What is the role of activated protein C therapy in the management of multiple organ dysfunction syndrome (MODS) in sepsis?

Updated: Jan 27, 2020
  • Author: Ali H Al-Khafaji, MD, MPH; Chief Editor: Michael R Pinsky, MD, CM, Dr(HC), FCCP, FAPS, MCCM  more...
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Answer

Activated protein C is an endogenous protein that not only promotes fibrinolysis and inhibits thrombosis and inflammation but also may modulate the coagulation and inflammation of severe sepsis. Sepsis reduces the level of protein C and inhibits conversion of protein C to activated protein C. Administration of recombinant activated protein C inhibits thrombosis and inflammation, promotes fibrinolysis, and modulates coagulation and inflammation.

An early publication by the Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) study group demonstrated that administration of recombinant human activated protein C (drotrecogin alfa) resulted in lower mortality (24.7%) in the treatment group than in the placebo group (30.8%). [24] Treatment with drotrecogin alfa was associated with a 19.4% relative reduction in the risk of death and a 6.1% absolute reduction in the risk of death.

After that early publication, the efficacy and safety of drotrecogin alfa were widely debated. Drotrecogin alfa was withdrawn from the worldwide market on October 25, 2011, after analysis of the PROWESS-SHOCK clinical trial, in which the drug failed to demonstrate a statistically significant reduction in 28-day all-cause mortality in patients with severe sepsis and septic shock. [25] Trial results observed a 28-day all-cause mortality of 26.4% in patients treated with drotrecogin alfa, compared with 24.2% in the placebo group.


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