Drotrecogin alfa (activated).

Abstract:

:Drotrecogin alfa (activated), recombinant human activated protein C, inhibits coagulation and inflammation and promotes fibrinolysis in patients with severe sepsis. 850 patients with severe sepsis treated with intravenous drotrecogin alfa (activated) 24 microg/kg/h for 96 hours had a significantly greater reduction in 28-day all-cause mortality (24.7%) than 840 placebo recipients (30.8%) in a randomised, double-blind, placebo-controlled study. The drug was associated with a 19.4% reduction in the relative risk of death at 28 days compared with placebo. Baseline characteristics of and pre-existing conditions in patients with sepsis appeared to have no effect on the efficacy of drotrecogin alfa (activated). A significantly greater reduction in median percentage change from baseline plasma D-dimer levels (a coagulation marker) was seen with drotrecogin alfa (activated) treatment than with placebo on study days 1 to 7 in patients with severe sepsis. On study days 1, 4, 5, 6 and 7, a significantly greater median reduction in interleukin-6 levels (an inflammation marker) from baseline was seen with drotrecogin alfa (activated) treatment than placebo. Drotrecogin alfa (activated) was associated with an increased incidence of serious bleeding events during the infusion period [2.4% vs 1.0% with placebo; p = 0.024] and the 28-day study period (3.5 vs 2.0%; p = 0.06) of the efficacy trial. This increase was primarily related to procedure-related events; there were no significant differences between the treatment groups in nonprocedure-related serious bleeding events. The most frequent site of bleeding was the gastrointestinal tract. With the exception of bleeding events, there were no clinically significant differences between treatment groups in the efficacy trial in the incidence of adverse events. Of the 210 deaths in patients with severe sepsis treated with drotrecogin alfa (activated) 24 microg/kg/h in the efficacy trial, four deaths due to haemorrhage and one due to cerebral oedema were possibly related to the study drug.

journal_name

Drugs

journal_title

Drugs

authors

Lyseng-Williamson KA,Perry CM

doi

10.2165/00003495-200262040-00006

subject

Has Abstract

pub_date

2002-01-01 00:00:00

pages

617-30; discussion 631-2

issue

4

eissn

0012-6667

issn

1179-1950

pii

620406

journal_volume

62

pub_type

临床试验,杂志文章,随机对照试验

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