A safety evaluation of drotrecogin alfa (activated) in hematopoietic stem cell transplant patients with severe sepsis: Lessons in clinical research Journal Article


Authors: Pastores, S. M.; Shaw, A.; Williams, M. D.; Mongan, E.; Alicea, M.; Halpern, N. A.
Article Title: A safety evaluation of drotrecogin alfa (activated) in hematopoietic stem cell transplant patients with severe sepsis: Lessons in clinical research
Abstract: We conducted an open-label, multicenter, single-arm clinical trial to investigate the safety and efficacy of drotrecogin alfa (activated) (Drot AA) in hematopoietic stem cell transplant (HSCT) patients with severe sepsis. Drot AA was administered as a continuous i.v. infusion of 24μg/kg/h for 96h. The target enrollment was 250 patients in 15-20 transplant centers over a 2-year period (March 2003-March 2005). However, after only 10 months, in December 2003, the trial was stopped due to a low enrollment of seven patients at three of the 15 sites that were open for accrual. Six of the seven patients completed the drug infusion. Two patients experienced serious bleeding events. The first patient developed a nonfatal diffuse alveolar hemorrhage 2 days after study-drug completion. The second patient had severe coagulopathy and developed a fatal intracranial hemorrhage on the third day of drug infusion. Three of the seven patients were alive 100 days after the HSCT. The slow enrollment rate was attributed to changes in transplant preparatory regimens, enhancements in antimicrobial prophylactic protocols and the use of antimicrobial-coated catheters. The small number of patients in this report precludes a definitive assessment of the safety and efficacy of Drot AA in HSCT patients. © 2005 Nature Publishing Group. All rights reserved.
Keywords: adult; clinical article; middle aged; leukemia; clinical trial; drug efficacy; drug safety; stem cell transplantation; hematopoietic stem cell transplantation; continuous infusion; cause of death; drug fatality; antiinfective agent; multicenter study; recombinant proteins; lymphoma; thrombocyte count; drug infusion; catheterization; sepsis; allogeneic hematopoietic stem cell transplantation; safety; blood clotting disorder; catheter infection; brain hemorrhage; autologous hematopoietic stem cell transplantation; thrombocyte transfusion; multiple organ failure; lung hemorrhage; anti-infective agents; septic shock; aminocaproic acid; protein c; critical care drotrecogin alfa (activated); severe sepsis; drotrecogin
Journal Title: Bone Marrow Transplantation
Volume: 36
Issue: 8
ISSN: 0268-3369
Publisher: Nature Publishing Group  
Date Published: 2005-10-01
Start Page: 721
End Page: 724
Language: English
DOI: 10.1038/sj.bmt.1705124
PUBMED: 16086043
PROVIDER: scopus
DOI/URL:
Notes: --- - "Cited By (since 1996): 7" - "Export Date: 24 October 2012" - "CODEN: BMTRE" - "Source: Scopus"
Altmetric Score
MSK Authors
  1. Neil A Halpern
    115 Halpern
  2. Stephen Pastores
    146 Pastores
  3. Margarita Alicea
    10 Alicea