Pharmacy World and Science

, Volume 28, Issue 5, pp 290–295 | Cite as

Evaluation of drotrecogin alpha use in a Belgian university hospital

  • Isabel SprietEmail author
  • Wouter Meersseman
  • Alexander Wilmer
  • Geert Meyfroidt
  • Minne Casteels
  • Ludo Willems
Research Article



Sepsis remains a major cause of mortality in ICU patients, despite advances in therapy. Drotrecogin alpha (Drot AA), a recombinant human activated protein C with anti-inflammatory and anticoagulant properties, has proven to be successful in patients with at least one organ failure. Our goal was to evaluate the data in patients with sepsis and at least two organ dysfunctions in a large university hospital in Belgium.


The study was conducted at the medical and surgical intensive care units of the 1850-bed university hospital of Leuven, Belgium.


We retrospectively evaluated the use of Drot AA during a 2.5 year period. At baseline patients’ demographics, type of infection, APACHE II (acute physiology and chronic health evaluation), SOFA (sequential organ failure assessment), DIC (diffuse intravascular coagulation) score and number of organ failures were obtained. Overall hospital mortality was defined as primary outcome measure. Special attention was paid to bleeding, the main side effect of Drot AA.

Main outcome measure

Evalution of hospital and ICU mortality in patients treated with Drot AA for severe sepsis.


Drot AA was administered to 23 patients with sepsis and at least 2 organ dysfunctions; all patients started treatment within 24 h of onset of the second organ failure. Mean age was 59 years. Mean number of organ failures was 3. Overall hospital mortality rate was 47.8%. A 28-day mortality of 26% was found, comparable with the 28-day mortality rate of the PROWESS trial. Bleeding, requiring more than 3 units of blood, occurred in 1 patient. Although underlying co-morbidity was more pronounced in survivors, non-survivors had a slightly higher median APACHE II, higher SOFA score and higher DIC score. However, the number of organ failures was identical in both groups.


Overall hospital mortality rate was similar as observed in the Belgian Registry and 28-day mortality was equal to the results of the PROWESS study. Due to the limited number of patients, it is not clear if patients should be selected based on APACHE II, DIC or number of organ failures. However, selection based on number of organ failures is more appropriate due to intrinsic problems of the APACHE II score.


Drotrecogin alpha Drug use evaluation Hospital Intensive Care Mortality Organ failure Severe sepsis Sepsis 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


Conflicts of interest

none declared.


