(ARTEMIS-IPF) Randomized, Placebo-Controlled Study to Evaluate Safety and Effectiveness of Ambrisentan in IPF

NCT00768300 | Terminated Phase 3 Results DMC

• 1 other identifier: GS-US-231-0101
• Study Type: interventional
• Target: 494
• Locations: 21 countries
• Sites: 181

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.

Conditions

Idiopathic Pulmonary Fibrosis

Keywords

idiopathic pulmonary fibrosis; interstitial lung disease; ambrisentan

Outcome Measures

Primary Outcomes (1)

• Time to Death or Disease (IPF) Progression.

  The median time to death or disease progression was based on Kaplan-Meier (KM) estimates of pooling over strata, and was defined as the first occurrence of any of the following: * Either 1) a decrease of ≥ 10% in FVC (L) and a decrease of ≥ 5% in diffuse lung capacity for carbon monoxide (DLCO) (ml/min/mmHg), or 2) a decrease of ≥ 5% in FVC (L) and a decrease of ≥ 15% in DLCO (ml/min/mmHg); deterioration in FVC and DLCO must be confirmed at the subsequent visit within 28 (± 14) days * Respiratory hospitalization (hospitalization involving worsening of, or deterioration in respiratory symptoms, gas exchange/hypoxemia, or radiographic findings on chest x-ray or high-resolution computerised tomography (HRCT) scan * All-cause mortality

  Up to 48 months

Secondary Outcomes (8)

• Proportion of Participants With No Disease Progression or Death at 48 Weeks

  Baseline and Week 48

• Change in FVC % Predicted at Week 48

  Baseline and Week 48

• Change in DLCO % Predicted at Week 48

  Baseline and Week 48

• Change in 6MWT at Week 48

  Baseline and Week 48

• Change in Quality of Life (QOL) Score at Week 48 as Assessed by the Short-Form 36® (SF-36)

  Baseline and Week 48

Study Arms (2)

Ambrisentan

EXPERIMENTAL

Drug: Ambrisentan

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Ambrisentan DRUG

Ambrisentan (5mg or 10 mg tablet) was administered orally once daily.

Also known as: Letairis®

Ambrisentan

Placebo DRUG

Placebo to match ambrisentan was administered orally once daily.

Placebo

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (185)

University of Alabama at Birmingham Hospital

Birmingham, Alabama, 35294, United States

Location

Pulmonary Associates

Phoenix, Arizona, 85006, United States

Location

Unknown Facility

Scottsdale, Arizona, 85258, United States

Location

David Geffen School of Medicine at UCLA(Harbor-UCLA Medical Center)

Los Angeles, California, 90095, United States

Location

University of California, Davis

Sacramento, California, 95817, United States

Location

Unknown Facility

San Diego, California, 92103-8373, United States

Location

Unknown Facility

San Francisco, California, 94143, United States

Location

Stanford University

Stanford, California, 94305, United States

Location

National Jewish Medical And Research Center

Denver, Colorado, 80206, United States

Location

Unknown Facility

Newark, Delaware, 19713, United States

Location

Bay Area Chest Physicians

Clearwater, Florida, 33756, United States

Location

University of Miami Miller School of Medicine

Miami, Florida, 33136, United States

Location

Unknown Facility

Tampa, Florida, 33606, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Unknown Facility

Council Bluffs, Iowa, 51503, United States

Location

Kentuckiana Pulmonary Association

Louisville, Kentucky, 40202, United States

Location

Unknown Facility

Louisville, Kentucky, 40202, United States

Location

Unknown Facility

Baltimore, Maryland, 21201, United States

Location

Unknown Facility

Baltimore, Maryland, 21205, United States

Location

Unknown Facility

Boston, Massachusetts, 02115, United States

Location

Unknown Facility

Boston, Massachusetts, 02215, United States

Location

Unknown Facility

Ann Arbor, Michigan, 48109, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Saint Lukes Foundation

Chesterfield, Missouri, 63017, United States

Location

Dartmouth Medical School

Lebanon, New Hampshire, 03756, United States

Location

Unknown Facility

New Brunswick, New Jersey, 08903, United States

Location

Unknown Facility

Piscataway, New Jersey, 08854, United States

Location

Pulmonary & Allergy Associates

Summit, New Jersey, 07091, United States

Location

Pulmonary And Critical Care Services, P.C.

Albany, New York, 12205, United States

Location

Winthrop University Hospital

Mineola, New York, 11501, United States

Location

Unknown Facility

New Hyde Park, New York, 11040, United States

Location

Unknown Facility

New York, New York, 10029, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Unknown Facility

Cincinnati, Ohio, 45267, United States

Location

The Cleveland Clinic Foundation

Cleveland, Ohio, 44795, United States

Location

Unknown Facility

Columbus, Ohio, 43215, United States

Location

The Oregon Clinic, P.C.

