CURB-65, PSI, and APACHE II to assess mortality risk in patients with severe sepsis and community acquired pneumonia in PROWESS.

Background: Patients with community-acquired pneumonia (CAP) comprised 35.6% of the overall phase 3 Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) study and 33.1% of the placebo arm.

Static and dynamic assessment of biomarkers in surgical patients with severe sepsis.

Background: Severe sepsis, defined as a systemic inflammatory response to infection associated with acute organ dysfunction, is common among surgical patients and is a major cause of morbidity and mortality. Severe sepsis has been associated with changes in inflammatory and hemostatic biomarkers. In patients undergoing surgical procedures there may be additional stimulation of cytokine release and activation of the coagulation system.

Safety of drotrecogin alfa (activated) in surgical patients with severe sepsis.

Background: We conducted a retrospective evaluation of the overall safety of drotrecogin alfa (activated) in surgical patients with severe sepsis enrolled in PROWESS.

Methods: A blinded Surgical Evaluation Committee (SEC) verified surgical patients as having undergone a significant operative procedure within 30 days prior to enrollment. Serious and treatment-emergent bleeding events, both during the study drug infusion period (120 h) and the entire 28-day study period were analyzed by surgical status and by treatment assignment.

Benefit/risk profile of drotrecogin alfa (activated) in surgical patients with severe sepsis.

Background: The Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) trial examined the safety and efficacy of drotrecogin alfa (activated) (Xigris) in adult patients with severe sepsis. A clinical evaluation committee examined clinical data for each patient enrolled in PROWESS. However, there were no surgeons on the committee, and thus questions remained regarding the safety and efficacy of drotrecogin alfa (activated) in surgical patients.

Safety, pharmacokinetics, and pharmacodynamics of drotrecogin alfa (activated) in children with severe sepsis.

Objective: In a phase 3 trial, recombinant human activated protein C (drotrecogin alfa [activated]) significantly reduced mortality in adult patients with severe sepsis. We have now performed a preliminary analysis of the safety, pharmacokinetics, and pharmacodynamics of drotrecogin alfa (activated) in pediatric patients with severe sepsis.

Design And Setting: Open-label, nonrandomized, sequential, 2-part study conducted in 11 medical centers in the United States and United Kingdom.

The clinical evaluation committee in a large multicenter phase 3 trial of drotrecogin alfa (activated) in patients with severe sepsis (PROWESS): role, methodology, and results.

Objective: In the multinational PROWESS trial, drotrecogin alfa (activated) significantly reduced mortality rate in patients with severe sepsis compared with placebo. The use of large multiple-center trials can potentially complicate interpretation of results in severe sepsis populations because of variability in medical attitudes and practices and the frequency of confounding events such as protocol violations. The objective of this study was to perform a blinded, critical, integrated review of data from the 1,690 severe sepsis patients from 164 medical centers enrolled in the PROWESS trial using a Clinical Evaluation Committee.