to Death or Disease (IPF) Progression.
timeFrame: Up to 48 months
Secondary outcomes:
measure: Proportion of Participants With No Disease Progression or Death at 48 Weeks
timeFrame: Baseline and Week 48
measure: Change in FVC % Predicted at Week 48
timeFrame: Baseline and Week 48
measure: Change in DLCO % Predicted at Week 48
timeFrame: Baseline and Week 48
measure: Change in 6MWT at Week 48
timeFrame: Baseline and Week 48
measure: Change in Quality of Life (QOL) Score at Week 48 as Assessed by the Short-Form 36® (SF-36)
timeFrame: Baseline and Week 48
measure: Change in Quality of Life (QOL) Score at Week 48 as Assessed by the St. George's Respiratory Questionnaire (SGRQ)
timeFrame: Baseline and Week 48
measure: Change in Dyspnea Score at Week 48 as Assessed by the Transitional Dyspnea Index (TDI)
timeFrame: Baseline and Week 48
measure: Percentage of Participants Who Developed PH on Study
timeFrame: Up to 48 weeks
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham Hospital
state: Alabama
city: Phoenix
country: United States
facility: Pulmonary Associates
state: Arizona
city: Scottsdale
country: United States
state: Arizona
city: Los Angeles
country: United States
facility: David Geffen School of Medicine at UCLA(Harbor-UCLA Medical Center)
state: California
city: Sacramento
country: United States
facility: University of California, Davis
state: California
city: San Diego
country: United States
state: California
city: San Francisco
country: United States
state: California
city: Stanford
country: United States
facility: Stanford University
state: California
city: Denver
country: United States
facility: National Jewish Medical And Research Center
state: Colorado
city: Newark
country: United States
state: Delaware
city: Clearwater
country: United States
facility: Bay Area Chest Physicians
state: Florida
city: Miami
country: United States
facility: University of Miami Miller School of Medicine
state: Florida
city: Tampa
country: United States
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Council Bluffs
country: United States
state: Iowa
city: Louisville
country: United States
facility: Kentuckiana Pulmonary Association
state: Kentucky
city: Louisville
country: United States
state: Kentucky
city: Baltimore
country: United States
state: Maryland
city: Baltimore
country: United States
state: Maryland
city: Boston
country: United States
state: Massachusetts
city: Boston
country: United States
state: Massachusetts
city: Ann Arbor
country: United States
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Chesterfield
country: United States
facility: Saint Lukes Foundation
state: Missouri
city: Lebanon
country: United States
facility: Dartmouth Medical School
state: New Hampshire
city: New Brunswick
country: United States
state: New Jersey
city: Piscataway
country: United States
state: New Jersey
city: Summit
country: United States
facility: Pulmonary & Allergy Associates
state: New Jersey
city: Albany
country: United States
facility: Pulmonary And Critical Care Services, P.C.
state: New York
city: Mineola
country: United States
facility: Winthrop University Hospital
state: New York
city: New Hyde Park
country: United States
state: New York
city: New York
country: United States
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cincinnati
country: United States
state: Ohio
city: Cleveland
country: United States
facility: The Cleveland Clinic Foundation
state: Ohio
city: Columbus
country: United States
state: Ohio
city: Portland
country: United States
facility: The Oregon Clinic, P.C.
state: Oregon
city: Philadelphia
country: United States
facility: University of Pennsylvania Health Systems
state: Pennsylvania
city: Philadelphia
country: United States
state: Pennsylvania
city: Pittsburgh
country: United States
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: Reading
country: United States
facility: The Reading Hospital and Medical Center
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Lexington
country: United States
state: South Carolina
city: Spartanburg
country: United States
state: South Carolina
city: Nashville
country: United States
state: Tennessee
city: Houston
country: United States
state: Texas
city: McKinney
country: United States
state: Texas
city: Provo
country: United States
state: Utah
city: Salt Lake City
country: United States
state: Utah
city: Charlottesville
country: United States
state: Virginia
city: Falls Church
country: United States
state: Virginia
city: Lynchburg
country: United States
state: Virginia
city: Everett
country: United States
state: Washington
city: Seattle
country: United States
state: Washington
city: Mar del Plata
country: Argentina
state: Provincia de Buenos Aires
city: Buenos Aires
country: Argentina
city: Ciudad Autonoma de Buenos Aires
country: Argentina
city: Ciudad Autonoma de Buenos Aires
country: Argentina
city: Mar del Plata, Buenos Aires
country: Argentina
city: San Miguel de Tucuman
country: Argentina
city: Concord
country: Australia
state: New South Wales
city: Darlinghurst
country: Australia
state: New South Wales
city: Chermside
country: Australia
state: Queensland
city: Woodville
country: Australia
state: South Australia
city: Hobart
country: Australia
state: Tasmania
city: Parkville
country: Australia
state: Victoria
city: Prahran
country: Australia
state: Victoria
city: Perth
country: Australia
state: Western Australia
city: Graz
country: Austria
city: Innsbruck
