Drotrecogin alfa (activated) in adults with septic shock
V Marco Ranieri, B Taylor Thompson, Philip S Barie, Jean-François Dhainaut, Ivor S Douglas, Simon Finfer, Bengt Gårdlund, 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, PROWESS-SHOCK Study Group, V Marco Ranieri, B Taylor Thompson, Philip S Barie, Jean-François Dhainaut, Ivor S Douglas, Simon Finfer, Bengt Gårdlund, John C Marshall, Andrew Rhodes, Jonathan Janes, William L Macias, Burkhard Vangerow, Mark D Williams, Arthur S Slutsky, Gordon Guyatt, Derek Angus, Tim Evans, Ray Carroll, Charles Weijer, Robert Boots, David Ernest, Peter Harrigan, Marianne Chapman, Rinaldo Bellomo, Simon Finfer, Chris Wright, Timothy Crozier, Andrew Davies, Craig French, Neil Orford, Anne Leditschke, Michael Reade, Christopher MacIsaac, Thierry Dugernier, Philippe Jorens, Margot Vander Laenen, Manu Malbrain, Wouter Meersseman, Willem Stockman, Francois Damas, Jan Raemaekers, Alain-Michel Dive, Pierre Damas, Peter Rogiers, Pierre-Francois Laterre, Suzana Margareth Ajeje Lobo, José Otavio Costa Auler Jr, Cintia Magalhães Carvalho, Milton Caldeira, Fernando Suparregui Dias, Frederico Bruzzi de Carvalho, Flávia Machado, Pierre Aslanian, Jean-Gilles Guimond, Niall Ferguson, Dan Zuege, Dan Zuege, Dean Chittock, Vinay Dhingra, Dean Chittock, Philippe Rico, Anand Kumar, Bojan Paunovic, Robert Fowler, Olivier Lesur, William Anderson, Niv Sne, R Bruce Light, Vladimir Sramek, Jan Neiser, Jan Pachl, Pavel Sevcik, Ivo Burget, Vladimir Cerny, Renata Parizkova, Eduard Kasal, Martin Balik, Pavel Dlouhy, Jyrki Tenhunen, Jouni Kurola, Ilkka Parviainen, Raili Laru-Sompa, Pekka Loisa, Anne Kuitunen, Ville Pettila, Maija Kaukonen, Kari Saarinen, Charles Santré, Gilles Hilbert, Elie Azoulay, Hervé Mentec, Bruno Levy, Daniel Villers, Gilles Bernardin, Didier Payen, Jean-Luc Diehl, Philippe Montravers, Jacques Duranteau, Yves Cohen, Yannick Malledant, Alain LePape, Fabrice Zéni, Jean-Yves Lefrant, Jean-Pierre Quenot, Jacques Durand-Gasselin, Philippe Guiot, Martine Ferrandiere, Yves Le Tulzo, Qin Lu, Samir Jaber, Claire Gatécel, Karim Asehnoune, Bernard de Jonghe, Jean-Louis Ricome, Pierre Asfar, Bruno Francois, Arnaud Desachy, Emmanuelle Mercier, Laurent Martin-Lefèvre, René Robert, Bernard Allaouchiche, Herwig Gerlach, Johann Motsch, Ulrich Jaschinski, Ralf Kuhlen, Sebastian Kubitza, Stefan Kluge, Juergen Barth, Gernot Marx, Wolfgang Hartl, Norbert Weiler, Sameer Jog, Milind Gadkari, Ratan Gupta, Vijay Kuman Chopra, Amit Varma, Abraham Oomman, Rajashekar Reddy, Omender Singh, Hemant Thacker, Mayakonda Krishnamurthy Ramesh, Giorgio Tulli, Roberto Fumagalli, Giuseppe Gagliardi, Marco Ranieri, Rosairo Urbino, Giulio Minoja, Biagio Panascia, Giacomo Castiglione, Davide Salaris, Massimo Antonelli, Francesco Della Corte, Manuel Nicolás Poblano Morales, Janet Silvia Aguirre Sanchez, Fernando Dolores Aguilera Almazán, José Guillermo Domínguez Cherit, Seton Henderson, Robert Ure, Frank Van Haren, Colin McArthur, Tony Williams, Rui Moreno, Pedro Póvoa, Jose Artur Paiva, Nuno Catorze, Jesus Blanco, Juan-Carlos Ruiz-Rodriguez, Francisco Alvarez, Jordi Rello, Alejandro Rodriguez, Maria-Jesus Lopez, Cesar Perez, Antoni Betbese, Antonio Artigas, Jorge Ibanez, Sergio