Treatment of idiopathic pulmonary fibrosis with Ambrisentan: A parallel, randomized trial

Ganesh Raghu, Juergen Behr, Kevin K. Brown, Jim J. Egan, Steven M. Kawut, Kevin R. Flaherty, Fernando J. Martinez, Steven D. Nathan, Athol U. Wells, Harold R. Collard, Ulrich Costabel, Luca Richeldi, Joao De Andrade, Nasreen Khalil, Lake D. Morrison, David J. Lederer, Lixin Shao, Xiaoming Li, Patty S. Pedersen, A. Bruce MontgomeryJason W. Chien, Thomas G. O’Riordan, Devendra Amin, Albert Baker, David Baratz, Robert Baughman, Anthony Cagino, Andrew Chan, Jeffrey Chapman, Francis Cordova, Joao De Andrade, Jeffrey Edelman, Richard Enelow, Neil Ettinger, Marilyn Glassberg, Jeffrey Golden, Jonathan Ilowite, Meryl Kreider, Shahrukh Kureishy, Lisa Lancaster, David Lederer, Andrew Limper, Lake Morrison, Steven Nathan, Mary Strek, Maria Padilla, Micah Fisher, David Riley, Paul Mohabir, Zeenat Safdar, Steven Sahn, Thomas Schaumberg, Mary Beth Scholand, Cecilia Smith, Robert Sussman, Gordon Yung, Rajan Saggar, Joseph Zibrak, Jorge Alvarez, Kevin Chan, Jonathan Ruzi, John McConnell, Jinesh Mehta, George Verghese, Arunabh Talwar, Tarick Haddad, Namita Sood, Hilary Goldberg, Krishna Sundar, Tomasz Ziedalski, Kevin Gibson, Charles Chan, Dale Lien, Charlene Fell, George Fox, Nasreen Khalil, Charles Poirier, Steeve Provencher, Pearce Wilcox, Zeev Vilayi-Weiler, Mordechai Kramer, Mordechai Yigla, Adolfo Baloira, Juergen Behr, Zdenka Parakova, Yehuda Schwarz, Cristina Martinez, Issahar Ben-Dov, Christian Kahler, Antoni Xaubet, Jana Skrickova, Vitezslav Kolek, Helen Parfrey, Jose Echave-Sustaeta, Wim Wuyts, Thomas Geiser, Joachim Muller-Quernheim, Moira Whyte, Michael Pfeifer, Christian Grohe, Lutz Henning Block, Arnaud Bourdin, Horst Olschewski, Yves Sibille, Tomas Snizek, Jiri Vytiska, Milos Pesek, Bruno Crestani, Benoît Wallaert, Pascal Chanez, Dominique Israel Biet, Claire Dromer, Ulrich Costabel, Sven Gläser, Ulrich Wagner, Christian Witt, Felix Herth, Gert Hoeffken, Jim Egan, Raphael Breuer, Yochai Adir, Carlo Agostini, George Cremona, Patrizio Vitulo, Venerino Poletti, Paola Rottoli, Cezary Rybacki, Wojciech Piotrowski, Josep Morera, Keith Hattotuwa, Christopher Warburton, Paul Corris, Colm Leonard, Helen Booth, Mark Britton, Luca Richeldi, Sylvain Marchand-Adam, Charles Hugo Marquette, Michael Tamm, Romain Lazor, George W. Chalmers, Nik Hirani, Paul De Vuyst, Cesare Saltini, Sergio Alfonso Harari, Toby Maher, Federico Campos, Alicia Ramirez, Luis Wehbe, Hector Altieri, Alberto Matsuno Fuchigami, Claudia Cartagena Salinas, Waldo Mattos, Rodolfo Posadas, Elie Fiss, Jesus Diaz-Castanon, Susana Munoz, Luis Natera Ramirez, Julio Chercoff, Carlos Cezar Fritscher, Alexandre Cardoso, Maria Auxiliadora Carmo Moreira, Leila Steidle, Jaquelina Arakaki, Matias Florenzano, Luis Pun Leon, Socorro Ursina Castro Bernardini, Alfredo Gilberto, Carlos Arturo Torres Duque, Carlos Awad, Diego Severiche, Fabio Bolivar Grimaldos, Adalberto Rubin, Carlos Iberico Barrera, Danilo Joel Salazar Ore, Juan Mazzei, Carlos Matiz, Allan Glanville, Peter Hopkins, David Smallwood, Elizabeth Veitch, Michael Musk, Ian Glaspole, Richard Wood-Baker, Antony Veale

Research output: Contribution to journalArticle

308 Scopus citations

Abstract

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, eventdriven 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.

Original languageEnglish (US)
Pages (from-to)641-649
Number of pages9
JournalAnnals of Internal Medicine
Volume158
Issue number9
DOIs
StatePublished - May 7 2013

ASJC Scopus subject areas

  • Internal Medicine

Fingerprint Dive into the research topics of 'Treatment of idiopathic pulmonary fibrosis with Ambrisentan: A parallel, randomized trial'. Together they form a unique fingerprint.

Cite this