Abstract 1704P
Background
Neutropenic sepsis (NS) is common after systemic anticancer therapy (SACT). Consensus guidelines recommend switching from intravenous (IV) to oral antibiotics after 48 hours of IV therapy but evidence is lacking on earlier switch.
Methods
EASI-SWITCH is a randomised multicentre noninferiority trial to assess effectiveness of early switch from IV to oral antibiotics in low-risk NS. Target sample size (n=230) assumed a 15% treatment failure rate (TFR) and a 15% non-inferiority margin. Adults with fever ≥380C, neutrophil count ≤1.0x109/l, MASCC score ≥21 and receiving IV piperacillin/tazobactam or meropenem were eligible. Intervention comprised switch to oral ciprofloxacin and co-amoxiclav ≤24 hours of starting IV antibiotics; control comprised ongoing IV therapy for ≥48 hours (further therapy physician-choice). The primary outcome was treatment failure, a composite measure of fever persistence/recurrence after 72 hours, escalation from protocol antibiotics, readmission, critical care support or death. Noninferiority of early switch required the noninferiority test to be met in both intention-to-treat (ITT) and per-protocol (PP) populations.
Results
129 patients were randomized from 2016-2019. In the ITT population, TFR was 14.1% in control and 24.6% in intervention groups, difference 10.5% (95% CI -0.01 to 0.22). In the PP population, TFR was 13.3% in control and 17.0% in intervention groups, difference 3.7% (95% CI -0.07 to 0.148). Overall, noninferiority of the intervention was not proven. Treatment failure was most frequently due to persistence/recurrence of fever and/or escalation from protocolized antibiotics with no critical care admissions or deaths within 14-days. There were no significant differences in adverse events and length of admission between intervention and control groups (mean 2.6 and 3.1 days respectively).
Conclusions
Noninferiority for early oral switch was not proven. Our findings suggest this may be a suitable approach for patients willing to accept a modest increase in risk of treatment failure leading to delayed discharge/re-admission, but with the majority of patients experiencing successful treatment, as well as low risk of severe complications such as critical care admission/death.
Clinical trial identification
EudraCT 2015-002830-35.
Editorial acknowledgement
Legal entity responsible for the study
Belfast HSC Trust.
Funding
National Institute for Health Research (NIHR).
Disclosure
V. Coyle: Financial Interests, Personal, Invited Speaker, Producing Educational Material: Servier; Financial Interests, Institutional, Research Grant, Pre-clinical Research Funding and Support For Clinical Trial: Astex Pharmaceuticals; Other, Hospitality/Conference Attendance Support: Servier. R. Barnes: Financial Interests, Personal, Invited Speaker: Gilead. D. McAuley: Non-Financial Interests, Personal, Leadership Role: National Institute of Health Research EME Programme Director. R. Plummer: Financial Interests, Personal, Advisory Role: Pierre Faber; Financial Interests, Personal, Advisory Role: Bayer; Financial Interests, Personal, Advisory Role: BMS; Financial Interests, Personal, Advisory Role: CV6 Therapeutics; Financial Interests, Personal, Advisory Role: Astex; Financial Interests, Personal, Advisory Role: Sanofi; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Kaurus Therapeutics; Financial Interests, Personal, Advisory Role: Biosceptre. A. Thomas: Financial Interests, Personal, Advisory Role: BMS. R. McMullan: Financial Interests, Personal, Invited Speaker: Gilead. All other authors have declared no conflicts of interest.