Effectiveness and safety of drotrecogin alfa (activated) for severe sepsis: a meta-analysis and metaregression

Summary Background Drotrecogin alfa (activated) was approved for use in severe sepsis in 2001 on the basis of the Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) trial, but controversies about its effectiveness remain. We aimed to assess effectiveness and safety...

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Bibliographic Details
Published in:The Lancet infectious diseases 2012-09, Vol.12 (9), p.678-686
Main Authors: Kalil, Andre C, Dr, LaRosa, Steven P, MD
Format: Article
Language:English
Subjects:
activated protein C
Adult
Aged
Anti-Infective Agents - administration & dosage
Anti-Infective Agents - adverse effects
Bacterial diseases
Bacterial sepsis
Biological and medical sciences
Bleeding
Drug-Related Side Effects and Adverse Reactions - epidemiology
Drugs
Female
Hemorrhage - chemically induced
Hemorrhage - epidemiology
Heterogeneity
Human bacterial diseases
Humans
Infectious Disease
Infectious diseases
Male
Medical sciences
Middle Aged
Mortality
Protein C - administration & dosage
Protein C - adverse effects
Recombinant Proteins - administration & dosage
Recombinant Proteins - adverse effects
Reviews
Safety
Sepsis
Sepsis - drug therapy
Survival Analysis
Treatment Outcome
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Summary:Summary Background Drotrecogin alfa (activated) was approved for use in severe sepsis in 2001 on the basis of the Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) trial, but controversies about its effectiveness remain. We aimed to assess effectiveness and safety of use of this drug in the past 10 years and compare them with the original PROWESS results. Methods We searched PubMed, Embase, Ovid, Cochrane Library, Evidence-Based Medicine , and the American College of Physicians Journal Club databases for experimental and analytical studies of drotrecogin alfa (activated) in adults with severe sepsis until Jan 31, 2012. We calculated adjusted risk ratios for effectiveness and safety outcomes with random-effects models. We did a metaregression to assess the effect of severity of illness on the risk of death and the risk of bleeding associated with drotrecogin alfa (activated). Findings We included nine controlled trials (41 401 patients) and 16 single-group studies (5822 patients) in effectiveness analyses and 20 studies (8245 patients) in safety analyses. Hospital mortality was reduced by 18% with drotrecogin alfa (activated) compared with controls (relative risk 0·822, 95% CI 0·779–0·867; p
ISSN:1473-3099
1474-4457
DOI:10.1016/S1473-3099(12)70157-3