Original Research
7 May 2013

Treatment of Idiopathic Pulmonary Fibrosis With Ambrisentan: A Parallel, Randomized Trial

Publication: Annals of Internal Medicine
Volume 158, Number 9

Abstract

This article has been corrected. The original version (PDF) is appended to this article as a Supplement.

Background:

Idiopathic pulmonary fibrosis (IPF) is characterized by formation and proliferation of fibroblast foci. Endothelin-1 induces lung fibroblast proliferation and contractile activity via the endothelin A (ETA) receptor.

Objective:

To determine whether ambrisentan, an ETA receptor–selective antagonist, reduces the rate of IPF progression.

Design:

Randomized, double-blind, placebo-controlled, event-driven trial. (ClinicalTrials.gov: NCT00768300)

Setting:

Academic and private hospitals.

Participants:

Patients with IPF aged 40 to 80 years with minimal or no honeycombing on high-resolution computed tomography scans.

Intervention:

Ambrisentan, 10 mg/d, or placebo.

Measurements:

Time to disease progression, defined as death, respiratory hospitalization, or a categorical decrease in lung function.

Results:

The study was terminated after enrollment of 492 patients (75% of intended enrollment; mean duration of exposure to study medication, 34.7 weeks) because an interim analysis indicated a low likelihood of showing efficacy for the end point by the scheduled end of the study. Ambrisentan-treated patients were more likely to meet the prespecified criteria for disease progression (90 [27.4%] vs. 28 [17.2%] patients; P = 0.010; hazard ratio, 1.74 [95% CI, 1.14 to 2.66]). Lung function decline was seen in 55 (16.7%) ambrisentan-treated patients and 19 (11.7%) placebo-treated patients (P = 0.109). Respiratory hospitalizations were seen in 44 (13.4%) and 9 (5.5%) patients in the ambrisentan and placebo groups, respectively (P = 0.007). Twenty-six (7.9%) patients who received ambrisentan and 6 (3.7%) who received placebo died (P = 0.100). Thirty-two (10%) ambrisentan-treated patients and 16 (10%) placebo-treated patients had pulmonary hypertension at baseline, and analysis stratified by the presence of pulmonary hypertension revealed similar results for the primary end point.

Limitation:

The study was terminated early.

Conclusion:

Ambrisentan was not effective in treating IPF and may be associated with an increased risk for disease progression and respiratory hospitalizations.

Primary Funding Source:

Gilead Sciences.

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Supplemental Material

Supplement. Original Version (PDF).

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Information & Authors

Information

Published In

cover image Annals of Internal Medicine
Annals of Internal Medicine
Volume 158Number 97 May 2013
Pages: 641 - 649

