Trial reportIntensive care medicine2009
Extended drotrecogin alfa (activated) treatment in patients with prolonged septic shock.
Trial report in Intensive care medicine, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 18 papers, 4 of them syntheses 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
18 citing papers in PubMed, 4 syntheses or guidelines pooled it, 33 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
- Control groups in recent septic shock trials: a systematic review.Intensive care medicine · 2016Pooled 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
- A Randomized Controlled Trial of Behavioral Nudges to Improve Enrollment in Critical Care Trials.Annals of the American Thoracic Society · 2020Trial
- Endothelial dysfunction and immunothrombosis in sepsis.Frontiers in immunology · 2023Review
- Vasopressor-Sparing Strategies in Patients with Shock: A Scoping-Review and an Evidence-Based Strategy Proposition.Journal of clinical medicine · 2021Article
- Protein C Pathway in Paediatric and Neonatal Sepsis.Frontiers in pediatrics · 2021Review
- Vasopressor requirement during targeted temperature management for out-of-hospital cardiac arrest caused by acute myocardial infarction without cardiogenic shock.Clinical and experimental emergency medicine · 2016Article
- The efficacy of activated protein C for the treatment of sepsis: incorporating observational evidence with a Bayesian approach.BMJ open · 2015Article
- Why activated protein C was not successful in severe sepsis and septic shock: are we still tilting at windmills?Current infectious disease reports · 2013Article
- Persistent hypocoagulability in patients with septic shock predicts greater hospital mortality: impact of impaired thrombin generation.Intensive care medicine · 2012Article
- An update on activated protein C (xigris) in the management of sepsis.P & T : a peer-reviewed journal for formulary management · 2010Article
- Case report: perioperative use of protein c concentrate for protein C deficiency in THA.Clinical orthopaedics and related research · 2010Article
- Managing septic shock.F1000 medicine reports · 2010Article
- Activated protein C action in inflammation.British journal of haematology · 2010Review
- Year in review in Intensive Care Medicine 2009: I. Pneumonia and infections, sepsis, outcome, acute renal failure and acid base, nutrition and glycaemic control.Intensive care medicine · 2010Review
- Growing insights into the potential benefits and risks of activated protein C administration in sepsis: a review of preclinical and clinical studies.Biologics : targets & therapy · 2009Article
Corrections and comments
- Erratum issued
Authors and funding
12 authors at 9 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveTo determine the efficacy and safety of extended drotrecogin alfa (activated) (DAA) therapy.
designMulticentre, randomised, double-blind, placebo-controlled study.
settingSixty-four intensive care units in nine countries. PATIENTS: Adults with severe sepsis and vasopressor-dependent hypotension after a 96-h infusion of standard DAA.
interventionsA total of 193 patients received an intravenous infusion of extended DAA 24 microg/kg/h or sodium chloride placebo for a maximum of 72 h. MEASUREMENTS AND
resultsAt extended therapy initiation (baseline), DAA-group patients had lower protein C levels (P = 0.23) and higher vasopressor requirements, particularly for the primary vasopressor used, norepinephrine (P = 0.03), compared with placebo-group patients. DAA treatment did not result in a difference in the primary outcome of time to resolution of vasopressor-dependent hypotension versus placebo (P = 0.419). However, few patients reached resolution (DAA 34%, placebo 40%) as most continued to require vasopressor support after 72 additional hours of treatment. Treatment did not reduce 28-day all-cause mortality and in-hospital mortality or improve organ function compared with placebo, although there was a lower percentage change in D-dimers (P < 0.001) and increases in protein C levels were numerically greater on extended infusion. There was no difference in serious adverse events including bleeding events.
conclusionsExtended DAA treatment did not result in more rapid resolution of vasopressor-dependent hypotension, despite demonstrating anticipated biological effects on D-dimer and protein C levels. A reduced planned sample size combined with baseline imbalances in protein C levels and vasopressor requirements may have limited the ability to demonstrate a clinical benefit.
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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.