Procalcitonin testing combined with NEWS2 evaluation compared with usual care based on NEWS2 for identification of sepsis and antibiotic initiation in the emergency department in England and Wales (PRONTO): a multicentre, randomised, controlled, open-label, phase 3 trial.

Summary

In a 20-ED, phase 3 randomized trial (n=7667), adding rapid procalcitonin guidance to NEWS2 did not change IV antibiotic initiation by 3 hours but significantly reduced 28-day mortality (13.6% vs 16.6%). Clinicians considered procalcitonin results in 64.7% of cases; adverse events were similar between groups.

Key Findings

• No difference in 3-hour IV antibiotic initiation: 48.4% (PCT-guided) vs 48.2% (usual care).
• Lower 28-day mortality with PCT guidance: 13.6% vs 16.6% (adjusted risk difference -3.12 percentage points; non-inferiority and superiority met).
• Procalcitonin informed clinical decisions in 64.7% of guided cases; adverse events were similar between groups.

Clinical Implications

Emergency departments could adopt procalcitonin-guided algorithms alongside NEWS2 to enhance early risk stratification and potentially reduce mortality, while maintaining timely antibiotic initiation. Implementation should monitor adherence and explore pathways by which mortality improves.

Limitations

• Open-label design with optional adherence to the guidance algorithm.
• Unclear mechanism underlying mortality benefit; no reduction in early antibiotic initiation.

Future Directions

Evaluate implementation fidelity, identify patient subgroups deriving greatest benefit, and elucidate biological/operational mechanisms of mortality reduction; assess integration with other biomarkers and rapid diagnostics.