Every day in UK intensive care units, doctors decide how long to keep sepsis patients on antibiotics, balancing the need to clear infection against the risk of drug resistance and side effects. This trial tests whether a fixed five-day course of initial antibiotics works as well as the current variable-length approach, which often extends treatment for much longer. Sepsis kills tens of thousands of people annually in the UK, and overuse of antibiotics fuels the global crisis of antimicrobial resistance. If a shorter course proves safe—meaning it does not increase deaths or relapse rates—the change could transform standard practice across the NHS. Fewer antibiotic days would mean less diarrhoea, kidney injury, and drug-resistant infections for patients, shorter hospital stays, and significant cost savings for the health service. The trial also includes a process evaluation to understand what helps or hinders implementing a shorter regimen in real-world critical care settings. Results will feed directly into UK and international sepsis guidelines, potentially reshaping how millions of patients are treated worldwide.
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Research question: Can antibiotic exposure in critically ill patients with sepsis be reduced by safely shortening the duration of the initial course of antibiotics? Design: A pragmatic, open-label, multi-centre, parallel arm, non-inferiority randomised controlled trial, with an embedded process evaluation. Setting: 50 UK general adult critical care units (ICU and HDU). Target population: Adult patients with suspected or confirmed sepsis who require admission to a critical care unit. Inclusion criteria: Adult patients treated within a critical care setting for sepsis; evidence of organ dysfunction secondary to suspected or confirmed infection; antibiotics initiated for sepsis. Exclusion criteria: Pre-existing immunosuppression; blood neutrophil count less than 500 cells/microlitre; infection source where usual practice involves more than 14 days of antibiotics; patient not expected to survive due to treatment futility. Health technology being assessed: 5-day course of initial antibiotic treatment for sepsis. Measurement of outcomes and cost: Co-primary outcomes: 28-day all-cause mortality as primary safety outcome; total antibiotic treatment days to 28 days as primary effectiveness outcome. Secondary outcomes: 90-day all-cause mortality; adverse events; length of critical care unit stay; length of hospital stay; further infection requiring additional antibiotic use; readmission to critical care unit; in-trial cost effectiveness. Process evaluation: Explore the processes involved in intervention delivery and identify factors and mechanisms that impact trial outcomes. Sample size: A total sample size of 2244 patients will have 90% power, with a one-sided alpha of 2.5%, to demonstrate non-inferiority with a margin of 6% for 28-day mortality, allowing for a 5% dropout rate. The same sample size has 90% power to detect superiority of 1.1 days in total antibiotic treatment days to 28 days. Project timeline: The project will commence on the 1st February 2023. Following regulatory approvals and site set up, patient recruitment will span 26 months. An internal pilot will run during the first 12 months of recruitment. The total project duration is 43 months. Anticipated impact and dissemination: If antibiotic duration can be safely shortened in patients with sepsis, then we anticipate there will be significant reductions in antibiotic use, antibiotic-associated harms and costs. Our results will be widely publicised through open-access peer reviewed journals, PPI groups and the media. We anticipate that the findings of this trial will be incorporated into UK and international sepsis guidelines.
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