Hostname: page-component-78c5997874-g7gxr Total loading time: 0 Render date: 2024-11-10T10:47:04.520Z Has data issue: false hasContentIssue false
  • English
  • Français

Drotrecogin alfa (activated): diffusion from clinical trials to clinical practice

Published online by Cambridge University Press:  01 March 2008

S. Ridley ,
A. Lwin ,
D. Wyncoll ,
S. Lippett ,
D. Watson ,
K. Gunning  and
D. Higgins
S. Ridley*
Affiliation:
Glan Clwyd Hospital, Department of Anaesthesia and Intensive Care, Rhyl, Denbighshire, UK
A. Lwin
Affiliation:
Norfolk & Norwich University Hospital, Department of Acute and General Medicine, Norwich, UK
D. Wyncoll
Affiliation:
Guy’s & St Thomas’ NHS Foundation Trust, Department of Critical Care, London, UK
S. Lippett
Affiliation:
Guy’s & St Thomas’ NHS Foundation Trust, Department of Critical Care, London, UK
D. Watson
Affiliation:
University Hospitals Coventry and Warwickshire NHS Trust, Department of Anaesthesia and Intensive Care, London, UK
K. Gunning
Affiliation:
Addenbrookes Hospital, Department of Anaesthesia and Intensive Care, Cambridge, UK
D. Higgins
Affiliation:
Southend NHS Trust, Department of Anaesthesia and Intensive Care, London, UK
*
Correspondence to: Saxon Ridley, Department of Anaesthesia and Intensive Care, Glan Clwyd Hospital, Rhyl, Denbighshire LL18 5UJ, UK. E-mail: saxon@ridley.waitrose.com; Tel: +44 1745 583910; Fax: +44 1745 583143
Get access

Summary

Backgound and objective

Although the PROWESS trial demonstrated a mortality benefit, subsequent studies in different patient populations have not reproduced the effect. As a result, concerns have been expressed about the clinical effectiveness of drotrecogin alfa (activated). Therefore the aim of this audit was to review the clinical impact of drotrecogin alfa (activated) when used outside clinical trials.

Methods

A retrospective review of ICU charts and medical records of patients who had received drotrecogin alfa (activated) in the five largest users of drotrecogin alfa (activated) in England. Patients characteristics details at ICU admission and vital status at hospital discharge were recorded. The severity of illness was assessed by the APACHE II score (using first 24 h admission data) and the number of organ dysfunctions. Adverse incidents were recorded and any sequence effect explored.

Results

In all, 351 patients received drotrecogin alfa (activated) between December 2002 and November 2005. Of those, 201 (57.2%) were male, and 177 (50.4%) were admitted after recent surgery. The patients’ average age was 61.8 yr. The mean admission APACHE II score was 23.3 and the average number of dysfunctional organs on admission was 3.3. The hospital mortality was 46.7% (164 deaths). The expected number of deaths calculated by using the APACHE II risk of death was 173 (49.3%) and by number of sepsis induced organ failures 210 (59.7%). Overall, there were 33 (9.4%) adverse incidents.

Conclusions

Expected mortality derived from both the APACHE II score and organ dysfunctions suggests that drotrecogin alfa (activated) does reduce mortality. Serious adverse incidents occurred in 5.1% patients; however, the direct contributing effect of drotrecogin alfa (activated) cannot be established from this type of audit.

Keywords

DROTRECOGIN ALPHAMULIPTLE ORGAN FAILURESEPSISCRITICAL CAREMORTALITY AND MORBIDITY
Type
Original Article
Information
European Journal of Anaesthesiology , Volume 25 , Issue 3 , March 2008 , pp. 211 - 216
Copyright
Copyright © European Society of Anaesthesiology 2008

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1.Bernard, GR, Vincent, JL, Laterre, PF et al. . Recombinant human protein C Worldwide Evaluation in Severe Sepsis (PROWESS) study group Efficacy and safety of recombinant activated protein C for severe sepsis. N Engl J Med 2001; 344: 699–709.CrossRefGoogle Scholar
2. National Institute for Clinical Excellence. Drotrecogin alfa (activated) for severe sepsis. Technology Appraisal 84; September 2004. http://www.nice.org.uk/pdf/TA084guidance.pdf (accessed 22/04/2006).Google Scholar
3.Vincent, JL, Bernard, GR, Beale, R et al. . Drotrecogin alfa (activated) treatment in severe sepsis from the global open-label trial ENHANCE: further evidence for survival and safety and implications for early treatment. Crit Care Med 2005; 33: 2266–2277.CrossRefGoogle ScholarPubMed
4.Abraham, E, Laterre, PF, Garg, R et al. . Administration of Drotrecogin Alfa (Activated) in Early Stage Severe Sepsis (ADDRESS) Study Group. (2005) Drotrecogin alfa (activated) for adults with severe sepsis and a low risk of death. N Engl J Med 2005; 353: 1332–1341.CrossRefGoogle Scholar
5.Mackenzie, AF. Conflict of opinion – is PROWESS real progress. Intensive Care Med 2006; 31: 1624–1626.CrossRefGoogle Scholar
6.Dellinger, RP. Recombinant activated protein C: the key is clinical assessment of risk of death, not subset analysis. Crit Care 2006; 10: 114–115.CrossRefGoogle Scholar
7.Macias, WL, Vallet, B, Bernard, GR et al. . Sources of variability on the estimate of treatment effect in the PROWESS trial: implications for the design and conduct of future studies in severe sepsis. Crit Care Med 2004; 32: 2385–2391.CrossRefGoogle ScholarPubMed
8.Knaus, WA, Draper, EA, Wagner, DP, Zimmerman, JE. APACHE II: a severity of disease classification system. Crit Care Med 1985; 13: 818–829.CrossRefGoogle ScholarPubMed
9.Padkin, A, Goldfrad, C, Brady, AR, Young, D, Black, N, Rowan, K. Epidemiology of severe sepsis occurring in the first 24 hrs in intensive care units in England, Wales, and Northern Ireland. Crit Care Med 2003; 31: 2332–2338.CrossRefGoogle ScholarPubMed
10.Vincent, JL, Moreno, R, Takala, J et al. . The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine. Intensive Care Med 1996; 22: 707–710.CrossRefGoogle Scholar
11.Davies, A, Ridley, S, Hutton, J, Chinn, C, Barber, B, Angus, DC. Cost effectiveness of drotrecogin alfa (activated) for the treatment of severe sepsis in the United Kingdom. Anaesthesia 2005; 60: 155–162.CrossRefGoogle ScholarPubMed
12.Kubler, A, Mayzner-Zawadzka, E, Durek, G et al. . Results of severe sepsis treatment program using recombinant human activated protein C in Poland. Med Sci Morit 2006; 12: CR107–CR112.Google ScholarPubMed
13.Vincent, J, Laterre, P, Janes, J et al. . Analysis of drotrecogin alfa (activated) use in Belgium: comparison to Progress Registry Data. Intensive Care Med 2005; 31 (Suppl 1): S62.Google Scholar