Drotrecogin alfa (activated) (recombinant human activated protein C) for the treatment of severe sepsis.

Abstract

OBJECTIVE:

To review the data supporting drotrecogin alfa (activated) for severe sepsis treatment.

DATA SOURCES:

Published research and data from the Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) trial.

DATA EXTRACTION AND SYNTHESIS:

The coagulation cascade and intense inflammation play a central role in the development of organ failure due to severe sepsis. Drotrecogin alfa (activated) has anti-inflammatory, antithrombotic, profibrinolytic, and other properties that may explain the beneficial results seen in both animal models and humans with severe sepsis. Drotrecogin alfa (activated) produces a robust reduction in the mortality rate of patients with severe sepsis that is evident across nearly every subgroup examined in the phase III clinical trial and has an acceptable safety profile with bleeding during infusion as the only significant risk associated with therapy. The relative risk reductions for mortality seen in Gram-negative, Gram-positive, pneumonia, abdominal sources, shock, and nonshock are similar to the intent-to-treat population, 19.4%. Treatment also increases days alive and free from mechanical ventilation and shock.

CONCLUSIONS:

Coagulopathy and systemic inflammation are almost universal in patients with severe sepsis. Treatment of this disorder with drotrecogin alfa (activated) directly addresses these derangements and substantially reduces morbidity and mortality rates with potential for bleeding during infusion as the only known risk.

• Authors: Gordon R Bernard
• Journal: Critical care medicine (Crit Care Med) Vol. 31 Issue 1 Suppl Pg. S85-93 (Jan 2003) ISSN: 0090-3493 [Print] United States
• PMID: 12544981 (Publication Type: Clinical Trial, Journal Article, Randomized Controlled Trial, Review)

Chemical References

• Anti-Infective Agents
• Protein C
• Recombinant Proteins
• drotrecogin alfa activated

Topics

• Animals
• Anti-Infective Agents (pharmacokinetics, therapeutic use)
• Clinical Trials, Phase II as Topic
• Clinical Trials, Phase III as Topic
• Disease Models, Animal
• Drug Approval
• Humans
• Protein C (pharmacokinetics, therapeutic use)
• Rats
• Recombinant Proteins (pharmacokinetics, therapeutic use)
• Sepsis (drug therapy, mortality)
• Severity of Illness Index
• Survival Rate