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 Montgomery; Jason 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

doi:10.7326/0003-4819-158-9-201305070-00003

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 journal › Article › peer-review

443 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 ET_A 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 language	English (US)
Pages (from-to)	641-649
Number of pages	9
Journal	Annals of Internal Medicine
Volume	158
Issue number	9
DOIs	https://doi.org/10.7326/0003-4819-158-9-201305070-00003
State	Published - May 7 2013

ASJC Scopus subject areas

Internal Medicine

Access to Document

10.7326/0003-4819-158-9-201305070-00003

Cite this

Raghu, G., Behr, J., Brown, K. K., Egan, J. J., Kawut, S. M., Flaherty, K. R., Martinez, F. J., Nathan, S. D., Wells, A. U., Collard, H. R., Costabel, U., Richeldi, L., De Andrade, J., Khalil, N., Morrison, L. D., Lederer, D. J., Shao, L., Li, X., Pedersen, P. S., ... Veale, A. (2013). Treatment of idiopathic pulmonary fibrosis with Ambrisentan: A parallel, randomized trial. Annals of Internal Medicine, 158(9), 641-649. https://doi.org/10.7326/0003-4819-158-9-201305070-00003

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, Amin, D, Baker, A, Baratz, D, Baughman, R, Cagino, A, Chan, A, Chapman, J, Cordova, F, De Andrade, J, Edelman, J, Enelow, R, Ettinger, N, Glassberg, M, Golden, J, Ilowite, J, Kreider, M, Kureishy, S, Lancaster, L, Lederer, D, Limper, A, Morrison, L, Nathan, S, Strek, M, Padilla, M, Fisher, M, Riley, D, Mohabir, P, Safdar, Z, Sahn, S, Schaumberg, T, Beth Scholand, M, Smith, C, Sussman, R, Yung, G, Saggar, R, Zibrak, J, Alvarez, J, Chan, K, Ruzi, J, McConnell, J, Mehta, J, Verghese, G, Talwar, A, Haddad, T, Sood, N, Goldberg, H, Sundar, K, Ziedalski, T, Gibson, K, Chan, C, Lien, D, Fell, C, Fox, G, Khalil, N, Poirier, C, Provencher, S, Wilcox, P, Vilayi-Weiler, Z, Kramer, M, Yigla, M, Baloira, A, Behr, J, Parakova, Z, Schwarz, Y, Martinez, C, Ben-Dov, I, Kahler, C, Xaubet, A, Skrickova, J, Kolek, V, Parfrey, H, Echave-Sustaeta, J, Wuyts, W, Geiser, T, Muller-Quernheim, J, Whyte, M, Pfeifer, M, Grohe, C, Block, LH, Bourdin, A, Olschewski, H, Sibille, Y, Snizek, T, Vytiska, J, Pesek, M, Crestani, B, Wallaert, B, Chanez, P, Israel Biet, D, Dromer, C, Costabel, U, Gläser, S, Wagner, U, Witt, C, Herth, F, Hoeffken, G, Egan, J, Breuer, R, Adir, Y, Agostini, C, Cremona, G, Vitulo, P, Poletti, V, Rottoli, P, Rybacki, C, Piotrowski, W, Morera, J, Hattotuwa, K, Warburton, C, Corris, P, Leonard, C, Booth, H, Britton, M, Richeldi, L, Marchand-Adam, S, Marquette, CH, Tamm, M, Lazor, R, Chalmers, GW, Hirani, N, De Vuyst, P, Saltini, C, Alfonso Harari, S, Maher, T, Campos, F, Ramirez, A, Wehbe, L, Altieri, H, Matsuno Fuchigami, A, Cartagena Salinas, C, Mattos, W, Posadas, R, Fiss, E, Diaz-Castanon, J, Munoz, S, Natera Ramirez, L, Chercoff, J, Cezar Fritscher, C, Cardoso, A, Moreira, MAC, Steidle, L, Arakaki, J, Florenzano, M, Pun Leon, L, Bernardini, SUC, Gilberto, A, Duque, CAT, Awad, C, Severiche, D, Grimaldos, FB, Rubin, A, Barrera, CI, Salazar Ore, DJ, Mazzei, J, Matiz, C, Glanville, A, Hopkins, P, Smallwood, D, Veitch, E, Musk, M, Glaspole, I, Wood-Baker, R & Veale, A 2013, 'Treatment of idiopathic pulmonary fibrosis with Ambrisentan: A parallel, randomized trial', Annals of Internal Medicine, vol. 158, no. 9, pp. 641-649. https://doi.org/10.7326/0003-4819-158-9-201305070-00003

