%0 Journal Article %1 vincent_drotrecogin_2005 %A Vincent, Jean-Louis %A Bernard, Gordon R %A Beale, Richard %A Doig, Christopher %A Putensen, Christian %A Dhainaut, Jean-Francois %A Artigas, Antonio %A Fumagalli, Roberto %A Macias, William %A Wright, Theressa %A Wong, Kar %A Sundin, David P %A Turlo, Mary Ann %A Janes, Jonathan %D 2005 %J Critical Care Medicine %K Administration Adult, Aged, Agents, C, Drug Female, Hemorrhages, Humans, Intracranial Male, Middle Outcome Protein Proteins, Rate, Recombinant Schedule, Sepsis, Studies, Survival Treatment {Anti-Infective} {Follow-Up} %N 10 %P 2266--2277 %T 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 %U http://www.ncbi.nlm.nih.gov/pubmed/16215381 %V 33 %X OBJECTIVE: To provide further evidence for the efficacy and safety of drotrecogin alfa (activated) treatment in severe sepsis. DESIGN: Single-arm, open-label, trial of drotrecogin alfa (activated) treatment in severe sepsis patients. Enrollment began in March 2001 and day-28 follow-up completed in January 2003. SETTING: ENHANCE took place in 25 countries at 361 sites. PATIENTS: Patients with known or suspected infection, three or four systemic inflammatory response syndrome criteria, and one or more sepsis-induced organ dysfunctions. Of 2,434 adults entered, 2,378 received drotrecogin alfa (activated), and of these, 2,375 completed the protocol. INTERVENTIONS: Drotrecogin alfa (activated) was infused at a dose of 24 mug/kg/hr for 96 hrs. MEASUREMENTS AND MAIN RESULTS: The 28-day all-cause mortality approximated that observed in PROWESS (25.3\% vs. 24.7\%). Although patients in ENHANCE had increased serious bleeding rates compared with patients in the drotrecogin alfa (activated) arm of PROWESS (during infusion, 3.6\% vs. 2.4\%; postinfusion, 3.2\% vs. 1.2\%; 28-day, 6.5\% vs. 3.5\%), increased postinfusion bleeding suggested a higher background bleeding rate. Intracranial hemorrhage was more common in ENHANCE than PROWESS (during infusion, 0.6\% vs. 0.2\%; 28-day, 1.5\% vs. 0.2\%). The incidence of fatal intracranial hemorrhage was the same during infusion (0.2\%) and higher at 28 days (0.5\% vs. 0.2\%). ENHANCE patients treated within 0-24 hrs from their first sepsis-induced organ dysfunction had lower observed mortality rate than those treated after 24 hrs (22.9\% vs. 27.4\%, p = .01). CONCLUSIONS: ENHANCE provides supportive evidence for the favorable benefit/risk ratio observed in PROWESS and suggests that more effective use of drotrecogin alfa (activated) might be obtained by initiating therapy earlier.

@article{vincent_drotrecogin_2005, abstract = {{OBJECTIVE:} To provide further evidence for the efficacy and safety of drotrecogin alfa (activated) treatment in severe sepsis. {DESIGN:} Single-arm, open-label, trial of drotrecogin alfa (activated) treatment in severe sepsis patients. Enrollment began in March 2001 and day-28 follow-up completed in January 2003. {SETTING:} {ENHANCE} took place in 25 countries at 361 sites. {PATIENTS:} Patients with known or suspected infection, three or four systemic inflammatory response syndrome criteria, and one or more sepsis-induced organ dysfunctions. Of 2,434 adults entered, 2,378 received drotrecogin alfa (activated), and of these, 2,375 completed the protocol. {INTERVENTIONS:} Drotrecogin alfa (activated) was infused at a dose of 24 mug/kg/hr for 96 hrs. {MEASUREMENTS} {AND} {MAIN} {RESULTS:} The 28-day all-cause mortality approximated that observed in {PROWESS} (25.3\% vs. 24.7\%). Although patients in {ENHANCE} had increased serious bleeding rates compared with patients in the drotrecogin alfa (activated) arm of {PROWESS} (during infusion, 3.6\% vs. 2.4\%; postinfusion, 3.2\% vs. 1.2\%; 28-day, 6.5\% vs. 3.5\%), increased postinfusion bleeding suggested a higher background bleeding rate. Intracranial hemorrhage was more common in {ENHANCE} than {PROWESS} (during infusion, 0.6\% vs. 0.2\%; 28-day, 1.5\% vs. 0.2\%). The incidence of fatal intracranial hemorrhage was the same during infusion (0.2\%) and higher at 28 days (0.5\% vs. 0.2\%). {ENHANCE} patients treated within 0-24 hrs from their first sepsis-induced organ dysfunction had lower observed mortality rate than those treated after 24 hrs (22.9\% vs. 27.4\%, p = .01). {CONCLUSIONS:} {ENHANCE} provides supportive evidence for the favorable benefit/risk ratio observed in {PROWESS} and suggests that more effective use of drotrecogin alfa (activated) might be obtained by initiating therapy earlier.}, added-at = {2011-03-11T10:05:34.000+0100}, author = {Vincent, {Jean-Louis} and Bernard, Gordon R and Beale, Richard and Doig, Christopher and Putensen, Christian and Dhainaut, {Jean-Francois} and Artigas, Antonio and Fumagalli, Roberto and Macias, William and Wright, Theressa and Wong, Kar and Sundin, David P and Turlo, Mary Ann and Janes, Jonathan}, biburl = {https://www.bibsonomy.org/bibtex/29c0f94312861d0bf62a3eacc07efa4ae/jelias}, interhash = {203839746a23423a3dc23ab84b6295d5}, intrahash = {9c0f94312861d0bf62a3eacc07efa4ae}, issn = {0090-3493}, journal = {Critical Care Medicine}, keywords = {Administration Adult, Aged, Agents, C, Drug Female, Hemorrhages, Humans, Intracranial Male, Middle Outcome Protein Proteins, Rate, Recombinant Schedule, Sepsis, Studies, Survival Treatment {Anti-Infective} {Follow-Up}}, month = oct, note = {{PMID:} 16215381}, number = 10, pages = {2266--2277}, shorttitle = {Drotrecogin alfa (activated) treatment in severe sepsis from the global open-label trial {ENHANCE}}, timestamp = {2011-03-11T10:05:55.000+0100}, title = {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}, url = {http://www.ncbi.nlm.nih.gov/pubmed/16215381}, volume = 33, year = 2005 }