Drotrecogin Alfa (Activated) in Adults with Septic Shock
V Marco Ranieri, B Taylor Thompson, Philip S Barie, Jean-Francois Dhainaut, Ivor S Douglas, Simon Finfer, Bengt Gardlund, John C Marshall, Andrew Rhodes, Antonio Artigas, Didier Payen, Jyrki Tenhunen, Hussein R Al-Khalidi, Vivian Thompson, Jonathan Janes, William L Macias, Burkhard Vangerow, Mark D Williams
NEW ENGLAND JOURNAL OF MEDICINE | MASSACHUSETTS MEDICAL SOC | Published : 2012
BACKGROUND: There have been conflicting reports on the efficacy of recombinant human activated protein C, or drotrecogin alfa (activated) (DrotAA), for the treatment of patients with septic shock. METHODS: In this randomized, double-blind, placebo-controlled, multicenter trial, we assigned 1697 patients with infection, systemic inflammation, and shock who were receiving fluids and vasopressors above a threshold dose for 4 hours to receive either DrotAA (at a dose of 24 μg per kilogram of body weight per hour) or placebo for 96 hours. The primary outcome was death from any cause 28 days after randomization. RESULTS: At 28 days, 223 of 846 patients (26.4%) in the DrotAA group and 202 of 834 (2..View full abstract
Dr. Ranieri reports serving as a member of a data and safety monitoring board for Biotest and an advisory board member for Hemodec and Maquet; Dr. Thompson, serving as the chair of a data and safety monitoring board for AstraZeneca and as an advisory board member for Hemodec, receiving consulting fees from Abbott, Sanofi-Aventis, Immunetrics, US Biotest, Sirius Genomics, and Eli Lilly; Dr. Barie, receiving consulting fees from Eisai and lecture fees from Eli Lilly; Dr. Douglas, receiving grant support from Eli Lilly, Eisai, and Agennix and serving as cochair for the International Guidelines Committee for the 2012 Surviving Sepsis Campaign; Dr. Finfer, receiving consulting fees from Eisai, being a member of the International Sepsis Forum (ISF), and receiving travel support from ISF corporate sponsors; Dr. Marshall, receiving consulting fees from Eisai, Idaho Technology, Roche Diagnostics, Bayer, Vertex Technologies, Pfizer, Daiichi Sankyo, and Hoffmann-La Roche, receiving grant support and travel expenses from BioMerieux, serving as a member of the ISF and receiving travel support from ISF corporate sponsors, serving as a member of the Center for Sepsis Control and Care at the University of Jena and as a member of the data and safety monitoring board for Artisan Pharma, Leo Pharma, Celgene Therapeutics, and Therapeutic Monitoring Systems, and serving as a steering committee member for Spectral Diagnostics and Eisai; Dr. Rhodes, serving on advisory boards for LiDCO and BioMerieux and receiving lecture fees from Edwards, LiDCO, and Covidien; all the preceding authors, or their institutions, received financial support from Eli Lilly for time spent performing committee activities and for travel; Dr. Artigas, receiving travel support and lecture fees and grant support and support for patient recruitment (through his institution) from Eli Lilly, serving on advisory boards for Gambro and Hemodec, and receiving consulting fees from Brahms; Dr. Payen, serving on an advisory board for Homeostasie Consulting and receiving consulting and lecture fees from Homeostasie Consulting and institutional grant support from Naturalia et Biologia; Dr. Tenhunen, receiving institutional grant support for lectures, travel expenses, and data analysis from Eli Lilly; Dr. Al-Khalidi and Ms. Thompson, being employees of the Duke Clinical Research Institute, which received financial support for statistical analysis, preparation of study reports, manuscript review and writing, and travel from Eli Lilly; and Drs. Janes, Macias, Vangerow, and Williams, being current or former employees of and having an equity interest in Eli Lilly. No other potential conflict of interest relevant to this article was reported.