History

Published online: 7 May 2013
Published in issue: 7 May 2013

Keywords

Authors

Affiliations

Ganesh Raghu, MD
From University of Washington, Gilead Sciences, and Cardeas Pharma, Seattle, Washington; University Hospital Bergmannsheil, Bochum, and Ruhrlandklinik Essen, Universitätsklinik, Essen, Germany; University of Colorado, Denver, Colorado; Mater Misericordiae Hospital, Dublin, Ireland; University of Pennsylvania, Philadelphia, Pennsylvania; University of Michigan, Ann Arbor, Michigan; Inova Fairfax Hospital, Falls Church, Virginia; Royal Brompton Hospital, London, United Kingdom;
University of California, San Francisco, San Francisco, California; Azienda Ospedaliero-Universitaria di Modena Policlinic, Modena, Italy; University of Alabama at Birmingham Hospital, Birmingham, Alabama; University of British Columbia, Vancouver, British Columbia, Canada; Duke University Medical Center, Durham, North Carolina; and Columbia University Medical Center, New York, New York.
Juergen Behr, MD
From University of Washington, Gilead Sciences, and Cardeas Pharma, Seattle, Washington; University Hospital Bergmannsheil, Bochum, and Ruhrlandklinik Essen, Universitätsklinik, Essen, Germany; University of Colorado, Denver, Colorado; Mater Misericordiae Hospital, Dublin, Ireland; University of Pennsylvania, Philadelphia, Pennsylvania; University of Michigan, Ann Arbor, Michigan; Inova Fairfax Hospital, Falls Church, Virginia; Royal Brompton Hospital, London, United Kingdom;
University of California, San Francisco, San Francisco, California; Azienda Ospedaliero-Universitaria di Modena Policlinic, Modena, Italy; University of Alabama at Birmingham Hospital, Birmingham, Alabama; University of British Columbia, Vancouver, British Columbia, Canada; Duke University Medical Center, Durham, North Carolina; and Columbia University Medical Center, New York, New York.
Kevin K. Brown, MD
From University of Washington, Gilead Sciences, and Cardeas Pharma, Seattle, Washington; University Hospital Bergmannsheil, Bochum, and Ruhrlandklinik Essen, Universitätsklinik, Essen, Germany; University of Colorado, Denver, Colorado; Mater Misericordiae Hospital, Dublin, Ireland; University of Pennsylvania, Philadelphia, Pennsylvania; University of Michigan, Ann Arbor, Michigan; Inova Fairfax Hospital, Falls Church, Virginia; Royal Brompton Hospital, London, United Kingdom;
University of California, San Francisco, San Francisco, California; Azienda Ospedaliero-Universitaria di Modena Policlinic, Modena, Italy; University of Alabama at Birmingham Hospital, Birmingham, Alabama; University of British Columbia, Vancouver, British Columbia, Canada; Duke University Medical Center, Durham, North Carolina; and Columbia University Medical Center, New York, New York.
Jim J. Egan, MD
From University of Washington, Gilead Sciences, and Cardeas Pharma, Seattle, Washington; University Hospital Bergmannsheil, Bochum, and Ruhrlandklinik Essen, Universitätsklinik, Essen, Germany; University of Colorado, Denver, Colorado; Mater Misericordiae Hospital, Dublin, Ireland; University of Pennsylvania, Philadelphia, Pennsylvania; University of Michigan, Ann Arbor, Michigan; Inova Fairfax Hospital, Falls Church, Virginia; Royal Brompton Hospital, London, United Kingdom;
University of California, San Francisco, San Francisco, California; Azienda Ospedaliero-Universitaria di Modena Policlinic, Modena, Italy; University of Alabama at Birmingham Hospital, Birmingham, Alabama; University of British Columbia, Vancouver, British Columbia, Canada; Duke University Medical Center, Durham, North Carolina; and Columbia University Medical Center, New York, New York.
Steven M. Kawut, MD
From University of Washington, Gilead Sciences, and Cardeas Pharma, Seattle, Washington; University Hospital Bergmannsheil, Bochum, and Ruhrlandklinik Essen, Universitätsklinik, Essen, Germany; University of Colorado, Denver, Colorado; Mater Misericordiae Hospital, Dublin, Ireland; University of Pennsylvania, Philadelphia, Pennsylvania; University of Michigan, Ann Arbor, Michigan; Inova Fairfax Hospital, Falls Church, Virginia; Royal Brompton Hospital, London, United Kingdom;
