Hospital mortality and resource use in subgroups of the Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) trial

Crit Care Med. 2004 Nov;32(11):2207-18. doi: 10.1097/01.ccm.0000145231.71605.d8.

Abstract

Objective: To compare differences in hospital mortality and resource use in adult severe sepsis subjects randomized to receive drotrecogin alfa (activated) (DrotAA) or placebo in the PROWESS trial.

Design: Retrospective, cross-sectional, blinded follow-up of subjects enrolled in a previous randomized, controlled trial.

Setting: One hundred sixty-four tertiary care institutions in 11 countries.

Participants: The 1,690 subjects with severe sepsis enrolled and treated with study drug in PROWESS, of whom 1,220 were alive at 28 days (the end of the original PROWESS follow-up).

Interventions: DrotAA (n = 850), 24 microg/kg/hr for 96 hrs, or placebo (n = 840).

Measurements and main results: New follow-up data through hospital discharge were merged with existing 28-day follow-up data. Hospital mortality was calculated for designated subgroups. Intensive care unit and hospital length of stay and Simplified Therapeutic Intervention Scoring System-28 (TISS-28) scores were calculated overall and in designated subgroups. Hospital discharge location was recorded. The 95% confidence interval of most subgroups contained the relative risk estimate for overall 28-day and hospital mortality. Median hospital length of stay and intensive care unit length of stay were similar in both treatment groups: 16 vs. 17 days (p = .22) and 9 vs. 9 days (p = .7) for placebo vs. DrotAA. No significant difference in TISS-28 scores was observed between treatment groups overall or in subgroups of disease severity. In subjects for whom discharge destination was reported, 42.8% of placebo subjects and 46.8% of DrotAA subjects (two thirds of survivors in each group) were discharged directly to home.

Conclusions: Reduction in hospital mortality with DrotAA in most of the subgroups of PROWESS is consistent with the reduction in 28-day and hospital mortality observed in the overall PROWESS population. Additional survivors created with DrotAA treatment did not increase per-patient resource use or intensive care unit or hospital length of stay.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • APACHE
  • Activities of Daily Living
  • Aged
  • Anti-Infective Agents / pharmacology
  • Anti-Infective Agents / therapeutic use*
  • Bacterial Infections / complications
  • Bacterial Infections / drug therapy
  • Bacterial Infections / mortality
  • Cross-Sectional Studies
  • Female
  • Follow-Up Studies
  • Health Resources / statistics & numerical data*
  • Hospital Mortality*
  • Humans
  • Infusions, Intravenous
  • Intensive Care Units / statistics & numerical data
  • Length of Stay / statistics & numerical data
  • Male
  • Middle Aged
  • Multiple Organ Failure / microbiology
  • Patient Discharge / statistics & numerical data
  • Patient Selection
  • Protein C / pharmacology
  • Protein C / therapeutic use*
  • Recombinant Proteins / pharmacology
  • Recombinant Proteins / therapeutic use*
  • Retrospective Studies
  • Risk Factors
  • Sepsis / complications
  • Sepsis / drug therapy*
  • Sepsis / mortality*
  • Survival Analysis
  • Treatment Outcome

Substances

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