  1. 1.
    Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR. Epidemiology of severe sepsis in the United States: analysis of incidence, outcome and associated costs of care. Crit Care Med 2001;29:1303–10PubMedCrossRefGoogle Scholar
  2. 2.
    Dellinger RP, Carlet JM, Masur H, Gerlach H, Calandra T, Cohen J, et al. Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock. Crit Care Med 2004;32:858–73PubMedCrossRefGoogle Scholar
  3. 3.
    Levi M, ten Cate B. Disseminated intravascular coagulation. N Engl J Med 1999;341:586–92PubMedCrossRefGoogle Scholar
  4. 4.
    Yan SB, Helterbrand JD, Hartman DL, Wright TJ, Bernard GR. Low levels of protein C are associated with poor outcomes in sepsis. Chest 2001;120:915–22PubMedCrossRefGoogle Scholar
  5. 5.
    Bernard GR, Vincent JL, Laterre PF, LaRosa SP, Dhainaut JF, Lopez-Rodriguez A, et al. Efficacy and safety of recombinant human activated protein C for severe sepsis. Recombinant Human Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) Study Group. N Engl J Med 2001;344:699–706PubMedCrossRefGoogle Scholar
  6. 6.
    Vincent J, Laterre P, Janes J, Nelson D, Haentjens T, Sartral M, et al. Analysis of Drotrecogin alfa (activated) use in Belgium: Comparison to PROGRESS Registry Data. Abstract 227 presented at the ESICM, European Society of Intensive Care Medicine, Amsterdam, September, 2005Google Scholar
  7. 7.
    Package insert. Xigris (drotrecogin alpha). Eli Lilly, Houten, The Netherlands, January 2005.Google Scholar
  8. 8.
    Moniteur Belge - Belgisch Staatsblad nr. 325, Ministerial Decree 21–10–2005: Terugbetaling van Xigris.Google Scholar
  9. 9.
    Knaus WA, Draper EA, Wagner DP, Zimmerman JE. APACHE II: a severity of disease classification system. Crit Care Med 1985;13:818–29PubMedCrossRefGoogle Scholar
  10. 10.
    Vincent J, Moreno R, Takala J, et al. The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. Intensive Care Med 1996;22:707–10PubMedGoogle Scholar
  11. 11.
    Dhainaut JF, Yan SB, Joyce DE, Pettilä V, Basson B, Brandt JT, et al. Treatment effects of drotrecogin alfa (activated) in patients with severe sepsis with or without overt disseminated intravascular coagulation. J Thromb Haemost 2004;2:1924–33PubMedCrossRefGoogle Scholar
  12. 12.
    Warren HS, Suffredini AF, Eichacker PQ, Munford RS. Risks and benefits of activated protein C treatment for severe sepsis. N Engl J Med 2002;347:1027–30PubMedCrossRefGoogle Scholar
  13. 13.
    Siegel JP. Assessing the use of activated protein C in the treatment of severe sepsis. N Engl J Med 2002;347:1030–34PubMedCrossRefGoogle Scholar
  14. 14.
    Parillo JE. Severe sepsis and therapy with activated protein C. N Engl J Med 2005;353:1398–400CrossRefGoogle Scholar
  15. 15.
    Eichacker PQ, Danner RL, Suffredini AF, Cui X, Natanson C. Reassessing recombinant human activated protein C for sepsis: Time for a new randomized controlled trial. Crit Care Med 2005;10:2426–8CrossRefGoogle Scholar
  16. 16.
    Mackenzie AF. Activated protein C: do more survive? Intens Care Med 2005;31:1624–6CrossRefGoogle Scholar
  17. 17.
    Abraham E, Laterre PF, Garg R, Levy H, Talwar D, Trzaskoma BL, et al. Drotrecogin alfa (activated) for adults with severe sepsis and a low risk of death. Administration of drotrecogin alfa (activated) in early stage severe sepsis (ADDRESS) Study Group. N Engl J Med 2005;353:1332–41PubMedCrossRefGoogle Scholar
  18. 18.
    FDA warning surgical patients. Available from Accessed March 15, 2006.
  19. 19.
    Vincent JL, Bernard GR, Beale R, Doig C, Putensen C, Dhainaut JF, et al. Drotrecogin alpha (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;33:2266–77PubMedCrossRefGoogle Scholar
  20. 20.
    FDA warning pediatrics. Available from http://www.fda. gov/medwatch/SAFETY/2005/Xigris_dearhcp_4-21-05.pdf. Accessed March 15, 2006.
  21. 21.
    Pelloquin A, Zimner S, Camps E. Use of Drotrecogin Alpha (Xigris) in Pitie-Salpetriere hospital. Abstract DI-73 presented at the 5th Spring Conference on Clinical Pharmacy, European Society of Clinical Pharmacy, Stockholm, May 25–28, 2005.Google Scholar
  22. 22.
    Schlecht D, Dallay S, Bauer S, Ferrandiere M, Grassin J, Antier D. One year analysis of prescriptions of drotrecogin alfa (activated) in medical and surgical intensive care units. Abstract DI-218 presented at the 34th European Symposium on Clinical Pharmacy, European Society of Clinical Pharmacy, Amsterdam, October 26–29, 2005Google Scholar
  23. 23.
    Vincent JL, O’Brien J, Wheeler A, Wittebole X, Garg R, Trzaskoma BL et al. Use of an integrated clinical trial database to evaluate the effect of timing of drotrecogin alfa (activated) treatement in severe sepsis. Crit Care 2006;10(3):R74PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2006

Authors and Affiliations

  • Isabel Spriet
    • 1
    Email author
  • Wouter Meersseman
    • 2
  • Alexander Wilmer
    • 2
  • Geert Meyfroidt
    • 3
  • Minne Casteels
    • 4
  • Ludo Willems
    • 1
  1. 1.Pharmacy DepartmentUniversity Hospital of LeuvenLeuvenBelgium
  2. 2.Medical Intensive Care UnitUniversity Hospital of LeuvenLeuvenBelgium
  3. 3.Surgical Intensive Care UnitUniversity Hospital of LeuvenLeuvenBelgium
  4. 4.Pharmacology DepartmentUniversity Hospital of LeuvenLeuvenBelgium

Personalised recommendations