PROWESS-SHOCK
Trial question
What is the role of drotrecogin alfa (activated) in patients with septic shock?
Study design
Multi-center
Double blinded
RCT
Population
Characteristics of study participants
44.0% female
56.0% male
N = 1696
1696 patients (739 female, 957 male).
Inclusion criteria: patients with infection, systemic inflammation, and shock who were receiving fluids and vasopressors above a threshold dose for 4 hours.
Key exclusion criteria: age < 18 years, no evidence of infection, coexisting illnesses with a high risk of death (e.g., metastatic cancer), major bleeding, pregnant or lactating, INR > 5.0, or sepsis induced organ dysfunction > 36 hours.
Interventions
N=851 drotrecogin alfa activated (24 mcg/kg of body weight per hour for 96 hours).
N=845 placebo (matching placebo for 96 hours).
Primary outcome
Death at 28 days
26.4%
24.2%
26.4 %
19.8 %
13.2 %
6.6 %
0.0 %
Drotrecogin alfa
activated
Placebo
No significant
difference ↔
No significant difference in death at 28 days (26.4% vs. 24.2%; RR 1.09, 95% CI 0.92 to 1.28).
Secondary outcomes
No significant difference in death at 90 days (34.1% vs. 32.7%; RR 1.04, 95% CI 0.9 to 1.19).
No significant difference in death at 28 days, among patients with severe protein C deficiency (28.7% vs. 30.8%; RR 0.93, 95% CI 0.74 to 1.17).
Safety outcomes
No significant differences in serious bleeding (1.2% vs. 1.0%, p=0.81) and serious adverse events (14.3% vs. 11.5%, p=0.10).
Conclusion
In patients with infection, systemic inflammation, and shock who were receiving fluids and vasopressors above a threshold dose for 4 hours, drotrecogin alfa activated was not superior to placebo with respect to death at 28 days.
Reference
Ranieri VM, Thompson BT, Barie PS et al. Drotrecogin alfa (activated) in adults with septic shock. N Engl J Med. 2012 May 31;366(22):2055-64.
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