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

Jean-Louis Vincent¹ , Simon Nadel² , Demetrios J Kutsogiannis³ , RT Noel Gibney⁴ , S Betty Yan⁵ , Virginia L Wyss⁶ , Joan E Bailey⁷ , Carol L Mitchell⁸ , Samiha Sarwat⁹ , Stephen M Shinall¹⁰ and Jonathan M Janes¹¹

¹Head, Department of Intensive Care, University of Brussels (Erasme Hospital), Brussels, Belgium

²Consultant in Paediatric Intensive Care, Department of Paediatrics, Imperial College London (St. Mary's Hospital), London, UK

³Assistant Professor, Department of Public Health Sciences, Division of Critical Care Medicine, University of Alberta (Royal Alexandra Hospital), Edmonton, Alberta, Canada

⁴Professor, Division of Critical Care Medicine, University of Alberta (University of Alberta Hospital), Edmonton, Alberta, Canada

⁵Research Fellow, Lilly Research Laboratories, Indianapolis, IN, USA

⁶Associate Consultant, Project Management, Lilly Research Laboratories, Indianapolis, IN, USA

⁷Clinical Development Associate, Lilly Research Laboratories, Indianapolis, IN, USA

⁸Associate Global Medical Information Consultant, Lilly Research Laboratories, Indianapolis, IN, USA

⁹Statistician, Lilly Research Laboratories, Indianapolis, IN, USA

¹⁰Scientific Communications Associate, Lilly Research Laboratories, Indianapolis, IN, USA

¹¹Medical Advisor, Lilly Research Centre, Erl Wood Manor, Windlesham, Surrey, UK

author email corresponding author email

Critical Care 2005, 9:R331-R343doi:10.1186/cc3538


Published:	17 May 2005

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.