Antibiotic Stewardship in Suspected Neutropenic Fever (ASTERIC Trial)

Executive Summary Background: Neutropenic Fever (NF), or febrile neutropenia, occurs in patients with early stage and metastatic solid tumours, non-leukaemic haematological cancers and acute leukaemia. It has a crude mortality rate of 3 to 18%. In Hong Kong, and in line with international guidelines, the target time from ED registration to ultra-broad spectrum antibiotic (UBSA) administration (door-to-antibiotic time, DTA time) is one hour disregarding the absolute neutrophil count (ANC). However, over 80% patients presenting to hospital with suspected NF (sNF) do not have NF and do not require UBSAs. Thus there is a need for evidence for a safe role for early treatments in patients with sNF to reduce unnecessary use of antibiotics. Protocol, Eligibility and Randomisation: This protocol describes the ASTERIC Trial, a pragmatic, multi-centre, type 1, hybrid effectiveness-implementation, stepped-wedge, before and after, cluster randomised controlled trial with variable baseline and follow up periods. Hospitals will be randomised to start dates comparing usual standard of care (SoC) (Period 1, before) with a new antibiotic stewardship protocol (Period 2, after). Hospitals, not patients, are randomised to variable start dates. The evidence for starting early UBSAs in patients with NF is well-established. What is unclear is how to optimise personalised care and the start times of UBSA when the majority of sNF patients do not have NF, there are delays to receiving an ANC report, and a proportion of patients might not need hospital admission. Study design: a multi-centre, hybrid type 1 effectiveness-implementation trial which is an appropriate study design to evaluate the real-world effectiveness of an antibiotic stewardship protocol; and the barriers to and facilitators of its implementation in the ED setting. Settings: Eight hospitals in Hong Kong with patient involvement 24/7. Outcomes: The Trial has two co-primary outcomes 1) mean total dose of UBSAs prescribed in