PROWESS
Trial question
What is the role of drotrecogin alfa activated therapy in patients with systemic inflammation and organ failure due to acute infection?
Study design
Multi-center
Double blinded
RCT
Population
Characteristics of study participants
43.0% female
57.0% male
N = 1690
1690 patients (726 female, 964 male).
Inclusion criteria: patients with systemic inflammation and organ failure due to acute infection.
Key exclusion criteria: pregnancy or breast feeding, age < 18 years, weight > 135 kg, known hypercoagulable condition, moribund state, HIV infection, history of bone marrow, lung, liver, pancreas, or small-bowel transplantation.
Interventions
N=850 drotrecogin alfa activated (24 mcg/kg of body weight per hour for a total duration of 96 hours).
N=840 placebo (0.9% saline with or without 0.1% human serum albumin for a total of 96 hours).
Primary outcome
Death
24.7%
30.8%
30.8 %
23.1 %
15.4 %
7.7 %
0.0 %
Drotrecogin alfa
activated
Placebo
Significant
decrease ▼
NNT = 16
Significant decrease in death (24.7% vs. 30.8%; RR 0.8, 95% CI 0.69 to 0.94).
Secondary outcomes
Significant decrease in risk of death, among patients with protein C deficiency (25.7% vs. 32.1%; RR 0.8, 95% CI 0.68 to 0.95).
Safety outcomes
No significant difference in at least one serious adverse event.
Significant differences in serious bleeding (3.5% vs. 2.0%, p = 0.06).
Conclusion
In patients with systemic inflammation and organ failure due to acute infection, drotrecogin alfa activated was superior to placebo with respect to death.
Reference
Bernard GR, Vincent JL, Laterre PF et al. Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med. 2001 Mar 8;344(10):699-709.
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