About: Effect of Eritoran, an Antagonist of MD2-TLR4, on Mortality in Patients With Severe Sepsis The ACCESS Randomized Trial     Goto   Sponge   NotDistinct   Permalink

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  • Importance Eritoran is a synthetic lipid A antagonist that blocks lipopolysaccharide (LPS) from binding at the cell surface MD2-TLR4 receptor. LPS is a major component of the outer membrane of gram-negative bacteria and is a potent activator of the acute inflammatory response. To determine if eritoran, a TLR4 antagonist, would significantly reduce sepsis-induced mortality. We performed a randomized, double-blind, placebo-controlled, multinational phase 3 trial in 197 intensive care units. Patients were enrolled from June 2006 to September 2010 and final follow-up was completed in September 2011. Interventions Patients with severe sepsis (n=1961) were randomized and treated within 12 hours of onset of first organ dysfunction in a 2: 1 ratio with a 6-day course of either eritoran tetrasodium (105 mg total) or placebo, with n=1304 and n=657 patients, respectively. The primary end point was 28-day all-cause mortality. The secondary end points were all-cause mortality at 3, 6, and 12 months after beginning treatment. Baseline characteristics of the 2 study groups were similar. In the modified intent-to-treat analysis (randomized patients who received at least 1 dose) there was no significant difference in the primary end point of 28-day all-cause mortality with 28.1% (366/1304) in the eritoran group vs 26.9% (177/657) in the placebo group (P=.59; hazard ratio, 1.05; 95% CI, 0.88-1.26; difference in mortality rate, -1.1; 95% CI, -5.3 to 3.1) or in the key secondary end point of 1-year all-cause mortality with 44.1% (290/657) in the eritoran group vs 43.3% (565/1304) in the placebo group, Kaplan-Meier analysis of time to death by 1 year, P=.79 (hazard ratio, 0.98; 0.85-1.13). No significant differences were observed in any of the prespecified subgroups. Adverse events, including secondary infection rates, did not differ between study groups. Among patients with severe sepsis, the use of eritoran, compared with placebo, did not result in reduced 28-day mortality.
  • Importance Eritoran is a synthetic lipid A antagonist that blocks lipopolysaccharide (LPS) from binding at the cell surface MD2-TLR4 receptor. LPS is a major component of the outer membrane of gram-negative bacteria and is a potent activator of the acute inflammatory response. To determine if eritoran, a TLR4 antagonist, would significantly reduce sepsis-induced mortality. We performed a randomized, double-blind, placebo-controlled, multinational phase 3 trial in 197 intensive care units. Patients were enrolled from June 2006 to September 2010 and final follow-up was completed in September 2011. Interventions Patients with severe sepsis (n=1961) were randomized and treated within 12 hours of onset of first organ dysfunction in a 2: 1 ratio with a 6-day course of either eritoran tetrasodium (105 mg total) or placebo, with n=1304 and n=657 patients, respectively. The primary end point was 28-day all-cause mortality. The secondary end points were all-cause mortality at 3, 6, and 12 months after beginning treatment. Baseline characteristics of the 2 study groups were similar. In the modified intent-to-treat analysis (randomized patients who received at least 1 dose) there was no significant difference in the primary end point of 28-day all-cause mortality with 28.1% (366/1304) in the eritoran group vs 26.9% (177/657) in the placebo group (P=.59; hazard ratio, 1.05; 95% CI, 0.88-1.26; difference in mortality rate, -1.1; 95% CI, -5.3 to 3.1) or in the key secondary end point of 1-year all-cause mortality with 44.1% (290/657) in the eritoran group vs 43.3% (565/1304) in the placebo group, Kaplan-Meier analysis of time to death by 1 year, P=.79 (hazard ratio, 0.98; 0.85-1.13). No significant differences were observed in any of the prespecified subgroups. Adverse events, including secondary infection rates, did not differ between study groups. Among patients with severe sepsis, the use of eritoran, compared with placebo, did not result in reduced 28-day mortality. (en)
Title
  • Effect of Eritoran, an Antagonist of MD2-TLR4, on Mortality in Patients With Severe Sepsis The ACCESS Randomized Trial
  • Effect of Eritoran, an Antagonist of MD2-TLR4, on Mortality in Patients With Severe Sepsis The ACCESS Randomized Trial (en)
skos:prefLabel
  • Effect of Eritoran, an Antagonist of MD2-TLR4, on Mortality in Patients With Severe Sepsis The ACCESS Randomized Trial
  • Effect of Eritoran, an Antagonist of MD2-TLR4, on Mortality in Patients With Severe Sepsis The ACCESS Randomized Trial (en)
skos:notation
  • RIV/00216208:11120/13:43907680!RIV14-MSM-11120___
http://linked.open...avai/riv/aktivita
http://linked.open...avai/riv/aktivity
  • N
http://linked.open...iv/cisloPeriodika
  • 11
http://linked.open...vai/riv/dodaniDat
http://linked.open...aciTvurceVysledku
http://linked.open.../riv/druhVysledku
http://linked.open...iv/duvernostUdaju
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  • 71489
http://linked.open...ai/riv/idVysledku
  • RIV/00216208:11120/13:43907680
http://linked.open...riv/jazykVysledku
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  • lipopolysaccharide; receptor 4; tetrasodium e5564; endotoxin response; septic shock; gram-negative bacteremia (en)
http://linked.open.../riv/klicoveSlovo
http://linked.open...odStatuVydavatele
  • US - Spojené státy americké
http://linked.open...ontrolniKodProRIV
  • [CF63A7A9284F]
http://linked.open...i/riv/nazevZdroje
  • JAMA-Journal of the American Medical Association
http://linked.open...in/vavai/riv/obor
http://linked.open...ichTvurcuVysledku
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http://linked.open...UplatneniVysledku
http://linked.open...v/svazekPeriodika
  • 309
http://linked.open...iv/tvurceVysledku
  • Pachl, Jan
http://linked.open...ain/vavai/riv/wos
  • 000316276500029
issn
  • 0098-7484
number of pages
http://bibframe.org/vocab/doi
  • 10.1001/jama.2013.2194
http://localhost/t...ganizacniJednotka
  • 11120
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