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Raghu G.,University of Washington | Anstrom K.J.,Duke Clinical Research Institute | King Jr. T.E.,University of California at San Francisco | Lasky J.A.,Tulane University | Martinez F.J.,University of Michigan
New England Journal of Medicine | Year: 2012

BACKGROUND: A combination of prednisone, azathioprine, and N-acetylcysteine (NAC) has been widely used as a treatment for idiopathic pulmonary fibrosis. The safety and efficacy of this three-drug regimen is unknown. METHODS: In this randomized, double-blind, placebo-controlled trial, we assigned patients with idiopathic pulmonary fibrosis who had mild-to-moderate lung-function impairment to one of three groups - receiving a combination of prednisone, azathioprine, and NAC (combination therapy), NAC alone, or placebo - in a 1:1:1 ratio. The primary outcome was the change in longitudinal measurements of forced vital capacity during a 60-week treatment period. RESULTS: When approximately 50% of data had been collected (with 77 patients in the combination- therapy group and 78 in the placebo group), a planned interim analysis revealed that patients in the combination-therapy group, as compared with the placebo group, had an increased rate of death (8 vs. 1, P = 0.01) and hospitalization (23 vs. 7, P<0.001). These observations, coupled with no evidence of physiological or clinical benefit for combination therapy, prompted the independent data and safety monitoring board to recommend termination of the combination-therapy group at a mean follow-up of 32 weeks. Data from the ongoing comparison of the NAC-only group and the placebo group are not reported here. CONCLUSIONS: Increased risks of death and hospitalization were observed in patients with idiopathic pulmonary fibrosis who were treated with a combination of prednisone, azathioprine, and NAC, as compared with placebo. These findings provide evidence against the use of this combination in such patients. (Funded by the National Heart, Lung, and Blood Institute and the Cowlin Family Fund; ClinicalTrials.gov number, NCT00650091.) Copyright © 2012 Massachusetts Medical Society.

Currow D.C.,Flinders University | Abernethy A.P.,Duke Clinical Research Institute
Future Oncology | Year: 2014

Anamorelin hydrochloride is an orally active ghrelin receptor agonist in development by Helsinn, for the treatment of non-small-cell lung cancer (NSCLC) cachexia. In preclinical and clinical studies, the potent affinity of anamorelin for the ghrelin receptor is associated with significant appetite-enhancing activity and resultant improvements in body weight, lean body mass, and handgrip strength compared with placebo. The accompanying stimulatory effects on growth hormone and IGF-1 are not associated with tumor growth, and overall survival in patients with cancer is not compromised. Anamorelin is well tolerated with no dose-limiting toxicities identified to date. The findings of ongoing Phase III studies are needed to confirm the significant potential of anamorelin to treat NSCLC cachexia. © 2014 Future Medicine Ltd.

Hess C.N.,Duke Clinical Research Institute
Journal of the American Heart Association | Year: 2014

Data regarding sex-based outcomes after percutaneous coronary intervention (PCI) for myocardial infarction are mixed. We sought to examine whether sex differences in outcomes exist in contemporary practice. We examined acute myocardial infarction patients undergoing PCI between April 2010 and October 2012 at 210 US hospitals participating in the Treatment with Adenosine Diphosphate Receptor Inhibitors: Longitudinal Assessment of Treatment Patterns and Events after Acute Coronary Syndrome (TRANSLATE-ACS) observational study. Outcomes included 1-year risk of major adverse cardiac events and bleeding according to Global Utilization of Strategies To Open Occluded Arteries (GUSTO) and Bleeding Academic Research Consortium (BARC) definitions. Among 6218 patients, 27.5% (n=1712) were female. Compared with men, women were older, had more comorbidities, and had lower functional status. Use of multivessel PCI and drug-eluting stents was similar between sexes, while women received less prasugrel. Unadjusted cumulative incidence of 1-year major adverse cardiac events was higher for women than for men (15.7% versus 13.6%, P=0.02), but female sex was no longer associated with higher incidence of major adverse cardiac events after multivariable adjustment (hazard ratio 0.98, 95% CI 0.83 to 1.15). Female sex was associated with higher risks of post-PCI GUSTO bleeding (9.1% versus 5.7%, P<0.0001) and postdischarge BARC bleeding (39.6% versus 27.9%, P<0.0001). Differences persisted after adjustment (GUSTO: hazard ratio 1.32, 95% CI 1.06 to 1.64; BARC: incidence rate ratio 1.42, 95% CI 1.27 to 1.56). Female and male myocardial infarction patients undergoing PCI differ regarding demographic, clinical, and treatment profiles. These differences appear to explain the higher observed major adverse cardiac event rate but not higher adjusted bleeding risk for women versus men.

Dauerman H.L.,University of Vermont | Rao S.V.,Duke Clinical Research Institute | Resnic F.S.,Brigham and Womens Hospital | Applegate R.J.,Wake forest University
Journal of the American College of Cardiology | Year: 2011

Bleeding complications after coronary intervention are associated with prolonged hospitalization, increased hospital costs, patient dissatisfaction, morbidity, and 1-year mortality. Bleeding avoidance strategies is a term incorporating multiple modalities that aim to reduce bleeding and vascular complications after cardiovascular catheterization. Recent improvements in the rates of bleeding complications after invasive cardiovascular procedures suggest that the clinical community has successfully embraced specific strategies and improved patient care in this area. There remains controversy regarding the efficacy, safety, and/or practicality of 3 key bleeding avoidance strategies for cardiac catheterization and coronary intervention: procedural (radial artery approach, safezone arteriotomy), pharmacological (multiple agents), and technological (vascular closure devices) approaches to improved access. In this paper, we address areas of consensus with respect to selected modalities in order to define the role of each strategy in current practice. Furthermore, we focus on areas of controversy for selected modalities in order to define key areas warranting cautious clinical approaches and the need for future randomized clinical trials in this area. © 2011 American College of Cardiology Foundation.

Chastain C.A.,Vanderbilt University | Naggie S.,Duke Clinical Research Institute
Current HIV/AIDS Reports | Year: 2013

Hepatitis C (HCV) coinfection is the leading cause of liver-related morbidity and is a leading cause of mortality in human immunodeficiency virus (HIV)-infected individuals in the antiretroviral therapy era. Direct-acting antiviral (DAA) therapies are transforming how HCV is treated with significant improvements in efficacy and tolerability. In this article, DAA agents expected to be available in 2014 are reviewed, including telaprevir, boceprevir, sofosbuvir, simeprevir, faldaprevir, and daclatasvir. Available data regarding clinical efficacy, adverse effects, and drug interactions in HIV-HCV coinfection are discussed. The management of adverse effects of HCV therapy and treatment considerations in patients with cirrhosis are also reviewed. © 2013 Springer Science+Business Media New York.

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