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Treatment of idiopathic pulmonary fibrosis with ambrisentan: a parallel, randomized trial.

Publication ,  Journal Article
Raghu, G; Behr, J; Brown, KK; Egan, JJ; Kawut, SM; Flaherty, KR; Martinez, FJ; Nathan, SD; Wells, AU; Collard, HR; Costabel, U; Richeldi, L ...
Published in: Ann Intern Med
May 7, 2013

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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Published In

Ann Intern Med

DOI

EISSN

1539-3704

Publication Date

May 7, 2013

Volume

158

Issue

9

Start / End Page

641 / 649

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Pyridazines
  • Prospective Studies
  • Phenylpropionates
  • Middle Aged
  • Male
  • Lung
  • Idiopathic Pulmonary Fibrosis
  • Humans
  • General & Internal Medicine
 

Citation

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Raghu, G., Behr, J., Brown, K. K., Egan, J. J., Kawut, S. M., Flaherty, K. R., … ARTEMIS-IPF Investigators*, . (2013). Treatment of idiopathic pulmonary fibrosis with ambrisentan: a parallel, randomized trial. Ann Intern Med, 158(9), 641–649. https://doi.org/10.7326/0003-4819-158-9-201305070-00003
Raghu, Ganesh, Juergen Behr, Kevin K. Brown, Jim J. Egan, Steven M. Kawut, Kevin R. Flaherty, Fernando J. Martinez, et al. “Treatment of idiopathic pulmonary fibrosis with ambrisentan: a parallel, randomized trial.Ann Intern Med 158, no. 9 (May 7, 2013): 641–49. https://doi.org/10.7326/0003-4819-158-9-201305070-00003.
Raghu G, Behr J, Brown KK, Egan JJ, Kawut SM, Flaherty KR, et al. Treatment of idiopathic pulmonary fibrosis with ambrisentan: a parallel, randomized trial. Ann Intern Med. 2013 May 7;158(9):641–9.
Raghu, Ganesh, et al. “Treatment of idiopathic pulmonary fibrosis with ambrisentan: a parallel, randomized trial.Ann Intern Med, vol. 158, no. 9, May 2013, pp. 641–49. Pubmed, doi: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, ARTEMIS-IPF Investigators*. Treatment of idiopathic pulmonary fibrosis with ambrisentan: a parallel, randomized trial. Ann Intern Med. 2013 May 7;158(9):641–649.

Published In

Ann Intern Med

DOI

EISSN

1539-3704

Publication Date

May 7, 2013

Volume

158

Issue

9

Start / End Page

641 / 649

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Pyridazines
  • Prospective Studies
  • Phenylpropionates
  • Middle Aged
  • Male
  • Lung
  • Idiopathic Pulmonary Fibrosis
  • Humans
  • General & Internal Medicine