ProMISe
Trial of early, goal-directed resuscitation for septic shock
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Overview
In early septic shock, a 6-hour EGDT protocol did not improve 90-day mortality versus usual care.
Clinical takeaway
ProMISe showed that once patients with septic shock were identified early and given antibiotics and adequate fluids, a strict 6-hour EGDT protocol added intensity and cost without improving outcome.
Key result
90-day mortality was 29.5% with EGDT vs 29.2% with usual care (RR 1.01; 95% CI 0.85-1.20; p=0.90).
Practice impact
Supports early septic-shock care without a mandatory EGDT protocol.
Evidence
Study design
Pragmatic randomized trial with an integrated cost-effectiveness analysis in 56 hospitals in England.
Enrollment
1,260
Follow-up
All-cause mortality at 90 days.
Geography
England
Clinical question
Does a 6-hour EGDT protocol improve 90-day mortality compared with usual care in early septic shock?
Population
- Patients with septic shock who were identified early.
Intervention
EGDT as a 6-hour resuscitation protocol.
Comparator
Usual care.
Primary outcome
All-cause mortality at 90 days.
A strict 6-hour EGDT protocol did not improve 90-day survival over usual care in early septic shock.
Relative risk / 1.01 / 95% CI 0.85-1.20 / p=0.90
Key results
- 90-day mortality: 29.5% with EGDT vs 29.2% with usual care; relative risk 1.01 (95% CI 0.85-1.20; p=0.90).
- Absolute risk reduction with EGDT was -0.3 percentage points (95% CI -5.4 to 4.7).
- EGDT increased intravenous fluids, vasoactive drugs, red-cell transfusions, days of advanced cardiovascular support, and ICU length of stay.
- Serious adverse events did not differ, but EGDT increased costs and had a less than 20% probability of being cost-effective.
Harms
- EGDT produced worse organ-failure scores, more days of advanced cardiovascular support, and longer ICU stays.
- Rates of serious adverse events did not differ between groups.
Clinical Use
Practice impact
- Supports early septic-shock care without a mandatory EGDT protocol.
Applicability
- Most applicable to patients with septic shock identified early and already receiving intravenous antibiotics and adequate fluid resuscitation.
Limitations
- The trial tested EGDT after early antibiotics and adequate fluids, not resuscitation versus neglect.
- Increased treatment intensity in the EGDT arm was accompanied by worse organ-failure scores, which may reflect protocol-driven care rather than a true harm signal.
Common misinterpretations
- ProMISe refutes a mandatory EGDT protocol, not the value of early identification, antibiotics, and fluids.
- A negative clinical result plus higher cost means the protocol is not required, not that septic-shock care can be delayed.
Citation
Mouncey PR, Osborn TM, Power GS, et al. Trial of early, goal-directed resuscitation for septic shock. N Engl J Med. 2015;372(14):1301-1311. doi:10.1056/NEJMoa1500896
In patients with septic shock who were identified early and received intravenous antibiotics and adequate fluid resuscitation, hemodynamic management according to a strict EGDT protocol did not lead to an improvement in outcome.
- PMID
- 25776532