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Clinical trials in severe sepsis with drotrecogin alfa (activated).

Laterre PF - Crit Care (2007)

Bottom Line: Drotecogin alfa (activated; DrotAA) was approved in 2001 by the US Food and Drug Administration for the treatment of patients with severe sepsis who are at high risk for death.The European Agency for the Evaluation of Medical Products also recommended that DrotAA could be administered to patients with severe sepsis and multiple organ dysfunction when added to the best standard care.Following the initial publication of the PROWESS (Protein C Worldwide Evaluation in Severe Sepsis) findings, multiple subgroup analyses supported the need for additional studies to explore the various hypotheses raised by this study.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Critical Care Medicine, St-Luc University Hospital, Université Catholique de Louvain, Avenue Hippocrate, 1200 Brussels, Belgium. laterre@rean.ucl.ac.be

ABSTRACT
Drotecogin alfa (activated; DrotAA) was approved in 2001 by the US Food and Drug Administration for the treatment of patients with severe sepsis who are at high risk for death. The European Agency for the Evaluation of Medical Products also recommended that DrotAA could be administered to patients with severe sepsis and multiple organ dysfunction when added to the best standard care. Following the initial publication of the PROWESS (Protein C Worldwide Evaluation in Severe Sepsis) findings, multiple subgroup analyses supported the need for additional studies to explore the various hypotheses raised by this study. This review discusses all large clinical trials exploring the efficacy and safety of DrotAA and proposes recommendations for the use of DrotAA in severe sepsis.

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Related in: MedlinePlus

Kaplan-Meier survival curves. Comparison of ENHANCE (Extended Evaluation of Recombinant Human Activated Protein C) 28-day survival with that of PROWESS (Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis). DrotAA, drotecogin alfa (activated). Reproduced with permission from Vincent JL, Bernard GR, Beale R, Doig C, Putensen C, Dhainaut JF, Artigas A, Fumagalli R, Macias W, Wright T, Wong K, Sundin DP, Turlo MA, Janes J: Drotrecogin alfa (activated) treatment in severe sepsis from the global open-label trial ENHANCE: further evidence for survival and safety and implications for early treatment. Crit Care Med 2005, 33:2266–2277.
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Figure 1: Kaplan-Meier survival curves. Comparison of ENHANCE (Extended Evaluation of Recombinant Human Activated Protein C) 28-day survival with that of PROWESS (Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis). DrotAA, drotecogin alfa (activated). Reproduced with permission from Vincent JL, Bernard GR, Beale R, Doig C, Putensen C, Dhainaut JF, Artigas A, Fumagalli R, Macias W, Wright T, Wong K, Sundin DP, Turlo MA, Janes J: Drotrecogin alfa (activated) treatment in severe sepsis from the global open-label trial ENHANCE: further evidence for survival and safety and implications for early treatment. Crit Care Med 2005, 33:2266–2277.

Mentions: The only major difference with PROWESS regarding the inclusion criteria was the time window for intervention. In ENHANCE, DrotAA infusion could be initiated up to 48 hours after the first sepsis-induced organ dysfunction. A total of 2,378 patients received DrotAA in this study. Baseline characteristics revealed that the enrolled population was more severely ill than in the PROWESS population. More patients required vasopressors and mechanical ventilation, they had a higher mean Sequential Organ Failure Assessment score, and they had undergone surgery before enrolment. Therefore, the observed 28-day, all-cause mortality of 25.3%, similar to that in PROWESS, was the main reassuring result in terms of efficacy. The Kaplan-Meier survival curve of ENHANCE was almost superimposable on that of the DrotAA-treated arm of PROWESS (Figure 1).


Clinical trials in severe sepsis with drotrecogin alfa (activated).

Laterre PF - Crit Care (2007)

Kaplan-Meier survival curves. Comparison of ENHANCE (Extended Evaluation of Recombinant Human Activated Protein C) 28-day survival with that of PROWESS (Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis). DrotAA, drotecogin alfa (activated). Reproduced with permission from Vincent JL, Bernard GR, Beale R, Doig C, Putensen C, Dhainaut JF, Artigas A, Fumagalli R, Macias W, Wright T, Wong K, Sundin DP, Turlo MA, Janes J: Drotrecogin alfa (activated) treatment in severe sepsis from the global open-label trial ENHANCE: further evidence for survival and safety and implications for early treatment. Crit Care Med 2005, 33:2266–2277.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2230609&req=5

Figure 1: Kaplan-Meier survival curves. Comparison of ENHANCE (Extended Evaluation of Recombinant Human Activated Protein C) 28-day survival with that of PROWESS (Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis). DrotAA, drotecogin alfa (activated). Reproduced with permission from Vincent JL, Bernard GR, Beale R, Doig C, Putensen C, Dhainaut JF, Artigas A, Fumagalli R, Macias W, Wright T, Wong K, Sundin DP, Turlo MA, Janes J: Drotrecogin alfa (activated) treatment in severe sepsis from the global open-label trial ENHANCE: further evidence for survival and safety and implications for early treatment. Crit Care Med 2005, 33:2266–2277.
Mentions: The only major difference with PROWESS regarding the inclusion criteria was the time window for intervention. In ENHANCE, DrotAA infusion could be initiated up to 48 hours after the first sepsis-induced organ dysfunction. A total of 2,378 patients received DrotAA in this study. Baseline characteristics revealed that the enrolled population was more severely ill than in the PROWESS population. More patients required vasopressors and mechanical ventilation, they had a higher mean Sequential Organ Failure Assessment score, and they had undergone surgery before enrolment. Therefore, the observed 28-day, all-cause mortality of 25.3%, similar to that in PROWESS, was the main reassuring result in terms of efficacy. The Kaplan-Meier survival curve of ENHANCE was almost superimposable on that of the DrotAA-treated arm of PROWESS (Figure 1).

Bottom Line: Drotecogin alfa (activated; DrotAA) was approved in 2001 by the US Food and Drug Administration for the treatment of patients with severe sepsis who are at high risk for death.The European Agency for the Evaluation of Medical Products also recommended that DrotAA could be administered to patients with severe sepsis and multiple organ dysfunction when added to the best standard care.Following the initial publication of the PROWESS (Protein C Worldwide Evaluation in Severe Sepsis) findings, multiple subgroup analyses supported the need for additional studies to explore the various hypotheses raised by this study.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Critical Care Medicine, St-Luc University Hospital, Université Catholique de Louvain, Avenue Hippocrate, 1200 Brussels, Belgium. laterre@rean.ucl.ac.be

ABSTRACT
Drotecogin alfa (activated; DrotAA) was approved in 2001 by the US Food and Drug Administration for the treatment of patients with severe sepsis who are at high risk for death. The European Agency for the Evaluation of Medical Products also recommended that DrotAA could be administered to patients with severe sepsis and multiple organ dysfunction when added to the best standard care. Following the initial publication of the PROWESS (Protein C Worldwide Evaluation in Severe Sepsis) findings, multiple subgroup analyses supported the need for additional studies to explore the various hypotheses raised by this study. This review discusses all large clinical trials exploring the efficacy and safety of DrotAA and proposes recommendations for the use of DrotAA in severe sepsis.

Show MeSH
Related in: MedlinePlus