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Intensive Care Medicine

, Volume 29, Issue 6, pp 894–903 | Cite as

Drotrecogin alfa (activated) in the treatment of severe sepsis patients with multiple-organ dysfunction: data from the PROWESS trial

  • Jean-François Dhainaut
  • Pierre-François Laterre
  • Jonathan M. Janes
  • Gordon R. Bernard
  • Antonio Artigas
  • Jan Bakker
  • Hanno Riess
  • Bruce R. Basson
  • Julien Charpentier
  • Barbara G. Utterback
  • Jean-Louis Vincent
  • Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) Study Group
Original

Abstract

Objective

Based on the results of the PROWESS trial the European Agency for the Evaluation of Medicinal Products has recently approved drotrecogin alfa (activated) for treatment of adult patients with severe sepsis and multiple-organ failure. We report study's data on efficacy and safety in patients with multiple-organ dysfunction.

Design and setting

Randomized, double-blind, placebo-controlled, multicenter trial in 164 medical centers.

Patients

1271 patients (75.2% of the intention-to-treat population, n=1690) with multiple-organ dysfunction at study entry.

Interventions

Drotrecogin alfa (activated) n=634, 24 µg/kg per hour for 96 h or placebo (n=637).

Results

Observed 28-day mortality was significantly lower with drug treatment than with placebo (26.5%vs. 33.9%), cardiovascular and respiratory organ dysfunction resolved more rapidly over the first 7 days, and serious bleeding events were more frequent (2.4% vs. 1.3%).

Conclusions

Treatment with drotrecogin alfa (activated) significantly reduced 28-day mortality and more quickly resolved cardiovascular and respiratory organ dysfunction. The difference in serious bleeding event rates may be clinically significant; however, the overall benefit-risk profile appears favorable.

Keywords

Drotrecogin alfa (activated) Activated protein C Xigris Recombinant proteins Sepsis Septic shock 

Notes

Acknowledgements

The investigation would not have been possible without the effort of the product development team at Eli Lilly and Company. We are indebted to Samiha Sarwat for providing statistical analysis assistance. This study was sponsored by a grant from Eli Lilly and Company, Indianapolis, Ind., USA. J.-F. D had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

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Copyright information

© Springer-Verlag 2003

Authors and Affiliations

  • Jean-François Dhainaut
    • 1
  • Pierre-François Laterre
    • 2
  • Jonathan M. Janes
    • 3
  • Gordon R. Bernard
    • 4
  • Antonio Artigas
    • 5
  • Jan Bakker
    • 6
  • Hanno Riess
    • 7
  • Bruce R. Basson
    • 8
  • Julien Charpentier
    • 1
  • Barbara G. Utterback
    • 8
  • Jean-Louis Vincent
    • 9
  • Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) Study Group
  1. 1.Department of Intensive Care, Cochin Hospital AP-HP, Cochin Institute, Cochin Port-Royal Medical SchoolParis V UniversityParis cedex 14France
  2. 2.Department of Critical Care and Emergency MedicineCliniques Universitaires St. LucBrusselsBelgium
  3. 3.Lilly Research CentreEli Lilly & Co. Ltd.Erl Wood Manor, SurreyUK
  4. 4.Divisions of Allergy, Pulmonary and Critical Care MedicineVanderbilt University School of MedicineNashvilleUSA
  5. 5.Critical Care Center, Sabadell Hospital, University Institute parc TauliAutonomous University of BarcelonaSabadellSpain
  6. 6.Isala KliniekenZwolleThe Netherlands
  7. 7.Universitätsklinikum Charité,Medizinische Klinik für Haematologie und OnkologieHumbolt UniversitätBerlinGermany
  8. 8.Lilly Research LaboratoriesEli Lilly and CompanyIndianapolisUSA
  9. 9.Department of Intensive Care, Erasme University HospitalFree University of BrusselsBrusselsBelgium

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