Treatment of idiopathic pulmonary fibrosis with Ambrisentan

A parallel, randomized trial

ARTEMIS-IPF Investigators

Research output: Contribution to journalArticle

264 Citations (Scopus)

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

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Idiopathic Pulmonary Fibrosis
Placebos
Therapeutics
Disease Progression
Hospitalization
Pulmonary Hypertension
Lung
Fibroblasts
ambrisentan
Endothelin A Receptors
Private Hospitals
Endothelin-1
Tomography

All Science Journal Classification (ASJC) codes

  • Internal Medicine

Cite this

@article{bbe74292acb84253b66b0cd04968ceab,
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 = "{ARTEMIS-IPF Investigators} and 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’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 Robert Sussman",
year = "2013",
month = "5",
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",

}

Treatment of idiopathic pulmonary fibrosis with Ambrisentan : A parallel, randomized trial. / ARTEMIS-IPF Investigators.

In: Annals of Internal Medicine, Vol. 158, No. 9, 07.05.2013, p. 641-649.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Treatment of idiopathic pulmonary fibrosis with Ambrisentan

T2 - A parallel, randomized trial

AU - ARTEMIS-IPF Investigators

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 - Sussman, Robert

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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EP - 649

JO - Annals of Internal Medicine

JF - Annals of Internal Medicine

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