Recombinant human activated protein C, or rhAPC for the treatment of sepsis.
The relative risk of death among patients receiving this drug for sepsis is 19.4% lower than that of patients receiving placebo.
Activated protein C effects in sepsis include anticoagulation, inhibition of systemic inflammation, inhibits nitric oxide vascular dysfunction, apoptosis of lymphocytes, and endothelium, and activates neutrophils.
ENHANCE trial suggested a higher rate of bleeding than initial study in the PROWESS study with 6.5% incidence of serious bleeding in a 28 day period.
If bleeding occurs the therapy should be stopped immediately.
The drug half-life is only 15 minutes.
Its use in sepsis results is dose dependent reductions in D-dimer and interleukin 6 levels without an increase in serious bleeding events.
PROWESS study- Prospective Recombinant Human Activated Protein C Worldwide Evaluation In Severe Sepsis- utilized 24 mcg per kilogram of body weight per hour in a placebo-controlled, randomized, double-blind, multicenter trial of 690 patients, and approximately 75% of patients had multi-organ dysfunction: mortality rate was 24.7% at 28 days compared to 30.8% for placebo patients.
Associated with an increased risk of bleeding in 3.5% of patients taking the drug, versus 2.0% of those taking placebo (PROWESS).
Most benefits of the drug is seen in patients at increased risk for death, i.e. patients with severe sepsis.
The Administration of Drotrecogin Alfa in Early Stage Severe Sepsis(ADDRESS) trial evaluated the use of this agent in patients with severe sepsis
In general, no dose adjustments on the basis of laboratory values are made during the 96 hour infusion.
Standard clotting tests and platelet counts are monitored to identify increased risk of bleeding.
In a 28 day study serious bleeding was observed in 3.5 to 6.5% patients receiving the agent as compared with 2 to 5% of patients receiving placebo, and CNS bleeding occurred in 0 to 1.5% of patients with this drug is compared with 0.7% with placebo (Lat2242e PF).
Minor increases in prothrombin time or decreases in the D-dimer are not reasons to adjust the treatment in the absence of clinical bleeding.
In the presence of severe bleeding the drug infusion should be stopped, and not restarted.
Withdrawn from the market October 25, 2011.
In the Administration of Drotrecogin Alfa in Early Stage Severe Sepsis (ADDRESS) trial associated with either a single organ failure or APACHE II score below 25:. The 28 day rate of death from any cause was 18.5% for this agent and 17% in the placebo group, which terminated the study, because there was no indication of a positive effect(Abraham E). 10