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.