ReviewCritical care (London, England)2006
Drotrecogin alfa (activated): does current evidence support treatment for any patients with severe sepsis?
Review in Critical care (London, England), 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
12 citing papers in PubMed, 41 citations in OpenAlex.
- Antagonism of alpha2A-adrenoceptor: a novel approach to inhibit inflammatory responses in sepsis.Journal of molecular medicine (Berlin, Germany) · 2010Article
- Design, conduct, analysis and reporting of a multi-national placebo-controlled trial of activated protein C for persistent septic shock.Intensive care medicine · 2008Article
- Activated protein C in sepsis: the promise of nonanticoagulant activated protein C.Current opinion in hematology · 2008Review
- Is There NO Treatment For Severe Sepsis?The Libyan journal of medicine · 2008Article
- Effect of sepsis therapies on health-related quality of life.Critical care (London, England) · 2008Article
- Drotrecogin alfa (activated) in severe sepsis: a systematic review and new cost-effectiveness analysis.BMC anesthesiology · 2007Article
- Benefit-risk assessment of drotrecogin alfa (activated) in the treatment of sepsis.Drug safety · 2007Review
- Drotrecogin alfa (activated) in patients with severe sepsis and a high risk of death.Critical care (London, England) · 2006Article
- Drotrecogin alfa (activated): current evidence supports treatment for severe sepsis patients with a high risk of death.Critical care (London, England) · 2006Article
- Drotrecogin alfa (activated): down and not out, but not really in either.Critical care (London, England) · 2006Article
- Patience and change: a conflict of interests?Critical care (London, England) · 2006Article
- Activated protein C in sepsis: down but not out, yet.Critical care (London, England) · 2006Article
Corrections and comments
- Commented on by
- Commented on by
- Commented on by
Authors and funding
3 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Two international multicentre randomised controlled trials of drotrecogin alfa (activated) (DrotAA), the Recombinant Human Activated Protein C Worldwide Evaluation of Severe Sepsis (PROWESS) and Administration of Drotrecogin Alfa (Activated) in Early Stage Severe Sepsis (ADDRESS) trials, have produced inconsistent results. When 28-day mortality data from these trials for patients with severe sepsis and at high risk of death are pooled using a standard random-effects meta-analysis technique, there is no statistically significant survival benefit (for patients with Acute Physiology and Chronic Health Evaluation (APACHE II) scores of 25 or more), or a borderline significant benefit (for patients with multi-organ failure). We argue that two important methodological issues might explain the disparate results between the two trials. These issues centre on early trial stopping, which exaggerates treatment effects, and reliance on subgroup analyses, which for DrotAA yields inconsistent results across different definitions of high risk. These concerns call into question the effectiveness of DrotAA in any patients with severe sepsis. Consequently, further randomised trials of this agent in prospectively defined high-risk patients are required to clarify its role in the management of severe sepsis.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.