University of California, San Francisco, San Francisco, California; Azienda Ospedaliero-Universitaria di Modena Policlinic, Modena, Italy; University of Alabama at Birmingham Hospital, Birmingham, Alabama; University of British Columbia, Vancouver, British Columbia, Canada; Duke University Medical Center, Durham, North Carolina; and Columbia University Medical Center, New York, New York.
Kevin R. Flaherty, MD
From University of Washington, Gilead Sciences, and Cardeas Pharma, Seattle, Washington; University Hospital Bergmannsheil, Bochum, and Ruhrlandklinik Essen, Universitätsklinik, Essen, Germany; University of Colorado, Denver, Colorado; Mater Misericordiae Hospital, Dublin, Ireland; University of Pennsylvania, Philadelphia, Pennsylvania; University of Michigan, Ann Arbor, Michigan; Inova Fairfax Hospital, Falls Church, Virginia; Royal Brompton Hospital, London, United Kingdom;
University of California, San Francisco, San Francisco, California; Azienda Ospedaliero-Universitaria di Modena Policlinic, Modena, Italy; University of Alabama at Birmingham Hospital, Birmingham, Alabama; University of British Columbia, Vancouver, British Columbia, Canada; Duke University Medical Center, Durham, North Carolina; and Columbia University Medical Center, New York, New York.
Fernando J. Martinez, MD
From University of Washington, Gilead Sciences, and Cardeas Pharma, Seattle, Washington; University Hospital Bergmannsheil, Bochum, and Ruhrlandklinik Essen, Universitätsklinik, Essen, Germany; University of Colorado, Denver, Colorado; Mater Misericordiae Hospital, Dublin, Ireland; University of Pennsylvania, Philadelphia, Pennsylvania; University of Michigan, Ann Arbor, Michigan; Inova Fairfax Hospital, Falls Church, Virginia; Royal Brompton Hospital, London, United Kingdom;
University of California, San Francisco, San Francisco, California; Azienda Ospedaliero-Universitaria di Modena Policlinic, Modena, Italy; University of Alabama at Birmingham Hospital, Birmingham, Alabama; University of British Columbia, Vancouver, British Columbia, Canada; Duke University Medical Center, Durham, North Carolina; and Columbia University Medical Center, New York, New York.
Steven D. Nathan, MD
From University of Washington, Gilead Sciences, and Cardeas Pharma, Seattle, Washington; University Hospital Bergmannsheil, Bochum, and Ruhrlandklinik Essen, Universitätsklinik, Essen, Germany; University of Colorado, Denver, Colorado; Mater Misericordiae Hospital, Dublin, Ireland; University of Pennsylvania, Philadelphia, Pennsylvania; University of Michigan, Ann Arbor, Michigan; Inova Fairfax Hospital, Falls Church, Virginia; Royal Brompton Hospital, London, United Kingdom;
University of California, San Francisco, San Francisco, California; Azienda Ospedaliero-Universitaria di Modena Policlinic, Modena, Italy; University of Alabama at Birmingham Hospital, Birmingham, Alabama; University of British Columbia, Vancouver, British Columbia, Canada; Duke University Medical Center, Durham, North Carolina; and Columbia University Medical Center, New York, New York.
Athol U. Wells, MD
From University of Washington, Gilead Sciences, and Cardeas Pharma, Seattle, Washington; University Hospital Bergmannsheil, Bochum, and Ruhrlandklinik Essen, Universitätsklinik, Essen, Germany; University of Colorado, Denver, Colorado; Mater Misericordiae Hospital, Dublin, Ireland; University of Pennsylvania, Philadelphia, Pennsylvania; University of Michigan, Ann Arbor, Michigan; Inova Fairfax Hospital, Falls Church, Virginia; Royal Brompton Hospital, London, United Kingdom;
University of California, San Francisco, San Francisco, California; Azienda Ospedaliero-Universitaria di Modena Policlinic, Modena, Italy; University of Alabama at Birmingham Hospital, Birmingham, Alabama; University of British Columbia, Vancouver, British Columbia, Canada; Duke University Medical Center, Durham, North Carolina; and Columbia University Medical Center, New York, New York.