@article{6a31bfea69ec4840aac29a03aa91b0d1,

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

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.",

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

year = "2013",

month = may,

day = "7",

doi = "10.7326/0003-4819-158-9-201305070-00003",

language = "English (US)",

volume = "158",

pages = "641--649",

journal = "Annals of Internal Medicine",

issn = "0003-4819",

publisher = "American College of Physicians",

number = "9",

}

TY - JOUR

T1 - Treatment of idiopathic pulmonary fibrosis with Ambrisentan

T2 - A parallel, randomized trial

AU - Raghu, Ganesh

AU - Behr, Juergen

AU - Brown, Kevin K.

AU - Egan, Jim J.

AU - Kawut, Steven M.

AU - Flaherty, Kevin R.

AU - Martinez, Fernando J.

AU - Nathan, Steven D.

AU - Wells, Athol U.

AU - Collard, Harold R.

AU - Costabel, Ulrich

AU - Richeldi, Luca

AU - De Andrade, Joao

AU - Khalil, Nasreen

AU - Morrison, Lake D.

AU - Lederer, David J.

AU - Shao, Lixin

AU - Li, Xiaoming

AU - Pedersen, Patty S.

AU - Montgomery, A. Bruce

AU - Chien, Jason W.

AU - O’Riordan, Thomas G.

