ProMISe Trial

NEJM

April 2, 2015

Trial of Early, Goal-Directed Resuscitation for Septic Shock.

Summarized by: 

Mazen Kherallah

What was the research question?

  • Does early goal-directed therapy (EGDT) compared with standard therapy reduce mortality at 90 days in adult patients with septic shock?


How did they do it?

  • A pragmatic randomized trial with an integrated cost-effectiveness analysis in 56 hospitals in England.

  • 1260 patients were randomized to receive EGDT (630 patients) or usual care (630 patients).

  • The primary clinical outcome was all-cause mortality at 90 days.


What did they find?

  • 90-day mortality was not significantly different in the EGDT group compared to usual care (29.5% vs. 29.2%, P=0.90).

  • EGDT had an increased treatment intensity indicated by increased use of intravenous fluids, vasoactive drugs, and red-cell transfusions.

  • Patients in the EGDT group had significantly worse organ-failure scores at 6 hours but not at 72 hours (SOFA at 6 hours: 6.4 vs. 5.6, P<0.001), more advanced cardiovascular support (37% vs. 30.9, P=0.026), and longer stays in the intensive care unit (ICU: 2.6 vs 2.2 days p=0.005).

  • There were no significant differences in any other secondary outcomes, including requirement of respiratory support, receipt of renal support, median stay in ER or the hospital, death at 28 days or hospital discharge, health-related quality of life, or in rates of serious adverse events.

  • On average, EGDT increased costs, and the probability that it was cost-effective was below 20%.


Are there any limitations?

· Non-blinded trial

· Only one third of eligible patients were recruited.

What does it mean?

· A strict EGDT protocol in patients with septic shock who were resuscitated and received intravenous antibiotics, did not lead to an improvement in outcome.

· No need to follow strict EGDT if adequate fluid resuscitation and early use of antimicrobial therapy were implemented.

ProMISe Trial