Portland, Oregon, 97220, United States

Location

University of Pennsylvania Health Systems

Philadelphia, Pennsylvania, 19104, United States

Location

Unknown Facility

Philadelphia, Pennsylvania, 19140, United States

Location

Unknown Facility

Pittsburgh, Pennsylvania, 15212, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

The Reading Hospital and Medical Center

Reading, Pennsylvania, 19611, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Unknown Facility

Lexington, South Carolina, 29072, United States

Location

Unknown Facility

Spartanburg, South Carolina, 29303, United States

Location

Unknown Facility

Nashville, Tennessee, 37232, United States

Location

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Houston, Texas, 77030, United States

Location

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McKinney, Texas, 75069, United States

Location

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Provo, Utah, 84604, United States

Location

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Salt Lake City, Utah, 84108, United States

Location

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Charlottesville, Virginia, 22908, United States

Location

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Falls Church, Virginia, 22042, United States

Location

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Lynchburg, Virginia, 24501, United States

Location

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Everett, Washington, 98201, United States

Location

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Seattle, Washington, 98195, United States

Location

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Mar del Plata, Buenos Aires, B7602DCK, Argentina

Location

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Buenos Aires, C1181ACH, Argentina

Location

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Buenos Aires, C1280AEB, Argentina

Location

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Buenos Aires, C1425DES, Argentina

Location

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Mar Del Plata, Buenos Aires, B7602DCK, Argentina

Location

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San Miguel de Tucumán, T4000HXU, Argentina

Location

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Concord, New South Wales, 2139, Australia

Location

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Darlinghurst, New South Wales, 2010, Australia

Location

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Chermside, Queensland, 4032, Australia

Location

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Woodville, South Australia, 5011, Australia

Location

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Hobart, Tasmania, 7000, Australia

Location

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Parkville, Victoria, 3050, Australia

Location

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Prahran, Victoria, 3181, Australia

Location

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Perth, Western Australia, 6000, Australia

Location

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Graz, 8036, Austria

Location

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Innsbruck, 6020, Austria

Location

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Linz, 4020, Austria

Location

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Vienna, 1090, Austria

Location

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Anderlecht, 1070, Belgium

Location

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Brussels, 1200, Belgium

Location

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Leuven, 3000, Belgium

Location

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Yvoir, 5530, Belgium

Location

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São Paulo, São Paulo, 04023-062, Brazil

Location

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Belo Horizonte, 30430-1, Brazil

Location

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Florianópolis, 88040-970, Brazil

Location

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Goiânia, 74605-050, Brazil

Location

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Porto Alegre, 90035-074, Brazil

Location

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Porto Alegre, 90610-000, Brazil

Location

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Porto Alegre, 91350-200, Brazil

Location

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Rio de Janeiro, 21949-900, Brazil

Location

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Santo André, 09060-650, Brazil

Location

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Calgary, Alberta, T1Y6J4, Canada

Location

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Edmondton, Alberta, T6G 2C8, Canada

Location

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Vancouver, British Columbia, V5Z 1M9, Canada

Location

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Vancouver, British Columbia, V6Z 1YP, Canada

Location

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St. John's, Newfoundland and Labrador, A1B 3V6, Canada

Location

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Montreal, Quebec, H2W1T8, Canada

Location

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Sainte-Foy, Quebec, G1V 4G5, Canada

Location

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Toronto, M4X1104, Canada

Location

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Santiago, 7500691, Chile

Location

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Talcahuano, 4270918, Chile

Location

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Valparaíso, 2352499, Chile

Location

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Bogotá, Colombia

Location

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Floridablanca, Colombia

Location

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Brno, 625-00, Czechia

Location

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Hradec Králové, 500 05, Czechia

Location

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Jihlava, 586 33, Czechia

Location

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Liberec, 460 63, Czechia

Location

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Olomouc, 775-20, Czechia

Location

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Pilsen, 305 99, Czechia

Location

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Lille, 59037, France

Location

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Marseille, 13009, France

Location

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Montpellier, 34295, France

Location

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Nice, 06002, France

Location

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Paris, 75015, France

Location

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Paris, 75018, France

Location

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Pessac, 33604, France

Location

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Rennes, 35033, France

Location

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Tours, 37044, France

Location

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Berlin, 10117, Germany

Location

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Berlin, D-13125, Germany

Location

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Coswig, 01640, Germany

Location

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Donaustauf, 93093, Germany

Location

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Essen, D-45239, Germany

Location

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Freiburg im Breisgau, 79106, Germany

Location

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Greifswald, D-17475, Germany

Location

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Heidelberg, 69126, Germany

Location

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Löwenstein, D-74245, Germany

