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. 2010 Sep;35(9):504-508, 529.

Table 1.

Summary of Significant Studies of Activated Protein C (Xigris)

Trial No. of Patients Year Objective Design Main Outcomes Author
Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) 1,690 2001 All-cause mortality at 28 days R, DB, PC, MC Mortality: placebo, 30.8% vs. treatment, 24.7% (P = 0.005) Bernard2
Administration of Drotrecogin Alfa (Activated) in Early-Stage Severe Sepsis (ADDRESS) 2,640 2005 All-cause mortality at 28 days in patients with severe sepsis and low risk of death R, DB, PC, MC Mortality: placebo, 17% vs. treatment, 18.5% (P = 0.34) Abraham5
Researching Severe Sepsis and Organ Dysfunction in Children: A Global Perspective Study (RESOLVE) 477 2007 CTCOFR: mortality and safety at 28 days R, DB, PC, MC CTCOFR: no difference between groups (P = 0.72)

  • Mortality: placebo, 17.5% vs. treatment, 17.2% (P = 0.93)

  • CNS bleeding: placebo, 2.1% vs. treatment, 4.6% (P = 0.13)

 Nadel12
Human recombinant activated protein C for severe sepsis (review) 4,911 2008 All-cause mortality at 28 days M Relative risk = 0.92 (95% CI, 0.72–1.18; P = 0.42) Marti-Carvajal17
Extended Evaluation of Human Recombinant Activated Protein C (ENHANCE) 2,375 2005 All-cause mortality and safety at 28 days SA, OL

  • Mortality: 25.3%

  • Serious bleeding: 6.5% at 28 days

 Vincent19
Use of drotrecogin alfa (activated) in Italian intensive-care units 668 2007 Clinical outcomes Survey (with NPC) Mortality: increased in surgical patients (within 7 days); odds ratio = 2.79 Bertolini21
Evaluating use of drotrecogin alfa (activated) in adult patients with severe sepsis: a Canadian multicenter observational study 261 2007 Usage patterns and clinical outcomes Survey

  • Mortality: 45%

  • Serious bleeding: 10%

 Kanji22
Adverse outcomes in patients with severe sepsis and baseline bleeding precautions 73 2009 Outcomes in patients with baseline bleeding precautions (outlined in PROWESS) RT

  • Serious bleeding: 35% vs. 3.8% for patients without bleeding risks (P < 0.0001)

  • Mortality: 65% vs. 24.5% (P = 0.0015)

 Gentry23
Xigris and Prophylactic Heparin Evaluation in Severe Sepsis (XPRESS) 1,994 2009 All-cause mortality at 28 days R, DB, PC, MC

  • Mortality: heparin, 28.3% vs. placebo, 31.9% (P = 0.08)

  • Mortality of subgroup:* 26.9% vs. placebo, 35.6% (P = 0.005)

 Levi26
Extended drotrecogin alfa (activated) infusions in prolonged septic shock 193 2009 Primary: resolution of shock within 72 hours after initial 96 hours of therapy
Secondary: all-cause mortality at 28 days		 R, DB, PC, MC

  • Shock resolution: 34% vs. placebo, 40% (P = 0.419)

  • Mortality: treatment, 39.8% vs. placebo, 32.3% (P = 0.283)

 Dhainaut28

CI = confidence interval; CNS = central nervous system; CTCOFR = composite time to complete primary organ failure resolution; DB = double-blind; M = meta-analysis; MC = multicenter; NPC = non-parallel control group; OL = open-label; PC = placebo-controlled; R = randomized; SA = single-arm; RT = retrospective.

*

This subgroup of patients was receiving heparin at the baseline evaluation.