Harold R. Collard, MD
From University of Washington, Gilead Sciences, and Cardeas Pharma, Seattle, Washington; University Hospital Bergmannsheil, Bochum, and Ruhrlandklinik Essen, Universitätsklinik, Essen, Germany; University of Colorado, Denver, Colorado; Mater Misericordiae Hospital, Dublin, Ireland; University of Pennsylvania, Philadelphia, Pennsylvania; University of Michigan, Ann Arbor, Michigan; Inova Fairfax Hospital, Falls Church, Virginia; Royal Brompton Hospital, London, United Kingdom;
University of California, San Francisco, San Francisco, California; Azienda Ospedaliero-Universitaria di Modena Policlinic, Modena, Italy; University of Alabama at Birmingham Hospital, Birmingham, Alabama; University of British Columbia, Vancouver, British Columbia, Canada; Duke University Medical Center, Durham, North Carolina; and Columbia University Medical Center, New York, New York.
Ulrich Costabel, MD
From University of Washington, Gilead Sciences, and Cardeas Pharma, Seattle, Washington; University Hospital Bergmannsheil, Bochum, and Ruhrlandklinik Essen, Universitätsklinik, Essen, Germany; University of Colorado, Denver, Colorado; Mater Misericordiae Hospital, Dublin, Ireland; University of Pennsylvania, Philadelphia, Pennsylvania; University of Michigan, Ann Arbor, Michigan; Inova Fairfax Hospital, Falls Church, Virginia; Royal Brompton Hospital, London, United Kingdom;
University of California, San Francisco, San Francisco, California; Azienda Ospedaliero-Universitaria di Modena Policlinic, Modena, Italy; University of Alabama at Birmingham Hospital, Birmingham, Alabama; University of British Columbia, Vancouver, British Columbia, Canada; Duke University Medical Center, Durham, North Carolina; and Columbia University Medical Center, New York, New York.
Luca Richeldi, MD
From University of Washington, Gilead Sciences, and Cardeas Pharma, Seattle, Washington; University Hospital Bergmannsheil, Bochum, and Ruhrlandklinik Essen, Universitätsklinik, Essen, Germany; University of Colorado, Denver, Colorado; Mater Misericordiae Hospital, Dublin, Ireland; University of Pennsylvania, Philadelphia, Pennsylvania; University of Michigan, Ann Arbor, Michigan; Inova Fairfax Hospital, Falls Church, Virginia; Royal Brompton Hospital, London, United Kingdom;
University of California, San Francisco, San Francisco, California; Azienda Ospedaliero-Universitaria di Modena Policlinic, Modena, Italy; University of Alabama at Birmingham Hospital, Birmingham, Alabama; University of British Columbia, Vancouver, British Columbia, Canada; Duke University Medical Center, Durham, North Carolina; and Columbia University Medical Center, New York, New York.
Joao de Andrade, MD
From University of Washington, Gilead Sciences, and Cardeas Pharma, Seattle, Washington; University Hospital Bergmannsheil, Bochum, and Ruhrlandklinik Essen, Universitätsklinik, Essen, Germany; University of Colorado, Denver, Colorado; Mater Misericordiae Hospital, Dublin, Ireland; University of Pennsylvania, Philadelphia, Pennsylvania; University of Michigan, Ann Arbor, Michigan; Inova Fairfax Hospital, Falls Church, Virginia; Royal Brompton Hospital, London, United Kingdom;
University of California, San Francisco, San Francisco, California; Azienda Ospedaliero-Universitaria di Modena Policlinic, Modena, Italy; University of Alabama at Birmingham Hospital, Birmingham, Alabama; University of British Columbia, Vancouver, British Columbia, Canada; Duke University Medical Center, Durham, North Carolina; and Columbia University Medical Center, New York, New York.
Nasreen Khalil, MD
From University of Washington, Gilead Sciences, and Cardeas Pharma, Seattle, Washington; University Hospital Bergmannsheil, Bochum, and Ruhrlandklinik Essen, Universitätsklinik, Essen, Germany; University of Colorado, Denver, Colorado; Mater Misericordiae Hospital, Dublin, Ireland; University of Pennsylvania, Philadelphia, Pennsylvania; University of Michigan, Ann Arbor, Michigan; Inova Fairfax Hospital, Falls Church, Virginia; Royal Brompton Hospital, London, United Kingdom;
