PRONTO

PROcalcitonin and NEWS2 evaluation for Timely identification of sepsis and Optimal use of antibiotics in the Emergency Department.

Watch a video of the PRONTO trial on YouTube

Background

Sepsis is a common, potentially life-threatening complication of infection. The optimal treatment for sepsis includes early recognition, prompt antibiotics and fluids into a vein (intravenous/IV). Currently, clinicians assess severity in patients in the Emergency Department (ED) with a scoring system based on simple to measure observations: the National Early Warning Score (NEWS). NEWS helps clinicians identify the sickest patients. It is not specific and tends to over-diagnose sepsis leading to over prescribing of antibiotics and promoting antimicrobial resistance. It is the best we have and currently used in over 70% of English hospitals.

Adults with suspected sepsis fall into one of three categories:

a) those looking ill needing urgent IV antibiotics and fluids within 1 hour,

b) those that are unwell, but will not come to harm if IV antibiotics are not administered within 1 hour, allowing time for further assessment prior to starting antibiotics within 3 hours

c) those not critically unwell who may or may not need IV antibiotics.

Procalcitonin (PCT), a blood test not widely used in the NHS, helps to identify bacterial infection. The National Institute for Health and Care Excellence (NICE) recommended further research on PCT testing in EDs for guiding antibiotic use in people with suspected sepsis.

Research aim

The primary aim is to compare PCT- supported assessment with standard care of suspected sepsis in adults presenting to the ED, and measure whether this approach reduces prescriptions of antibiotics without increasing mortality by decreasing uncertainty in the group who may not need IV antibiotics urgently within 1 hour, or not need antibiotics at all.

Study design

The evaluation will be done via a randomised controlled trial in ten hospitals. Adult patients with suspected sepsis presenting to the ED will be randomly assigned to current standard of care or PCT- supported care. In the PCT arm, a bedside test (taking 20 minutes) is performed plus the NEWS assessment.  Depending on the result of the PCT plus the NEWS, patients will receive IV antibiotics and fluids within the current recommended time frame depending on severity (see study flow chart).  Doctors and patients will know what treatment arm they are in. Doctors remain free to use antibiotics outside the study guidelines using their clinical judgement in any of the risk groups. The key outcome measures will be whether IV antibiotics are started, and death within 28 days. An analysis will be done to understand how well clinicians follow the recommendations, ease of use of the additional test in a busy ED, and its cost effectiveness. A sample of patients interviewed at 90 days follow up will assess experiences of care.

Patient and Public Involvement

The UK Sepsis Trust (UKST) were consulted. This application includes JC as a patient representative, sepsis survivor and UKST volunteer. JC contributed to all parts of the study proposal. A sepsis patient focus group has been involved in a wider consultation on the study design, patient acceptability, patient perceptions of antibiotic therapy in sepsis management and the risks of antimicrobial resistance.

Potential impact

If the study shows that PCT-supported assessment is superior to current practice, then it will lead to better outcomes in sepsis, improved care and a reduction in inappropriate antibiotics prescriptions.

Results

Expected publication date of main results will be June 2024.