PRONTO Trial: Procalcitonin Plus NEWS2 in ED Suspected Sepsis

The PRONTO trial reported that adding rapid procalcitonin testing to NEWS2 did not change early intravenous antibiotic use, while 28-day mortality was lower. Investigators described these paired co-primary findings in emergency department patients aged 16 years or older who were managed as suspected sepsis. The results placed an early process measure and a clinical outcome side by side within the same randomized comparison. Researchers assessed whether a biomarker-guided approach influenced care after triage. The comparison evaluated rapid procalcitonin testing plus NEWS2 assessment using a guidance-only algorithm versus usual care based on NEWS2 in this emergency department population.

The study used a multicentre, individually randomized, open-label, phase 3 design across 20 emergency departments in England and Wales. Researchers enrolled patients aged 16 years or older who presented with suspected sepsis and assigned them 1:1 through a centrally controlled web-based program. Usual care relied on NEWS2, while the intervention paired NEWS2 with rapid procalcitonin testing in a guidance-only algorithm for clinicians. The authors defined co-primary endpoints as intravenous antibiotic initiation at 3 hours, assessed for superiority, and 28-day mortality from triage assessment, assessed in a non-inferiority framework. This setup separated an early treatment process measure from a mortality outcome within prespecified analytic approaches.

For the early antibiotic endpoint, intravenous antibiotic initiation at 3 hours was similar between groups: 48.4% with rapid procalcitonin testing versus 48.2% with usual care. The adjusted risk difference was -0.08 percentage points (p=0.95), and investigators reported no between-group difference. Clinicians considered the procalcitonin result in decision-making for 64.7% of participants in the intervention group. This reflects how often the test informed clinician assessment within the intervention arm. In the trial report, the neutral antibiotic finding and partial use of the test were presented as key features of the intervention arm.

Investigators reported 28-day mortality of 13.6% in the procalcitonin-guided group and 16.6% with usual care. The adjusted risk difference was -3.12 percentage points, and the upper bound of the 90% confidence interval remained below the prespecified 2.5% non-inferiority margin. Researchers also noted that the confidence interval lay below the point of no effect. This was the trial’s reported mortality finding within its prespecified analytic framework.

The authors stated that planned subgroup, sensitivity, and secondary analyses did not account for the mortality finding. They recorded 180 adverse events across the study during the periods participants were included. Investigators also reported one serious adverse event that they judged probably or definitely attributable to the procalcitonin test. No additional explanatory signal was identified in the prespecified analyses presented with the main results.

Key Takeaways

• The trial reported no difference in intravenous antibiotic initiation at 3 hours between groups.
• Lower 28-day mortality was observed in the procalcitonin-guided group within the trial's non-inferiority framework.
• Clinicians considered the procalcitonin result in about two-thirds (64.7%) of intervention participants.
• The authors reported one serious adverse event probably or definitely attributable to the procalcitonin test, and planned analyses did not explain the observed mortality difference.