8 research outputs found
The Visual Cycle in the Inner Retina of Chicken and the Involvement of Retinal G-Protein-Coupled Receptor (RGR)
Comparative and competitive adsorption of cadmium, copper, nickel, and lead ions by Iranian natural zeolite
The Influence of Gut Microbiota on the Cardiovascular System Under Conditions of Obesity and Chronic Stress
Treatment of Idiopathic Pulmonary Fibrosis With Ambrisentan
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%) placebotreated 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. © 2013 American College of Physicians