Trial reportCritical care (London, England)2010
Randomized trial evaluating serial protein C levels in severe sepsis patients treated with variable doses of drotrecogin alfa (activated).
Trial report in Critical care (London, England), 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00386425 (A Phase 2 Study to Evaluate Dose and Duration of Treatment of Drotrecogin Alfa), which is not on this map. Cited by 13 papers, 5 of them syntheses that pooled it.
What it found
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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.
A Phase 2 Study to Evaluate Dose and Duration of Treatment of Drotrecogin Alfa (Activated) Using Serial Measurements of Protein C in Patients With Severe Sepsis and Multiple Organ Dysfunction
Who cites it
13 citing papers in PubMed, 5 syntheses or guidelines pooled it, 16 citations in OpenAlex.
- Trends in sepsis mortality over time in randomised sepsis trials: a systematic literature review and meta-analysis of mortality in the control arm, 2002-2016.Critical care (London, England) · 2019Pooled it
- An updated meta-analysis to understand the variable efficacy of drotrecogin alfa (activated) in severe sepsis and septic shock.Minerva anestesiologica · 2013Pooled it
- Human recombinant protein C for severe sepsis and septic shock in adult and paediatric patients.The Cochrane database of systematic reviews · 2012Pooled it
- Nebulized anticoagulants for acute lung injury - a systematic review of preclinical and clinical investigations.Critical care (London, England) · 2012Pooled it
- Recombinant human activated protein C for severe sepsis in neonates.The Cochrane database of systematic reviews · 2012Pooled it
- Re-Evaluating Biologic Pharmacotherapies that Target the Host Response during Sepsis.International journal of molecular sciences · 2019Review
- Activated protein C: A regulator of human skin epidermal keratinocyte function.World journal of biological chemistry · 2014Review
- Plasma endothelial protein C receptor influences innate immune response in ovarian cancer by decreasing the population of natural killer and TH17 helper cells.International journal of oncology · 2013Article
- Biomarkers in sepsis.Current opinion in pulmonary medicine · 2013Review
- Prognostic utility and characterization of cell-free DNA in patients with severe sepsis.Critical care (London, England) · 2012Observational
- [Update: studies in intensive care medicine. Results of the last 12 months].Der Anaesthesist · 2011Review
- Treatment with recombinant human activated protein C: one size does not fit all.Critical care (London, England) · 2011Article
- Endothelial Dysfunction Is Associated with Mortality and Severity of Coagulopathy in Patients with Sepsis and Disseminated Intravascular Coagulation.Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/HemostasisArticle
Corrections and comments
- Commented on by
Authors and funding
14 authors at 9 institutions in 7 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionSerial alterations in protein C levels appear to correlate with disease severity in patients with severe sepsis, and it may be possible to tailor severe sepsis therapy with the use of this biomarker. The purpose of this study was to evaluate the dose and duration of drotrecogin alfa (activated) treatment using serial measurements of protein C compared to standard therapy in patients with severe sepsis.
methodsThis was a phase 2 multicenter, randomized, double-blind, controlled study. Adult patients with two or more sepsis-induced organ dysfunctions were enrolled. Protein C deficient patients were randomized to standard therapy (24 μg/kg/hr infusion for 96 hours) or alternative therapy (higher dose and/or variable duration; 24/30/36 μg/kg/hr for 48 to 168 hours). The primary outcome was a change in protein C level in the alternative therapy group, between study Day 1 and Day 7, compared to standard therapy.
resultsOf 557 patients enrolled, 433 patients received randomized therapy; 206 alternative, and 227 standard. Baseline characteristics of the groups were largely similar. The difference in absolute change in protein C from Day 1 to Day 7 between the two therapy groups was 7% (P = 0.011). Higher doses and longer infusions were associated with a more pronounced increase in protein C level, with no serious bleeding events. The same doses and longer infusions were associated with a larger increase in protein C level; higher rates of serious bleeding when groups received the same treatment; but no clear increased risk of bleeding during the longer infusion. This group also experienced a higher mortality rate; however, there was no clear link to infusion duration.
conclusionsThe study met its primary objective of increased protein C levels in patients receiving alternative therapy demonstrating that variable doses and/or duration of drotrecogin alfa (activated) can improve protein C levels, and also provides valuable information for incorporation into potential future studies.
trial registrationClinicalTrials.gov identifier: NCT00386425.
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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.