Abstract | BACKGROUND: 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: 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: PRIMARY FUNDING SOURCE: Gilead Sciences.
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Authors | 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, ARTEMIS-IPF Investigators* |
Journal | Annals of internal medicine
(Ann Intern Med)
Vol. 158
Issue 9
Pg. 641-9
(May 07 2013)
ISSN: 1539-3704 [Electronic] United States |
PMID | 23648946
(Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
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Chemical References |
- Endothelin A Receptor Antagonists
- Phenylpropionates
- Pyridazines
- ambrisentan
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Topics |
- Adult
- Aged
- Aged, 80 and over
- Disease Progression
- Double-Blind Method
- Endothelin A Receptor Antagonists
- Female
- Humans
- Idiopathic Pulmonary Fibrosis
(drug therapy, physiopathology)
- Lung
(physiopathology)
- Male
- Middle Aged
- Phenylpropionates
(adverse effects, therapeutic use)
- Prospective Studies
- Pyridazines
(adverse effects, therapeutic use)
- Treatment Outcome
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