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 5453 analyzed patients, procalcitonin-guided care did not change 3-hour IV antibiotic initiation versus usual care (~48% in both) but significantly reduced 28-day mortality (13.6% vs 16.6%; adjusted risk difference −3.12 percentage points), meeting both non-inferiority and superiority criteria. Adverse events were similar and clinicians considered the procalcitonin result in about two-thirds of cases.

Key Findings

• 3-hour IV antibiotic initiation was similar between groups (48.4% procalcitonin-guided vs 48.2% usual care).
• 28-day mortality was lower with procalcitonin-guided care (13.6% vs 16.6%; adjusted risk difference −3.12 percentage points, meeting non-inferiority and superiority).
• Adverse events were comparable, and the procalcitonin result was considered in 64.7% of guided-care decisions.

Clinical Implications

Emergency departments should consider integrating rapid procalcitonin testing into sepsis pathways alongside NEWS2. Implementation should focus on workflow integration and clinician adherence to guidance while monitoring antibiotic stewardship and mortality outcomes.

Limitations

• Open-label design with potential performance bias and variable adherence to the guidance algorithm
• No reduction in early antibiotic initiation; mechanisms for mortality benefit require further study

Future Directions

Identify mechanisms underpinning mortality reduction, define subgroups that benefit most, and evaluate implementation strategies and cost-effectiveness across diverse ED settings.