Drotrecogin alfa (activated) in patients with severe sepsis presenting with purpura fulminans, meningitis, or meningococcal disease: a retrospective analysis of patients enrolled in recent clinical studies.

Abstract

INTRODUCTION:

We report data from adult and pediatric patients with severe sepsis from studies evaluating drotrecogin alfa (activated) (DrotAA) and presenting with purpura fulminans (PF), meningitis (MEN), or meningococcal disease (MD) (PF/MEN/MD). Such conditions may be associated with an increased bleeding risk but occur in a relatively small proportion of patients presenting with severe sepsis; pooling data across clinical trials provides an opportunity for improving the characterization of outcomes.

METHODS:

A retrospective analysis of placebo-controlled, open-label, and compassionate-use trials was conducted. Adult patients received infusions of either DrotAA or placebo. All pediatric patients (<18 years old) received DrotAA. 189 adult and 121 pediatric patients presented with PF/MEN/MD.

RESULTS:

Fewer adult patients with PF/MEN/MD met cardiovascular (68.3% versus 78.8%) or respiratory (57.8% versus 80.5%) organ dysfunction entry criteria than those without. DrotAA-treated adult patients with PF/MEN/MD (n = 163) had an observed 28-day mortality rate of 19.0%, a 28-day serious bleeding event (SBE) rate of 6.1%, and an intracranial hemorrhage (ICH) rate of 4.3%. Six of the seven ICHs occurred in patients with MEN (three of whom were more than 65 years old with a history of hypertension). DrotAA-treated adult patients without PF/MEN/MD (n = 3,088) had an observed 28-day mortality rate of 25.5%, a 28-day SBE rate of 5.8%, and an ICH rate of 1.0%. In contrast, a greater number of pediatric patients with PF/MEN/MD met the cardiovascular organ dysfunction entry criterion (93.5% versus 82.5%) than those without. DrotAA-treated PF/MEN/MD pediatric patients (n = 119) had a 14-day mortality rate of 10.1%, an SBE rate of 5.9%, and an ICH rate of 2.5%. DrotAA-treated pediatric patients without PF/MEN/MD (n = 142) had a 14-day mortality rate of 14.1%, an SBE rate of 9.2%, and an ICH rate of 3.5%.

CONCLUSION:

DrotAA-treated adult patients with severe sepsis presenting with PF/MEN/MD had a similar SBE rate, a lower observed 28-day mortality rate, and a higher observed rate of ICH than DrotAA-treated patients without PF/MEN/MD. DrotAA-treated pediatric patients with severe sepsis with PF/MEN/MD may differ from adults, because all three outcome rates (SBE, mortality, and ICH) were lower in pediatric patients with PF/MEN/MD.

• Authors: Jean-Louis Vincent, Simon Nadel, Demetrios J Kutsogiannis, R T Noel Gibney, S Betty Yan, Virginia L Wyss, Joan E Bailey, Carol L Mitchell, Samiha Sarwat, Stephen M Shinall, Jonathan M Janes
• Journal: Critical care (London, England) (Crit Care) Vol. 9 Issue 4 Pg. R331-43 (Aug 2005) ISSN: 1466-609X [Electronic] England
• PMID: 16137345 (Publication Type: Comparative Study, Journal Article)

Chemical References

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

Topics

• Adult
• Aged
• Anti-Infective Agents (therapeutic use)
• Child
• Child, Preschool
• Comorbidity
• Female
• Hemorrhage (epidemiology)
• Humans
• IgA Vasculitis (epidemiology)
• Intracranial Hemorrhages (epidemiology)
• Male
• Meningitis, Bacterial (epidemiology)
• Meningococcal Infections (epidemiology)
• Middle Aged
• Odds Ratio
• Protein C (therapeutic use)
• Recombinant Proteins (therapeutic use)
• Retrospective Studies
• Sepsis (drug therapy, epidemiology)
• Survival Analysis
• Treatment Outcome