Introduction:
Surgical patients with severe sepsis commonly receive VTE prophylaxis with heparin. The XPRESS trial evaluated the outcome and safety profile of concomitant administration of drotrecogin alfa (activated) (DrotAA) and prophylactic-dose heparin in high-risk severe sepsis.
Hypothesis: Methods:
XPRESS was a randomized, double-blind, equivalency study of prophylactic-dose heparin versus placebo in patients treated with DrotAA (24 mcg/kg/hr) for 96 hrs. Patients were randomized to heparin or placebo (1:1:2 enoxaparin 40mg SC QD, or unfractionated heparin 5000mg SC Q12h, or placebo). Recent surgery was noted if performed within 7 days preceding enrollment. The primary outcome was 28-day mortality. Statistical methods were ANOVA on the ranks and chi-square.
Results:
Compared to patients without recent surgery (n=1266), patients with recent surgery (n=661) were slightly older (60.0 vs. 58.5 yrs, p=0.06), had greater disease severity as measured by baseline vasopressor support (90.2% vs. 83.5%, p<0.0001), ventilator support (94.6% vs. 84.6%, p<0.0001) and multiple organ dysfunction (92.7% vs. 89.4%, p=0.02), while APACHE II scores were lower (22.9 vs. 24.4, p<0.0001). Within the surgical subgroup, 28-day mortality rates were similar in patients receiving DrotAA with either heparin, 25.5% (84/329) or placebo, 25.7% (85/331), p=0.97. Differences in serious bleeding events with the addition of heparin did not reach statistical significance (days 0-6: 3.0% vs. 2.4%, p=0.63; days 0-28: 5.2% vs. 4.8%, p=0.85). Nonserious bleeding events were increased in patients receiving heparin (days 0-6: 10.3% vs. 6.3%, p=0.07; days 0-28: 10.6% vs. 6.3%, p=0.05).
Conclusions:
In the XPRESS surgical subgroup, concomitant prophylactic-dose heparin did not diminish the efficacy of DrotAA or significantly increase the rate of serious bleeding, while nonserious bleeding was increased.