SHORTER trial: protocol for a pragmatic, multicentre, randomised controlled trial of short-duration antibiotic therapy for critically ill patients with sepsis.

INTRODUCTION

Sepsis is a life-threatening syndrome resulting from a dysregulated immune response to an infection. Patients with sepsis can become critically ill and require advanced organ support in a hospital critical care setting. Antibiotics are lifesaving in sepsis, but overuse is associated with harm and promotes antimicrobial resistance, a rising global challenge making antibiotic treatment less effective. The prevalence of antibiotic use is very high in patients admitted to critical care. Research indicates that shorter courses of antibiotics are as effective as longer durations in the treatment of certain infections, but uncertainty remains for patients with sepsis. The aim of SHORTER is to investigate whether treating critically ill patients with suspected or confirmed sepsis with a fixed 5-day, short course of antibiotics is clinically and cost-effective compared with standard of care.

METHODS AND ANALYSIS: SHORTER is a pragmatic, multicentre, randomised controlled trial. 2244 adults treated with antibiotics for suspected or confirmed sepsis in a critical care setting will be recruited from 50 UK National Health Service hospitals. Participants will be randomised to either a fixed 5-day index course of antibiotics (intervention) or standard of care duration antibiotics (control). The coprimary outcomes are 28-day mortality (non-inferiority) and antibiotic treatment days (superiority). Secondary outcomes will assess the effect of short-duration antibiotic therapy on 90-day mortality, hospital readmissions, further infection rates and health economic impacts. A process evaluation will be embedded in the trial.

ETHICS AND DISSEMINATION: Favourable ethical opinion has been received from the Wales Research Ethics Committee 4 (Ref: 23/WA/0197) and Scotland A REC (Ref: 24/SS/0013). Results will be publicly disseminated via Patient Public Involvement and Engagement representatives, charities and media, and to the clinical community via professional societies, peer-reviewed publications and conference presentations.

TRIAL REGISTRATION NUMBER: ISRCTN40090372.