ArticleCurrent infectious disease reports2013
Why activated protein C was not successful in severe sepsis and septic shock: are we still tilting at windmills?
Article in Current infectious disease reports, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 22 citations in OpenAlex.
- The Diagnostic Utility of Host RNA Biosignatures in Adult Patients With Sepsis: A Systematic Review and Meta-Analysis.Critical care explorations · 2025Pooled it
- Sepsis modelling: current approaches and organ-on-chip perspectives.EBioMedicine · 2026Review
- Loss of protein C vs protein S results in discrepant thrombotic phenotypes.Blood advances · 2025Article
- Trauma-associated extracellular histones mediate inflammation via a MYD88-IRAK1-ERK signaling axis and induce lytic cell death in human adipocytes.Cell death & disease · 2024Article
- Targeting the host response in sepsis: current approaches and future evidence.Critical care (London, England) · 2023Review
- Treatment Advances in Sepsis and Septic Shock: Modulating Pro- and Anti-Inflammatory Mechanisms.Journal of clinical medicine · 2023Review
- Inflammasome-mediated GSDMD activation facilitates escape of Candida albicans from macrophages.Nature communications · 2021Article
- Sepsis, Cytokine Storms, and Immunopathology: The Divide between Neonates and Adults.ImmunoHorizons · 2021Article
- Endothelial Injury and Glycocalyx Degradation in Critically Ill Coronavirus Disease 2019 Patients: Implications for Microvascular Platelet Aggregation.Critical care explorations · 2020Article
- Biomaterial-Driven Immunomodulation: Cell Biology-Based Strategies to Mitigate Severe Inflammation and Sepsis.Frontiers in immunology · 2020Review
- Proteases: Pivot Points in Functional Proteomics.Methods in molecular biology (Clifton, N.J.) · 2019Review
- Coagulopathies and inflammatory diseases: '…glimpse of a Snark'.Current opinion in immunology · 2018Review
- Sepsis and septic shock.Nature reviews. Disease primers · 2016Review
- Gene control of tyrosine kinase TIE2 and vascular manifestations of infections.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Mechanisms of phagocytosis and host clearance of Pseudomonas aeruginosa.American journal of physiology. Lung cellular and molecular physiology · 2014Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Drotrecogin alpha activated (DAA), trade name Xigris, is a recombinant human protein C that has been the subject of controversy since 2001, when it became the first biologic agent approved for the treatment of severe sepsis and septic shock. The PROWESS trial showed a 6.1 % absolute reduction in 28-day mortality, although these findings were not replicated in later trials, ultimately leading to the withdrawal of DAA in 2011. Observational trials, however, have consistently shown a mortality benefit with the use of DAA, leading to the following questions: Did DAA truly fail and, if so, why? While these questions may never be definitively answered on the basis of available evidence, several factors may explain the conflicting results. In clinical practice, DAA may have been preferentially given to subjects more likely to survive. Contemporary treatments, including early antibiotic administration and volume resuscitation, may have mitigated the inflammatory processes leading to disordered coagulation and microvascular thrombosis and, thus, reduced or abolished the therapeutic opportunity for DAA. Later randomized clinical trials of DAA focused on the clinical phenotype of refractory shock, largely due to a strong efficacy signal in this subset from PROWESS; however, this clinical phenotype may not be tightly linked, at least after contemporary early resuscitation strategies, to the mechanistic phenotype of dysregulated coagulation that may have been a better target for DAA. Future trials of biologic therapies in severe sepsis and septic shock should use a combination of clinical phenotype and biomarkers to identify responsive populations that may benefit from such therapies.
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.