Background: Recent trials (ARISE, ProCESS) showed EGDT provided no mortality benefit over usual care. Questions remain about the effectiveness of intensive monitoring protocols, as well as the evolution of what constitutes usual care. The ProMISe trial seeks to test the hypothesis that EGDT impacts mortality in a cost-effective way.
Study design: Pragmatic, open, multicenter, parallel group RCT.
Setting: English National Health Service hospitals that did not routinely use EGDT that included continuous ScvO2 monitoring.
Synopsis: The authors enrolled 1,260 adult patients with early severe sepsis or septic shock; they randomized patients to either usual care or EGDT for six hours. Data was collected prospectively on the EGDT group and retrospectively on the usual care group.
By intention-to-treat analysis, all-cause mortality at 90 days was not significantly different (unadjusted RR 1.01, 95% CI, 0.85-1.20; adjusted OR 0.95, 95% CI, 0.74-1.24, P=0.73). EGDT patients received more intensive therapy, their quality of life scores were similar, and their average costs were higher, though not statistically significant. The probability that EGDT was cost effective was calculated to be below 20%.
Usual care patients had lower-than-expected mortality (29% vs. 40%), limiting the treatment effect of EGDT and limiting extrapolation to groups with higher mortality. Comparison to older studies is limited by the evolution in usual care for sepsis, with earlier recognition and antibiotic administration and greater use of vasoactive drugs. This study adds significant information about quality of life and cost to the discussion about EGDT.
Bottom line: The ProMISe study completes a powerful trio of papers suggesting that EGDT might be an expensive option that offers no clinical benefit over usual care.
Citation: Mouncey PR, Osborn TM, Power GS, et al. Trial of early, goal-directed resuscitation for septic shock. N Engl J Med. 2015;372:1301-1311.