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 multicenter phase 3 RCT (n=7667), providing a rapid procalcitonin test alongside NEWS2 did not change 3-hour IV antibiotic initiation but reduced 28-day mortality (13.6% vs 16.6%). Clinicians considered the procalcitonin result in about two-thirds of cases, and adverse events were similar between groups.

Key Findings

• No difference in IV antibiotic initiation at 3 hours (48.4% vs 48.2%; p=0.95).
• Lower 28-day mortality with procalcitonin-guided care (13.6% vs 16.6%; adjusted risk difference -3.12 percentage points; 90% CI -4.68 to -1.57).
• Procalcitonin results were considered in 64.7% of cases; adverse events were similar between groups.

Clinical Implications

Integrating rapid procalcitonin testing with NEWS2 may improve risk recognition and outcomes in suspected sepsis triage without delaying antibiotics. Implementation science, workflow integration, and stewardship impacts warrant further evaluation.

Limitations

• Open-label design with clinician discretion; algorithm was guidance-only and used variably (~65%)
• Mechanism for mortality reduction unclear; conducted within UK EDs which may limit generalizability

Future Directions

Elucidate mechanisms of mortality benefit, assess stewardship outcomes (e.g., antibiotic duration, de-escalation), and evaluate implementation and cost-effectiveness across diverse ED settings.