University of California, San Francisco, San Francisco, California; Azienda Ospedaliero-Universitaria di Modena Policlinic, Modena, Italy; University of Alabama at Birmingham Hospital, Birmingham, Alabama; University of British Columbia, Vancouver, British Columbia, Canada; Duke University Medical Center, Durham, North Carolina; and Columbia University Medical Center, New York, New York.
Lake D. Morrison, MD
From University of Washington, Gilead Sciences, and Cardeas Pharma, Seattle, Washington; University Hospital Bergmannsheil, Bochum, and Ruhrlandklinik Essen, Universitätsklinik, Essen, Germany; University of Colorado, Denver, Colorado; Mater Misericordiae Hospital, Dublin, Ireland; University of Pennsylvania, Philadelphia, Pennsylvania; University of Michigan, Ann Arbor, Michigan; Inova Fairfax Hospital, Falls Church, Virginia; Royal Brompton Hospital, London, United Kingdom;
University of California, San Francisco, San Francisco, California; Azienda Ospedaliero-Universitaria di Modena Policlinic, Modena, Italy; University of Alabama at Birmingham Hospital, Birmingham, Alabama; University of British Columbia, Vancouver, British Columbia, Canada; Duke University Medical Center, Durham, North Carolina; and Columbia University Medical Center, New York, New York.
David J. Lederer, MD
From University of Washington, Gilead Sciences, and Cardeas Pharma, Seattle, Washington; University Hospital Bergmannsheil, Bochum, and Ruhrlandklinik Essen, Universitätsklinik, Essen, Germany; University of Colorado, Denver, Colorado; Mater Misericordiae Hospital, Dublin, Ireland; University of Pennsylvania, Philadelphia, Pennsylvania; University of Michigan, Ann Arbor, Michigan; Inova Fairfax Hospital, Falls Church, Virginia; Royal Brompton Hospital, London, United Kingdom;
University of California, San Francisco, San Francisco, California; Azienda Ospedaliero-Universitaria di Modena Policlinic, Modena, Italy; University of Alabama at Birmingham Hospital, Birmingham, Alabama; University of British Columbia, Vancouver, British Columbia, Canada; Duke University Medical Center, Durham, North Carolina; and Columbia University Medical Center, New York, New York.
Lixin Shao, MD
From University of Washington, Gilead Sciences, and Cardeas Pharma, Seattle, Washington; University Hospital Bergmannsheil, Bochum, and Ruhrlandklinik Essen, Universitätsklinik, Essen, Germany; University of Colorado, Denver, Colorado; Mater Misericordiae Hospital, Dublin, Ireland; University of Pennsylvania, Philadelphia, Pennsylvania; University of Michigan, Ann Arbor, Michigan; Inova Fairfax Hospital, Falls Church, Virginia; Royal Brompton Hospital, London, United Kingdom;
University of California, San Francisco, San Francisco, California; Azienda Ospedaliero-Universitaria di Modena Policlinic, Modena, Italy; University of Alabama at Birmingham Hospital, Birmingham, Alabama; University of British Columbia, Vancouver, British Columbia, Canada; Duke University Medical Center, Durham, North Carolina; and Columbia University Medical Center, New York, New York.
Xiaoming Li, PhD
From University of Washington, Gilead Sciences, and Cardeas Pharma, Seattle, Washington; University Hospital Bergmannsheil, Bochum, and Ruhrlandklinik Essen, Universitätsklinik, Essen, Germany; University of Colorado, Denver, Colorado; Mater Misericordiae Hospital, Dublin, Ireland; University of Pennsylvania, Philadelphia, Pennsylvania; University of Michigan, Ann Arbor, Michigan; Inova Fairfax Hospital, Falls Church, Virginia; Royal Brompton Hospital, London, United Kingdom;
University of California, San Francisco, San Francisco, California; Azienda Ospedaliero-Universitaria di Modena Policlinic, Modena, Italy; University of Alabama at Birmingham Hospital, Birmingham, Alabama; University of British Columbia, Vancouver, British Columbia, Canada; Duke University Medical Center, Durham, North Carolina; and Columbia University Medical Center, New York, New York.
Patty S. Pedersen, BSN