country: Austria
city: Linz
country: Austria
city: Wien
country: Austria
city: Anderlecht
country: Belgium
city: Bruxelles
country: Belgium
city: Leuven
country: Belgium
city: Yvoir
country: Belgium
city: Belo Horizonte
country: Brazil
city: Florianopolis
country: Brazil
city: Goiania
country: Brazil
city: Porto Alegre
country: Brazil
city: Porto Alegre
country: Brazil
city: Porto Alegre
country: Brazil
city: Rio de Janeiro
country: Brazil
city: Santo Andre
country: Brazil
city: Sao Paolo
country: Brazil
city: Calgary
country: Canada
state: Alberta
city: Edmondton
country: Canada
state: Alberta
city: Vancouver
country: Canada
state: British Columbia
city: Vancouver
country: Canada
state: British Columbia
city: St. Johns
country: Canada
state: Newfoundland and Labrador
city: Montreal
country: Canada
state: Quebec
city: Sainte Foy
country: Canada
state: Quebec
city: Toronto
country: Canada
city: Santiago
country: Chile
city: Talcahuano
country: Chile
city: Valparaiso
country: Chile
city: Bogota
country: Colombia
city: Floridablanca
country: Colombia
city: Brno
country: Czech Republic
city: Hradec Kralove
country: Czech Republic
city: Jihlava
country: Czech Republic
city: Liberec
country: Czech Republic
city: Olomouc
country: Czech Republic
city: Plzen
country: Czech Republic
city: Lille
country: France
city: Marseille
country: France
city: Montpellier
country: France
city: Nice
country: France
city: Paris
country: France
city: Paris
country: France
city: Pessac
country: France
city: Rennes
country: France
city: Tours
country: France
city: Berlin
country: Germany
city: Berlin
country: Germany
city: Coswig
country: Germany
city: Donaustauf
country: Germany
city: Essen
country: Germany
city: Freiburg
country: Germany
city: Greifswald
country: Germany
city: Heidelberg
country: Germany
city: Lowenstein
country: Germany
city: Munchen
country: Germany
city: Dublin
country: Ireland
city: Ashkelon
country: Israel
city: Beer-Sheva
country: Israel
city: Haifa
country: Israel
city: Haifa
country: Israel
city: Jerusalem
country: Israel
city: Jerusalem
country: Israel
city: Petach Tikva
country: Israel
city: Rehovot
country: Israel
city: Tel Aviv
country: Israel
city: Tel-Hashomer
country: Israel
city: Catania
country: Italy
city: Forlì
country: Italy
city: Milano
country: Italy
city: Milano
country: Italy
city: Modena
country: Italy
city: Napoli
country: Italy
city: Padova
country: Italy
city: Palermo
country: Italy
city: Roma
country: Italy
city: Siena
country: Italy
city: Torino
country: Italy
city: Guadalajara
country: Mexico
state: Jalisco
city: Monterrey
country: Mexico
state: Nuevo Leon
city: Huixquilucan Edo. de Mexico
country: Mexico
city: Mexico City, DF
country: Mexico
city: Monterrey
country: Mexico
city: Zapopan, Jalisco
country: Mexico
city: Almelo
country: Netherlands
city: Callao
country: Peru
city: Lima
country: Peru
city: Lima
country: Peru
city: Lima
country: Peru
city: Lima
country: Peru
city: Lima
country: Peru
city: Bydgoszcz
country: Poland
city: Lodz
country: Poland
city: Cadiz
country: Spain
state: Andalucia
city: Sevilla
country: Spain
facility: Hospital Virgen del Rocio
state: Andalucia
city: Oviedo
country: Spain
state: Asturias
city: Leon
country: Spain
facility: Complejo Asistencial Universitario de León
state: Castilla
city: Pontevedra
country: Spain
state: Galicia
city: Pozuelo de Alarcon
country: Spain
state: Madrid, Communidad de
city: Badalona
country: Spain
city: Barcelona
country: Spain
city: Madrid
country: Spain
city: Basel
country: Switzerland
city: Bern
country: Switzerland
city: Lausanne
country: Switzerland
city: Sheffield
country: United Kingdom
state: South Yorkshire
city: Chertsey
country: United Kingdom
state: Surrey
city: Cambridge
country: United Kingdom
city: Chelmsford
country: United Kingdom
city: Edinburgh
country: United Kingdom
city: Glasgow
country: United Kingdom
city: Liverpool
country: United Kingdom
city: London
country: United Kingdom
city: London
country: United Kingdom
city: Mancesheter
country: United Kingdom
Study officials:
affiliation: University of Washington, Div. of Pulmonary and Critical Care Medicine Chair
name: Ganesh Raghu, MD
role: STUDY_CHAIR
References:
citation: Raghu G, Behr J, Brown KK, Egan JJ, Kawut SM, Flaherty KR, Martinez FJ, Nathan SD, Wells AU, Collard HR, Costabel U, Richeldi L, de Andrade J, Khalil N, Morrison LD, Lederer DJ, Shao L, Li X, Pedersen PS, Montgomery AB, Chien JW, O'Riordan TG; ARTEMIS-IPF Investigators*. Treatment of idiopathic pulmonary fibrosis with ambrisentan: a parallel, randomized trial. Ann Intern Med. 2013 May 7;158(9):641-9. doi: 10.7326/0003-4819-158-9-201305070-00003.
citation: Raghu G, Lynch D, Godwin JD, Webb R, Colby TV, Leslie KO, Behr J, Brown KK, Egan JJ, Flaherty KR, Martinez FJ, Wells AU, Shao L, Zhou H, Pedersen PS, Sood R, Montgomery AB, O'Riordan TG. Diagnosis of idiopathic pulmonary fibrosis with high-resolution CT in patients with little or no radiological evidence of honeycombing: secondary analysis of a randomised, controlled trial. Lancet Respir Med. 2014 Apr;2(4):277-84. doi: 10.1016/S2213-2600(14)70011-6. Epub 2014 Feb 18.
citation: Chien JW, Richards TJ, Gibson KF, Zhang Y, Lindell KO, Shao L, Lyman SK, Adamkewicz JI, Smith V, Kaminski N, O'Riordan T. Serum lysyl oxidase-like 2 levels and idiopathic pulmonary fibrosis disease progression. Eur Respir J. 2014 May;43(5):1430-8. doi: 10.1183/09031936.00141013. Epub 2013 Oct 31.