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Drotrecogin alfa activated as a treatment for severe sepsis in pediatric cancer

Bone Marrow Transplantation volume 38, pages 575–576 (2006)Cite this article

Active protein C is an endogenous modulator of both coagulation and inflammation. Imbalanced activation of protein C may occur as a consequence of inflammatory cytokines. A decreased level of activated protein C in patients with sepsis has been implicated as having a key role in determining multi-organ impairment.1

The availability of a recombinant form of human-activated protein C led to a multi-center, randomized, double-blind, placebo-controlled trial in adults with severe sepsis (PROWESS trial). Publication of these results in 2001 raised the hopes of all physicians who had lost a patient to severe sepsis.2 The trial showed that the use of Drotrecogin alfa activated (Drot AA) decreased mortality (19.4% reduction of the relative risk of death), but increased the risk of serious bleeding (3.5% in the treated group vs 2% in the placebo group, P=0.06). Pastores et al.3 report on a phase-IV, open-label, clinical trial designed for hematopoietic stem cell transplant (HSCT) patients with severe sepsis. The primary end point was to investigate the safety of Drot AA in HSCT patients with severe sepsis assessed as the rate of intracranial hemorrhage and other severe bleeding. However, the authors were unable to complete the trial, which was stopped prematurely due to slow accrual (only seven patients enrolled in 10 months), when it became clear that achieving the study end points was not feasible.

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Authors and Affiliations

  1. Department of Pediatric Hematology/Oncology, University of Catania, Catania, Italy

    G Russo & M La Spina

  2. Department of Anesthesia, University of Catania, Catania, Italy

    N Disma & M Astuto

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  1. G Russo
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  2. M La Spina
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  3. N Disma
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  4. M Astuto
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Russo, G., La Spina, M., Disma, N. et al. Drotrecogin alfa activated as a treatment for severe sepsis in pediatric cancer. Bone Marrow Transplant 38, 575–576 (2006). https://doi.org/10.1038/sj.bmt.1705483

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