From University of Washington, Gilead Sciences, and Cardeas Pharma, Seattle, Washington; University Hospital Bergmannsheil, Bochum, and Ruhrlandklinik Essen, Universitätsklinik, Essen, Germany; University of Colorado, Denver, Colorado; Mater Misericordiae Hospital, Dublin, Ireland; University of Pennsylvania, Philadelphia, Pennsylvania; University of Michigan, Ann Arbor, Michigan; Inova Fairfax Hospital, Falls Church, Virginia; Royal Brompton Hospital, London, United Kingdom;
University of California, San Francisco, San Francisco, California; Azienda Ospedaliero-Universitaria di Modena Policlinic, Modena, Italy; University of Alabama at Birmingham Hospital, Birmingham, Alabama; University of British Columbia, Vancouver, British Columbia, Canada; Duke University Medical Center, Durham, North Carolina; and Columbia University Medical Center, New York, New York.
A. Bruce Montgomery, MD
From University of Washington, Gilead Sciences, and Cardeas Pharma, Seattle, Washington; University Hospital Bergmannsheil, Bochum, and Ruhrlandklinik Essen, Universitätsklinik, Essen, Germany; University of Colorado, Denver, Colorado; Mater Misericordiae Hospital, Dublin, Ireland; University of Pennsylvania, Philadelphia, Pennsylvania; University of Michigan, Ann Arbor, Michigan; Inova Fairfax Hospital, Falls Church, Virginia; Royal Brompton Hospital, London, United Kingdom;
University of California, San Francisco, San Francisco, California; Azienda Ospedaliero-Universitaria di Modena Policlinic, Modena, Italy; University of Alabama at Birmingham Hospital, Birmingham, Alabama; University of British Columbia, Vancouver, British Columbia, Canada; Duke University Medical Center, Durham, North Carolina; and Columbia University Medical Center, New York, New York.
Jason W. Chien, MD
From University of Washington, Gilead Sciences, and Cardeas Pharma, Seattle, Washington; University Hospital Bergmannsheil, Bochum, and Ruhrlandklinik Essen, Universitätsklinik, Essen, Germany; University of Colorado, Denver, Colorado; Mater Misericordiae Hospital, Dublin, Ireland; University of Pennsylvania, Philadelphia, Pennsylvania; University of Michigan, Ann Arbor, Michigan; Inova Fairfax Hospital, Falls Church, Virginia; Royal Brompton Hospital, London, United Kingdom;
University of California, San Francisco, San Francisco, California; Azienda Ospedaliero-Universitaria di Modena Policlinic, Modena, Italy; University of Alabama at Birmingham Hospital, Birmingham, Alabama; University of British Columbia, Vancouver, British Columbia, Canada; Duke University Medical Center, Durham, North Carolina; and Columbia University Medical Center, New York, New York.
Thomas G. O'Riordan, MD
From University of Washington, Gilead Sciences, and Cardeas Pharma, Seattle, Washington; University Hospital Bergmannsheil, Bochum, and Ruhrlandklinik Essen, Universitätsklinik, Essen, Germany; University of Colorado, Denver, Colorado; Mater Misericordiae Hospital, Dublin, Ireland; University of Pennsylvania, Philadelphia, Pennsylvania; University of Michigan, Ann Arbor, Michigan; Inova Fairfax Hospital, Falls Church, Virginia; Royal Brompton Hospital, London, United Kingdom;
University of California, San Francisco, San Francisco, California; Azienda Ospedaliero-Universitaria di Modena Policlinic, Modena, Italy; University of Alabama at Birmingham Hospital, Birmingham, Alabama; University of British Columbia, Vancouver, British Columbia, Canada; Duke University Medical Center, Durham, North Carolina; and Columbia University Medical Center, New York, New York.
the ARTEMIS-IPF Investigators
Acknowledgment: The authors thank Paul Noble, MD; Vincent Cottin, MD; Teresa DeMarco, MD; and Charles S. Davis, PhD, of the Data Monitoring Committee for monitoring the study and making recommendations. They also thank Todd DeVries, PhD, for providing statistical guidance and support when employed by Gilead Sciences, and all of the clinical site investigators, coordinators, and patients for participating in this study.
Grant Support: By Gilead Sciences.
