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Activated protein C: do more survive?

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References

  1. Dellinger RP, Carlet J, Masur H, Gerlach H, Calandra T, Cohen J, Gea-Banacloche J, Keh D, Marshall JC, Parker MM, Ramsay G, Zimmerman JL, Vincent JL, Levy MM for the Surviving Sepsis Campaign Management Guidelines Committee (2004) Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock. Crit Care Med 32:858–873

    Article  PubMed  Google Scholar 

  2. Bernard GR, Vincent JL, Laterre PF, LaRosa SP, Dhainaut JF, Lopez-Rodriguez A, Steingrub JS, Garber GE, Helterbrand JD, Ely EW, Fisher CJ (2001) Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med 344:699–709

    Article  PubMed  Google Scholar 

  3. United States Food and Drug Administration Anti-Infective Drugs Advisory Committee (2001) Drotrecogin alfa (activated) [recombinant human activated protein C (rhAPC)] Xigris, bla 125029/0. FDA briefing information.http://www.fda.gov/ohrms/dockets/ac/01/briefing/3797b1.htm (accessed 14 July 2005)

  4. United States Food and Drug Administration (2001) FDA clinical review drotrecogin alfa (activated) [recombinant human activated protein C (rhAPC)] Xigris, bla 125029/0, approved 21 November 2001.http://www.fda.gov/cder/biologics/review/droteli112101r1.htm (accessed 14 July 2005)

  5. Lilly (n.d.) Association of Xigris (drotrecogin alfa activated) with mortality in patients with single organ dysfunction and recent surgery: ADDRESS study (letter).http://www.hc-sc.gc.ca/hpfb-dgpsa/tpd-dpt/xigris_nth_e.html (accessed 14 July 2005)

  6. Angus DC, Laterre PF, Helterbrand J, Ely EW, Ball DE, Garg R, Weissfeld LA, Bernard GR for the PROWESS Investigators (2004) The effect of drotrecogin alfa (activated) on long-term survival after severe sepsis. Crit Care Med 32:2199–2206

    PubMed  Google Scholar 

  7. Lilly (2005) Association of Xigris with intracranial hemorrhage in pediatric patients and discontinuation of study F1K-MC-EVBP (investigation of the efficacy and safety of drotrecogin alfa (activated) in pediatric severe sepsis) based on failure to reach desired clinical endpoints and an unfavourable benefit/risk profile, 6 May 2005.http://www.hc-sc.gc.ca/hpfb-dgpsa/tpd-dpt/xigris_hpc_e.html (accessed 14 July 2005)

  8. Angus DC, Laterre PF, Helterbrand J, Ball DE, Garg R, Bernard GR (2002) The effects of drotrecogin alfa (activated) on long-term survival after severe sepsis (abstract). Chest 122 [Suppl]

  9. Laterre PF, Levy H, Clermont G, Ball DE, Garg R, Nelson DR, Dhainaut JF, Angus DC (2004) Hospital mortality and resource use in subgroups of the Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) trial. Crit Care Med 32:2207–2218

    PubMed  Google Scholar 

  10. Warren H. S, Suffredini A. F, Eichacker P. Q, Munford R (2002) Risks and benefits of activated protein C treatment for severe sepsis. N Engl J Med 347:1027–1030

    Article  PubMed  Google Scholar 

  11. Siegel J. P (2002) Assessing the use of activated protein C in the treatment of severe sepsis. N Engl J Med 347:1030–1034

    Article  PubMed  Google Scholar 

  12. Ely EW, Bernard GR, Vincent J-L (2002) Activated protein C for severe sepsis. N Engl J Med 347:1035–1036

    Article  PubMed  Google Scholar 

  13. Anti-infective Drug Advisory Committee (2001) Anti-infective transcript of Anti-infective Drug Advisory Committee meeting, 16 October 2001.http://www.fda.gov/ohrms/dockets/ac/cder01.htm

  14. Villar J, Perez-Mendez L, Aguirre-Jaime A, Kacmarek RM (2005) Why are physicians so skeptical about positive randomized controlled clinical trials in critical care medicine? Intensive Care Med 31:196–204

    Article  PubMed  Google Scholar 

  15. Bernard GR, Margolis BD, Shanies HM, Ely EW, Wheeler AP, Levy H, Wong K, Wright TJ (2004) Extended evaluation of recombinant human activated protein C United States Trial (ENHANCE US): a single-arm, phase 3B, multicenter study of drotrecogin alfa (activated) in severe sepsis. Chest 125:2206–2216

    Article  PubMed  Google Scholar 

  16. National Institute for Clinical Excellence (2004) Technology appraisal guidance 84: drotrecogin alfa (activated) for severe sepsis.http://www.nice.org.uk.

    Google Scholar 

  17. Committee for Medicinal Products for Human Use (2005) Press release EMEA 21 April 2005: meeting of the Committee for Medicinal Products for Human Use.http://www.emea.eu.int/htms/hotpress/h13844405.htm

    Google Scholar 

  18. Deans KJ, Minneci PC, Banks SM, Natanson C, Eichacker PQ (2004) Substantiating the concerns about recombinant human activated protein C use in sepsis. Crit Care Med 32:2542–2543

    Article  PubMed  Google Scholar 

  19. Eichacker PQ, Natanson C (2005) Authors reply to letter. Crit Care Med 33:1467–1468

    Article  PubMed  Google Scholar 

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Acknowledgements

I thank Dr Peter JD Andrews and Dr Charles Wallis (Consultants in Anaesthesia and Intensive Care, Western General Hospital, Edinburgh, Scotland) for their essential input.

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Correspondence to Alasdair F. Mackenzie.

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Mackenzie, A.F. Activated protein C: do more survive?. Intensive Care Med 31, 1624–1626 (2005). https://doi.org/10.1007/s00134-005-2829-4

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  • DOI: https://doi.org/10.1007/s00134-005-2829-4

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