Raghu, Ganesh; Behr, Juergen; Brown, Kevin K.; Egan, Jim J.; Kawut, Steven M.; Flaherty, Kevin R.; Martinez, Fernando J.; Nathan, Steven D.; Wells, Athol U.; Collard, Harold R.; Costabel, Ulrich; Richeldi, Luca; de Andrade, Joao; Khalil, Nasreen; Morrison, Lake D.; Lederer, David J.; Shao, Lixin; Li, Xiaoming; Pedersen, Patty S.; Montgomery, A. Bruce; ... (2013). Treatment of idiopathic pulmonary fibrosis with ambrisentan: a parallel, randomized trial. Annals of internal medicine, 158(9), pp. 641-649. American College of Physicians 10.7326/0003-4819-158-9-201305070-00003
Full text not available from this repository.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.
Item Type: |
Journal Article (Original Article) |
|---|---|
Division/Institute: |
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Forschungsbereich Mu50 > Forschungsgruppe Pneumologie (Erwachsene) 04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Pneumology |
UniBE Contributor: |
Geiser, Thomas (A) |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
0003-4819 |
Publisher: |
American College of Physicians |
Language: |
English |
Submitter: |
Rahel Holderegger |
Date Deposited: |
30 Apr 2014 08:41 |
Last Modified: |
29 Mar 2023 23:33 |
Publisher DOI: |
10.7326/0003-4819-158-9-201305070-00003 |
PubMed ID: |
23648946 |
URI: |
https://boris.unibe.ch/id/eprint/45666 |
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