AU - Amin, Devendra

AU - Baker, Albert

AU - Baratz, David

AU - Baughman, Robert

AU - Cagino, Anthony

AU - Chan, Andrew

AU - Chapman, Jeffrey

AU - Cordova, Francis

AU - De Andrade, Joao

AU - Edelman, Jeffrey

AU - Enelow, Richard

AU - Ettinger, Neil

AU - Glassberg, Marilyn

AU - Golden, Jeffrey

AU - Ilowite, Jonathan

AU - Kreider, Meryl

AU - Kureishy, Shahrukh

AU - Lancaster, Lisa

AU - Lederer, David

AU - Limper, Andrew

AU - Morrison, Lake

AU - Nathan, Steven

AU - Strek, Mary

AU - Padilla, Maria

AU - Fisher, Micah

AU - Riley, David

AU - Mohabir, Paul

AU - Safdar, Zeenat

AU - Sahn, Steven

AU - Schaumberg, Thomas

AU - Beth Scholand, Mary

AU - Smith, Cecilia

AU - Sussman, Robert

AU - Yung, Gordon

AU - Saggar, Rajan

AU - Zibrak, Joseph

AU - Alvarez, Jorge

AU - Chan, Kevin

AU - Ruzi, Jonathan

AU - McConnell, John

AU - Mehta, Jinesh

AU - Verghese, George

AU - Talwar, Arunabh

AU - Haddad, Tarick

AU - Sood, Namita

AU - Goldberg, Hilary

AU - Sundar, Krishna

AU - Ziedalski, Tomasz

AU - Gibson, Kevin

AU - Chan, Charles

AU - Lien, Dale

AU - Fell, Charlene

AU - Fox, George

AU - Khalil, Nasreen

AU - Poirier, Charles

AU - Provencher, Steeve

AU - Wilcox, Pearce

AU - Vilayi-Weiler, Zeev

AU - Kramer, Mordechai

AU - Yigla, Mordechai

AU - Baloira, Adolfo

AU - Behr, Juergen

AU - Parakova, Zdenka

AU - Schwarz, Yehuda

AU - Martinez, Cristina

AU - Ben-Dov, Issahar

AU - Kahler, Christian

AU - Xaubet, Antoni

AU - Skrickova, Jana

AU - Kolek, Vitezslav

AU - Parfrey, Helen

AU - Echave-Sustaeta, Jose

AU - Wuyts, Wim

AU - Geiser, Thomas

AU - Muller-Quernheim, Joachim

AU - Whyte, Moira

AU - Pfeifer, Michael

AU - Grohe, Christian

AU - Block, Lutz Henning

AU - Bourdin, Arnaud

AU - Olschewski, Horst

AU - Sibille, Yves

AU - Snizek, Tomas

AU - Vytiska, Jiri

AU - Pesek, Milos

AU - Crestani, Bruno

AU - Wallaert, Benoît

AU - Chanez, Pascal

AU - Israel Biet, Dominique

AU - Dromer, Claire

AU - Costabel, Ulrich

AU - Gläser, Sven

AU - Wagner, Ulrich

AU - Witt, Christian

AU - Herth, Felix

AU - Hoeffken, Gert

AU - Egan, Jim

AU - Breuer, Raphael

AU - Adir, Yochai

AU - Agostini, Carlo

AU - Cremona, George

AU - Vitulo, Patrizio

AU - Poletti, Venerino

AU - Rottoli, Paola

AU - Rybacki, Cezary

AU - Piotrowski, Wojciech

AU - Morera, Josep

AU - Hattotuwa, Keith

AU - Warburton, Christopher

AU - Corris, Paul

AU - Leonard, Colm

AU - Booth, Helen

AU - Britton, Mark

AU - Richeldi, Luca

AU - Marchand-Adam, Sylvain

AU - Marquette, Charles Hugo

AU - Tamm, Michael

AU - Lazor, Romain

AU - Chalmers, George W.

AU - Hirani, Nik

AU - De Vuyst, Paul

AU - Saltini, Cesare

AU - Alfonso Harari, Sergio

AU - Maher, Toby

AU - Campos, Federico

AU - Ramirez, Alicia

AU - Wehbe, Luis

AU - Altieri, Hector

AU - Matsuno Fuchigami, Alberto

AU - Cartagena Salinas, Claudia

AU - Mattos, Waldo

AU - Posadas, Rodolfo

AU - Fiss, Elie

AU - Diaz-Castanon, Jesus

AU - Munoz, Susana

AU - Natera Ramirez, Luis

AU - Chercoff, Julio

AU - Cezar Fritscher, Carlos

AU - Cardoso, Alexandre

AU - Moreira, Maria Auxiliadora Carmo

AU - Steidle, Leila

AU - Arakaki, Jaquelina

AU - Florenzano, Matias

AU - Pun Leon, Luis

AU - Bernardini, Socorro Ursina Castro

AU - Gilberto, Alfredo

AU - Duque, Carlos Arturo Torres

AU - Awad, Carlos

AU - Severiche, Diego

AU - Grimaldos, Fabio Bolivar

AU - Rubin, Adalberto

AU - Barrera, Carlos Iberico

AU - Salazar Ore, Danilo Joel

AU - Mazzei, Juan

AU - Matiz, Carlos

AU - Glanville, Allan

AU - Hopkins, Peter

AU - Smallwood, David

AU - Veitch, Elizabeth

AU - Musk, Michael

AU - Glaspole, Ian

AU - Wood-Baker, Richard

AU - Veale, Antony

PY - 2013/5/7

Y1 - 2013/5/7

N2 - 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.

AB - 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.

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U2 - 10.7326/0003-4819-158-9-201305070-00003

DO - 10.7326/0003-4819-158-9-201305070-00003

M3 - Article

C2 - 23648946

SN - 0003-4819

VL - 158

SP - 641

EP - 649

JO - Annals of Internal Medicine

JF - Annals of Internal Medicine

IS - 9

ER -

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

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