PRONTO Trial Finds Mortality Drop With Procalcitonin Plus NEWS2
Key Takeaways
- Twenty-eight-day mortality in patients with suspected sepsis was lower in the procalcitonin-guided group than in the usual-care group.
- Intravenous antibiotic initiation at 3 hours was similar in the two groups.
PRONTO was a multicenter, open-label, individually randomized phase 3 trial conducted in 20 hospital emergency departments within 17 NHS Trusts or Health Boards across England and Wales. It enrolled patients aged 16 years or older with suspected sepsis and randomly assigned 7667 participants in a 1:1 ratio. Of those, 3836 entered NEWS2-based usual care and 3831 entered rapid procalcitonin testing plus NEWS2 within a guidance-only algorithm, with 5453 included in the primary analysis population. In the intervention group, clinicians considered the procalcitonin result in 64.7% (1771/2738) of participants, and clinicians in both groups could use, ignore, or deviate from the algorithm.
The trial used co-primary endpoints of intravenous antibiotic initiation at 3 hours and 28-day mortality after triage assessment. Intravenous antibiotics were started by 3 hours in 48.4% (1325/2738) of procalcitonin-guided participants and 48.2% (1308/2715) with usual care. The adjusted risk difference was -0.08 percentage points, with a 95% CI of -2.58 to 2.42 and p=0.95.
Mortality was 13.6% (372/2738) in the procalcitonin-guided group and 16.6% (450/2715) with usual care, an adjusted risk difference of -3.12 percentage points. The upper bound of the 90% CI was below the 2.5 percentage-point non-inferiority margin and below the point of no effect.
Across the study, 180 adverse events were recorded, including 96 events in 57 participants (1.9%) in usual care and 84 events in 66 participants (2.2%) in procalcitonin-guided care. One serious adverse event, reported among fewer than 1% of 2042 participants in the procalcitonin-guided group, was considered probably or definitely attributable to the test.