Reproducible Research Statement: Study protocol: Available from Dr. O'Riordan (e-mail, [email protected]). Statistical code and data set: Requests for access will be considered on a case-by-case basis by Dr. O'Riordan (e-mail, [email protected]).
Corresponding Author: Ganesh Raghu, MD, Division of Pulmonary and Critical Care Medicine, University of Washington Medical Center, 1959 NE Pacific, Campus Box 356175, Seattle, WA 98195.
Current Author Addresses: Dr. Raghu: Division of Pulmonary and Critical Care Medicine, University of Washington Medical Center, 1959 NE Pacific, Campus Box 356175, Seattle, WA 98195.
Dr. Behr: University of Munich, Department of Internal Medicine, Grosshadern, Marchioninistrasse 15, Munich 81377, Germany.
Dr. Brown: National Jewish Health, 1400 Jackson Street, Denver, CO 80206.
Dr. Egan: Mater Misericordiae Hospital, Eccles Street, Dublin 7, Ireland.
Dr. Kawut: University of Pennsylvania, 718 Blockley Hall, 423 Guardian Drive, Philadelphia, PA 19104.
Drs. Flaherty and Martinez: University of Michigan, 1500 East Medical Center Drive, 3916 Taubman Center, Ann Arbor, MI 48109.
Dr. Nathan: Inova Fairfax Hospital, 3300 Gallows Road, Falls Church, VA 22042.
Dr. Wells: Royal Brompton Hospital, Sydney Street, London SW3 6NP, United Kingdom.
Dr. Collard: University of California, San Francisco, 505 Parnassus Avenue, Moffitt, San Francisco, CA 94143.
Dr. Costabel: Universität Duisburg-Essen, Ruhrlandklinik Essen, Universitätsklinik, Tueschener Weg 40, Essen 45239, Germany.
Dr. Richeldi: University of Modena and Reggio Emilia, Via del Pozzo 71, Modena 41100, Italy.
Dr. de Andrade: University of Alabama at Birmingham Hospital, THT 422, 1900 University Boulevard, Birmingham, AL 35294-0006.
Dr. Khalil: 2775 Laurel Street, Vancouver, British Columbia V5Z 1M9, Canada.
Dr. Morrison: Duke University Medical Center, 330 Trent Drive, Durham, NC 27710.
Dr. Lederer: Columbia University, 622 West 168th Street, PH-14, Room 104, New York, NY 10032.
Dr. Shao: Gilead Sciences, Inc., 333 Lakeside Drive, Foster City, CA 94404.
Drs. Li, Chien, and O'Riordan and Ms. Pedersen: Gilead Sciences, Inc., 199 East Blaine Street, Seattle, WA 98102.
Dr. Montgomery: Cardeas Pharma, 2025 First Avenue, Suite 1200, Seattle, WA 98121.
Author Contributions: Conception and design: G. Raghu, J. Behr, K.K. Brown, S.M. Kawut, K.R. Flaherty, F.J. Martinez, S.D. Nathan, A.U. Wells, A.B. Montgomery, T.G. O'Riordan.
Analysis and interpretation of the data: G. Raghu, J. Behr, K.K. Brown, S.M. Kawut, K.R. Flaherty, F.J. Martinez, S.D. Nathan, H.R. Collard, U. Costabel, L. Richeldi, J. de Andrade, D.J. Lederer, L. Shao, X. Li, A.B. Montgomery, T.G. O'Riordan.
Drafting of the article: G. Raghu, S.M. Kawut, K.R. Flaherty, U. Costabel, A.B. Montgomery, J.W. Chien, T.G. O'Riordan.
Critical revision of the article for important intellectual content: G. Raghu, J. Behr, K.K. Brown, S.M. Kawut, F.J. Martinez, S.D. Nathan, A.U. Wells, H.R. Collard, U. Costabel, L. Richeldi, J. de Andrade, D.J. Lederer, T.G. O'Riordan.
Final approval of the article: G. Raghu, J. Behr, K.K. Brown, S.M. Kawut, K.R. Flaherty, F.J. Martinez, S.D. Nathan, A.U. Wells, H.R. Collard, U. Costabel, L. Richeldi, J. de Andrade, N. Khalil, L.D. Morrison, D.J. Lederer, X. Li, A.B. Montgomery, T.G. O'Riordan.
Provision of study materials or patients: G. Raghu, U. Costabel, J. de Andrade, N. Khalil, L.D. Morrison, D.J. Lederer, T.G. O'Riordan.
Statistical expertise: S.M. Kawut, F.J. Martinez, L. Shao, X. Li.
Obtaining of funding: A.B. Montgomery, T.G. O'Riordan.
Administrative, technical, or logistic support: N. Khalil, A.B. Montgomery.
Collection and assembly of data: G. Raghu, X. Li, P.S. Pedersen, T.G. O'Riordan.
* For a list of the ARTEMIS-IPF investigators, see Appendix 1.

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Ganesh Raghu, Juergen Behr, Kevin K. Brown, et al; the ARTEMIS-IPF Investigators . Treatment of Idiopathic Pulmonary Fibrosis With Ambrisentan: A Parallel, Randomized Trial. Ann Intern Med.2013;158:641-649. [Epub 7 May 2013]. doi:10.7326/0003-4819-158-9-201305070-00003

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