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- Title
2012 - Drotrecogin alfa (activated) did not reduce mortality at 28 or 90 days in patients with septic shock.
- Authors
Brun-Buisson, Christian
- Abstract
Question: Does drotrecogin alfa (activated) (DrotAA) reduce mortality in patients with septic shock? Methods Design: Randomized placebo-controlled trial (Prospective Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis and Septic Shock [PROWESS-SHOCK] study) Allocation: Concealed. Blinding: Blinded* (patients, clinicians, investigators, and sponsors). Follow-up period: 90 days. Setting: 208 sites in Europe, North and South America, Australia, New Zealand, and India. Patients: 1697 patients <img alt=">=" src="ge9.gif"/> 18 years of age (mean age 63 y, 56% men) who had sepsis (infection and <img alt=">=" src="ge9.gif"/> 2 signs of systemic inflammation), shock (norepinephrine, <img alt=">=" src="ge9.gif"/> 5 µg/min, or equivalent dose of another vasopressor for <img alt=">=" src="ge9.gif"/> 4 h, and crystalloid, <img alt=">=" src="ge9.gif"/> 30 mL/kg body weight, or equivalent colloid volume within 8 h of vasopressor initiation), and evidence of hypoperfusion; were refractory to vasopressor weaning; and began the study drug <img alt="<=" src="le9.gif"/> 24 hours after the first dose of a vasopressor. Patients with coexisting illness at high risk for death were excluded. Intervention: IV DrotAA (Xigris, Eli Lilly), 24 µg/kg body weight/h for 96 hours (n = 852), or placebo (0.9% saline) (n = 845). If study infusions were interrupted for procedures, they continued to day 6 to complete the 96-hour infusion. Outcomes: Primary outcome was 28-day mortality. Secondary outcomes included 90-day mortality, serious adverse events, and bleeding events. 1500 patients were needed to detect a 7% absolute reduction from 35% in 28-day mortality (80% power, α = 0.05); sample size was increased to 1696 because mortality rate after recruitment of 750 patients was 28%. Patient follow-up: 98% at 90 days (intention-to-treat analysis). Main results: DrotAA did not reduce mortality at 28 or 90 days (Table). Risk for nonserious bleeding events during treatment was higher with DrotAA (Table). Conclusion: Drotrecogin alfa (activated) did not reduce mortality at 28 or 90 days in patients with septic shock.
- Publication
ACP Journal Club, 2012, Vol 157, Issue 4, p1
- ISSN
1056-8751
- Publication type
Academic Journal
- DOI
10.7326/0003-4819-157-4-201208210-02011