Ruiz-Santana, Jose Ignacio Gomez, Jesus Rico, Miguel Sanchez, Andres Esteban, Gumersindo Gonzalez, Jose Cambronero, Gonzalo Sirgo, Ramon Claramonte, Tomas Guzman, Marco Maggiorini, Gian-Reto Kleger, Roberto Malacrida, Henk van Leeuwen, Arthur van Zanten, Peter Pickkers, Jeroen Schouten, Abhiram Mallick, Tara Quasim, Mehrun Zuleika, Putul Sarkar, David Pogson, Peter MacNaughton, Andrew Rhodes, Tony Whitehouse, Michael Margarson, Max Jonas, Jeremy Bewley, Dilshan Arawwawala, Stuart McLellan, Alan Davidson, Robert Scott Harris, Jacob Samuel, Robert Birkhahn, David Willms, Brahim Ardolic, Barry Hahn, Ivor Douglas, Richard Albert, Jean Charchaflieh, Svetolik Djurkovic, Joseph Barney, David Striker, Firas Koura, Michael McNellis, Steven Chang, Gyorgy Frendl, Chet Morrison, Melanie Kelly, Kevin Dishman, Antonio Anzueto, Daniel Hagg, Michael Barram, Neil Ettinger, Carolyn Fruci, Ghiath Bayasi, Avinash Kumar, Warren Abel, Maged Tanios, Richard Wunderink, Ronald Rains, Brian Young, William Bekemeyer, Kenneth Krell, Takkin Lo, Patrick Wright, Mark Wilson, Ronald Rains, Patrick Wright, V Marco Ranieri, B Taylor Thompson, Philip S Barie, Jean-François Dhainaut, Ivor S Douglas, Simon Finfer, Bengt Gårdlund, 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, PROWESS-SHOCK Study Group, V Marco Ranieri, B Taylor Thompson, Philip S Barie, Jean-François Dhainaut, Ivor S Douglas, Simon Finfer, Bengt Gårdlund, John C Marshall, Andrew Rhodes, Jonathan Janes, William L Macias, Burkhard Vangerow, Mark D Williams, Arthur S Slutsky, Gordon Guyatt, Derek Angus, Tim Evans, Ray Carroll, Charles Weijer, Robert Boots, David Ernest, Peter Harrigan, Marianne Chapman, Rinaldo Bellomo, Simon Finfer, Chris Wright, Timothy Crozier, Andrew Davies, Craig French, Neil Orford, Anne Leditschke, Michael Reade, Christopher MacIsaac, Thierry Dugernier, Philippe Jorens, Margot Vander Laenen, Manu Malbrain, Wouter Meersseman, Willem Stockman, Francois Damas, Jan Raemaekers, Alain-Michel Dive, Pierre Damas, Peter Rogiers, Pierre-Francois Laterre, Suzana Margareth Ajeje Lobo, José Otavio Costa Auler Jr, Cintia Magalhães Carvalho, Milton Caldeira, Fernando Suparregui Dias, Frederico Bruzzi de Carvalho, Flávia Machado, Pierre Aslanian, Jean-Gilles Guimond, Niall Ferguson, Dan Zuege, Dan Zuege, Dean Chittock, Vinay Dhingra, Dean Chittock, Philippe Rico, Anand Kumar, Bojan Paunovic, Robert Fowler, Olivier Lesur, William Anderson, Niv Sne, R Bruce Light, Vladimir Sramek, Jan Neiser, Jan Pachl, Pavel Sevcik, Ivo Burget, Vladimir Cerny, Renata Parizkova, Eduard Kasal, Martin Balik, Pavel Dlouhy, Jyrki Tenhunen, Jouni Kurola, Ilkka Parviainen, Raili Laru-Sompa, Pekka Loisa, Anne Kuitunen, Ville Pettila, Maija Kaukonen, Kari Saarinen, Charles Santré, Gilles Hilbert, Elie Azoulay, Hervé Mentec, Bruno Levy, Daniel Villers, Gilles Bernardin, Didier Payen, Jean-Luc Diehl, Philippe Montravers, Jacques Duranteau, Yves Cohen, Yannick Malledant, Alain LePape, Fabrice Zéni, Jean-Yves Lefrant, Jean-Pierre Quenot, Jacques Durand-Gasselin, Philippe Guiot, Martine Ferrandiere, Yves Le Tulzo, Qin Lu, Samir Jaber, Claire Gatécel, Karim Asehnoune, Bernard de Jonghe, Jean-Louis Ricome, Pierre Asfar, Bruno Francois, Arnaud Desachy, Emmanuelle