Table 2

Serious adverse events including bleeding events through clinical trials


Placebo-controlled studies
Open-labela




PROWESS
ADDRESS
ENHANCE
XPRESS





Adverse events
DrotAA (n = 850)
Placebo (n = 840)
DrotAA (n = 1,317)
Placebo (n = 1,293)
DrotAA (n = 2,378)
DrotAA (n = 1,935)

Study drug infusion period*
     Serious events
58 (6.8)
55 (6.5)
75 (5.7)
78 (6.0)
166 (7.0)
128 (6.6)
     Serious bleeds
20 (2.4)
8 (1.0)
31 (2.4)
15 (1.2)
85 (3.6)
46 (2.4)
     CNS bleeds
2 (0.2)
0
4 (0.3)
3 (0.2)
15 (0.6)
6 (0.3)
Days 0 through 28
     Serious events
106 (12.5)
102 (12.1)
182 (13.8)
183 (14.2)
319 (13.4)
256 (13.2)
     Serious bleeds
30 (3.5)
17 (2.0)
51 (3.9)
28 (2.2)
155 (6.5)
88 (4.5)
     CNS bleeds
2 (0.2)
1 (0.1)
6 (0.5)
5 (0.4)
35 (1.5)
17 (0.9)

*In PROWESS and ENHANCE, the study drug infusion period was defined as the actual infusion plus 1 day. In ADDRESS, RESOLVE and XPRESS, the study drug infusion period was defined as study days 0 through 6. Values are expressed as n (%). aENHANCE was an open-label study. XPRESS was a placebo-controlled study of the co-administration of heparin with drotrecogin alfa (activated); the drug under study was heparin; open-label drotrecogin alfa (activated) was administered to all patients. ADDRESS, Efficacy and Safety of Drotrecogin alfa [activated] in Adult Severe Sepsis Patients at Low Risk of Death; CNS, central nervous system; DrotAA, drotrecogin alfa (activated); ENHANCE, Extended Evaluation of Recombinant Human Activated Protein C, drotrecogin alfa (activated); PROWESS, Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis; XPRESS, Xigris and Prophylactic Heparin Evaluation in Severe Sepsis. Modified with permission from Williams MD, Macias W, Rustige J: Safety of drotrecogin alfa (activated): a fair comparison requires consistent definitions. Intensive Care Med 2007, 33:1487–1488. © Springer-Verlag.

Fumagalli and Mignini Critical Care 2007 11(Suppl 5):S6   doi:10.1186/cc6157