Mortality in the Sepsis-3 Era: A Systematic Review of Multicenter Randomized Controlled Trials.
Marko Nemet, Ibrahim Serhat Karakus, Cameron Gray Gmehlin et al.
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In 30 seconds
This systematic review assessed multicenter randomized controlled trials published since 2016 that tested pharmaceutical or mechanistic interventions in adults with Sepsis-3 sepsis or septic shock and reported mortality. Across 31 trials involving over 7,000 patients at 550 centers, only four reported a mortality benefit: three Chinese studies of herbal anti-inflammatory compounds or aminophylline, and one European study of corticosteroids in vasopressor-dependent septic shock. The other 27 trials found no mortality benefit. Median mortality was 31.6% (interquartile range 24.1-45.5) in control arms and 35.4% (interquartile range 25.7-49.6) in intervention arms.
Key findings
- Only four of 31 multicenter randomized trials reported a mortality benefit; 27 reported none.
- The review included over 7,000 patients across 550 centers.
- Median mortality was 31.6% (interquartile range 24.1-45.5) in control arms and 35.4% (interquartile range 25.7-49.6) in intervention arms.
- The four positive trials comprised three studies from China and one European corticosteroid study in vasopressor-dependent septic shock.
Why it matters
The review highlights how rarely interventions tested in multicenter sepsis trials have demonstrated mortality benefit, despite substantial research activity. The variation in patient populations, sepsis definitions, and outcome reporting also complicates comparisons across trials. These findings underscore the importance of careful trial design and patient selection, alongside outcomes that capture more than mortality.
What to keep in mind
The review reports substantial heterogeneity in patient populations, sepsis definitions, and outcome reporting, limiting comparability across trials.