Mercier, Laurent Martin-Lefèvre, René Robert, Bernard Allaouchiche, Herwig Gerlach, Johann Motsch, Ulrich Jaschinski, Ralf Kuhlen, Sebastian Kubitza, Stefan Kluge, Juergen Barth, Gernot Marx, Wolfgang Hartl, Norbert Weiler, Sameer Jog, Milind Gadkari, Ratan Gupta, Vijay Kuman Chopra, Amit Varma, Abraham Oomman, Rajashekar Reddy, Omender Singh, Hemant Thacker, Mayakonda Krishnamurthy Ramesh, Giorgio Tulli, Roberto Fumagalli, Giuseppe Gagliardi, Marco Ranieri, Rosairo Urbino, Giulio Minoja, Biagio Panascia, Giacomo Castiglione, Davide Salaris, Massimo Antonelli, Francesco Della Corte, Manuel Nicolás Poblano Morales, Janet Silvia Aguirre Sanchez, Fernando Dolores Aguilera Almazán, José Guillermo Domínguez Cherit, Seton Henderson, Robert Ure, Frank Van Haren, Colin McArthur, Tony Williams, Rui Moreno, Pedro Póvoa, Jose Artur Paiva, Nuno Catorze, Jesus Blanco, Juan-Carlos Ruiz-Rodriguez, Francisco Alvarez, Jordi Rello, Alejandro Rodriguez, Maria-Jesus Lopez, Cesar Perez, Antoni Betbese, Antonio Artigas, Jorge Ibanez, Sergio Ruiz-Santana, Jose Ignacio Gomez, Jesus Rico, Miguel Sanchez, Andres Esteban, Gumersindo Gonzalez, Jose Cambronero, Gonzalo Sirgo, Ramon Claramonte, Tomas Guzman, Marco Maggiorini, Gian-Reto Kleger, Roberto Malacrida, Henk van Leeuwen, Arthur van Zanten, Peter Pickkers, Jeroen Schouten, Abhiram Mallick, Tara Quasim, Mehrun Zuleika, Putul Sarkar, David Pogson, Peter MacNaughton, Andrew Rhodes, Tony Whitehouse, Michael Margarson, Max Jonas, Jeremy Bewley, Dilshan Arawwawala, Stuart McLellan, Alan Davidson, Robert Scott Harris, Jacob Samuel, Robert Birkhahn, David Willms, Brahim Ardolic, Barry Hahn, Ivor Douglas, Richard Albert, Jean Charchaflieh, Svetolik Djurkovic, Joseph Barney, David Striker, Firas Koura, Michael McNellis, Steven Chang, Gyorgy Frendl, Chet Morrison, Melanie Kelly, Kevin Dishman, Antonio Anzueto, Daniel Hagg, Michael Barram, Neil Ettinger, Carolyn Fruci, Ghiath Bayasi, Avinash Kumar, Warren Abel, Maged Tanios, Richard Wunderink, Ronald Rains, Brian Young, William Bekemeyer, Kenneth Krell, Takkin Lo, Patrick Wright, Mark Wilson, Ronald Rains, Patrick Wright
Abstract
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 (24.2%) in the placebo group had died (relative risk in the DrotAA group, 1.09; 95% confidence interval [CI], 0.92 to 1.28; P=0.31). At 90 days, 287 of 842 patients (34.1%) in the DrotAA group and 269 of 822 (32.7%) in the placebo group had died (relative risk, 1.04; 95% CI, 0.90 to 1.19; P=0.56). Among patients with severe protein C deficiency at baseline, 98 of 342 (28.7%) in the DrotAA group had died at 28 days, as compared with 102 of 331 (30.8%) in the placebo group (risk ratio, 0.93; 95% CI, 0.74 to 1.17; P=0.54). Similarly, rates of death at 28 and 90 days were not significantly different in other predefined subgroups, including patients at increased risk for death. Serious bleeding during the treatment period occurred in 10 patients in the DrotAA group and 8 in the placebo group (P=0.81).
Conclusions: DrotAA did not significantly reduce mortality at 28 or 90 days, as compared with placebo, in patients with septic shock. (Funded by Eli Lilly; PROWESS-SHOCK ClinicalTrials.gov number, NCT00604214.).
Source: PubMed