Document Detail


A retrospective observational study of drotrecogin alfa (activated) in adults with severe sepsis: comparison with a controlled clinical trial.
MedLine Citation:
PMID:  18158435     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: To compare characteristics and outcomes of patients treated with drotrecogin alfa (activated) (DrotAA) in clinical practice to those treated in a phase III randomized controlled trial (PROWESS). DESIGN: Observational data were collected retrospectively from patients who received DrotAA as part of physician-directed treatment. SETTING: Intensive care units of five teaching institutions. PATIENTS: Patients were > or = 18 yrs old, had severe sepsis (confirmed/suspected infection with one or more sepsis-induced organ dysfunctions), and received DrotAA. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Baseline demographics, severity of illness, time from organ dysfunction onset to DrotAA treatment, daily assessment of organ dysfunction, serious bleeding events, and in-hospital mortality were reported. Timing from severe sepsis documentation to start of DrotAA infusion was categorized: day 0 (same calendar day); day 1 (next calendar day); and day > or = 2 (second calendar day or later). Clinical practice patients (n = 274) were younger, had more comorbidities, had higher severity of illness (as measured by organ dysfunction or greater vasopressor/ventilator use), and received DrotAA later than PROWESS patients (all p < .05). Overall hospital mortality for clinical practice patients was 42%, compared with 37% for DrotAA-treated PROWESS patients with Acute Physiology and Chronic Health Evaluation II score > or = 25. Mortality for day 0, day 1, and day > or = 2 groups was 33%, 40%, and 52%, respectively. In PROWESS, the vast majority were treated on day 0 or day 1. Serious bleeding events during infusion were noted in 4.0% of clinical practice patients compared with 2.2% of PROWESS DrotAA-treated patients with Acute Physiology and Chronic Health Evaluation II score > or = 25. CONCLUSIONS: Patients treated in clinical practice differed from those in PROWESS. Patients were younger, had more comorbidities, had greater severity of illness, and had longer mean time from severe sepsis onset to the start of DrotAA. Hospital mortality for patients treated within 1 day of severe sepsis onset was similar to DrotAA-treated PROWESS patients. While the low number of serious bleeding events precludes a definitive assessment, the observed incidence of serious bleeding events in clinical practice patients was numerically higher than in DrotAA-treated PROWESS patients.
Authors:
Arthur Wheeler; Jay Steingrub; Gregory A Schmidt; Philip Sanchez; Judith Jacobi; Walter Linde-Zwirble; Becky Bates; Rebecca L Qualy; Brad Woodward; Michael Zeckel
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Publication Detail:
Type:  Comparative Study; Journal Article; Multicenter Study; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Critical care medicine     Volume:  36     ISSN:  1530-0293     ISO Abbreviation:  Crit. Care Med.     Publication Date:  2008 Jan 
Date Detail:
Created Date:  2007-12-25     Completed Date:  2008-02-12     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0355501     Medline TA:  Crit Care Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  14-23     Citation Subset:  AIM; IM    
Affiliation:
Vanderbilt Medical Center, Nashville, TN, USA. art.wheeler@vanderbilt.edu
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MeSH Terms
Descriptor/Qualifier:
APACHE
Adult
African Americans / statistics & numerical data
Age Distribution
Anti-Infective Agents / therapeutic use*
Cardiomyopathies / epidemiology
Clinical Trials, Phase III as Topic
Comorbidity
Female
Hemorrhage / epidemiology
Hospital Mortality
Humans
Liver Diseases / epidemiology
Male
Middle Aged
Neoplasms / epidemiology
Observation
Professional Practice / statistics & numerical data*
Protein C / therapeutic use*
Recombinant Proteins / therapeutic use
Retrospective Studies
Sepsis / drug therapy*,  epidemiology*
United States / epidemiology
Chemical
Reg. No./Substance:
0/Anti-Infective Agents; 0/Protein C; 0/Recombinant Proteins; 0/drotrecogin alfa activated
Comments/Corrections
Comment In:
Crit Care Med. 2008 Jan;36(1):332-3   [PMID:  18158441 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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