Location

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München, 81377, Germany

Location

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Dublin, 7, Ireland

Location

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Ashkelon, 78306, Israel

Location

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Beersheba, 84101, Israel

Location

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Haifa, 31096, Israel

Location

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Haifa, 34362, Israel

Location

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Jerusalem, 91031, Israel

Location

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Jerusalem, 91120, Israel

Location

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Petah Tikva, 49100, Israel

Location

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Rehovot, 76100, Israel

Location

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Tel Aviv, 64239, Israel

Location

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Tel Litwinsky, 52621, Israel

Location

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Catania, 95123, Italy

Location

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Forlì, 47100, Italy

Location

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Milan, 20123, Italy

Location

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Milan, 20132, Italy

Location

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Modena, 41100, Italy

Location

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Napoli, 80131, Italy

Location

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Padua, 35128, Italy

Location

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Palermo, 90127, Italy

Location

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Roma, 00133, Italy

Location

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Siena, 53100, Italy

Location

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Torino, 10043, Italy

Location

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Guadalajara, Jalisco, 44670, Mexico

Location

Unknown Facility

Monterrey, Nuevo León, 64718, Mexico

Location

Unknown Facility

Huixquilucan Edo. de Mexico, 52763, Mexico

Location

Unknown Facility

Mexico City, DF, 14080, Mexico

Location

Unknown Facility

Monterrey, 64460, Mexico

Location

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Zapopan, Jalisco, 45200, Mexico

Location

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Almelo, 7609 PP, Netherlands

Location

Unknown Facility

Callao, Callao 02, Peru

Location

Unknown Facility

Lima, L31, Peru

Location

Unknown Facility

Lima, L33, Peru

Location

Unknown Facility

Lima, Lima 01, Peru

Location

Unknown Facility

Lima, Lima 27, Peru

Location

Unknown Facility

Lima, Lima 41, Peru

Location

Unknown Facility

Bydgoszcz, 85-681, Poland

Location

Unknown Facility

Lodz, 90-153, Poland

Location

Unknown Facility

Cadiz, Andalusia, 11009, Spain

Location

Hospital Virgen del Rocio

Seville, Andalusia, 41011, Spain

Location

Complejo Asistencial Universitario de León

León, Castilla, 24080, Spain

Location

Unknown Facility

Pontevedra, Galicia, 36071, Spain

Location

Unknown Facility

Pozuelo de Alarcón, Madrid, Communidad de, 28223, Spain

Location

Unknown Facility

Oviedo, Principality of Asturias, 33006, Spain

Location

Unknown Facility

Badalona, 08916, Spain

Location

Unknown Facility

Barcelona, 08036, Spain

Location

Unknown Facility

Madrid, 28007, Spain

Location

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Basel, 4031, Switzerland

Location

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Bern, 3010, Switzerland

Location

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Lausanne, 1011, Switzerland

Location

Unknown Facility

Sheffield, South Yorkshire, S10 2JF, United Kingdom

Location

Unknown Facility

Chertsey, Surrey, KT16 0PZ, United Kingdom

Location

Unknown Facility

Cambridge, CB2 2QQ, United Kingdom

Location

Unknown Facility

Chelmsford, CM1 7ET, United Kingdom

Location

Unknown Facility

Edinburgh, EH16 4SA, United Kingdom

Location

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Glasgow, G4 0SF, United Kingdom

Location

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Liverpool, L9 7AL, United Kingdom

Location

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London, NW1 2PG, United Kingdom

Location

Unknown Facility

London, SW3 6NP, United Kingdom

Location

Unknown Facility

Mancesheter, M23 9LT, United Kingdom

Location

Related Publications (3)

• 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.

  PMID: 23648946 RESULT

• 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.

  PMID: 24717624 DERIVED

• 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.

  PMID: 24177001 DERIVED

MeSH Terms

Conditions

Idiopathic Pulmonary Fibrosis; Lung Diseases, Interstitial

Interventions

ambrisentan

Condition Hierarchy (Ancestors)

Pulmonary Fibrosis; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Clinical Trial Disclosures
• Organization: Gilead Sciences, Inc.

ClinicalTrialDisclosures@gilead.com

Study Officials

• Ganesh Raghu, MD

  University of Washington, Div. of Pulmonary and Critical Care Medicine Chair

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 7, 2008
• First Posted: October 8, 2008
• Study Start: December 1, 2008
• Primary Completion: February 1, 2011
• Study Completion: February 1, 2011
• Last Updated: April 8, 2014
• Results First Posted: April 8, 2014

Record last verified: 2014-02

Locations

AU (8); CA (8); PE (6); ES (9); US (57); AR (6); FR (9); GB (10); CO (2); PL (2); IE (1); IT (11); CZ (6); CH (3); IL (10); ME (6); BE (4); NL (1); CL (3); DE (10); BR (9)