Early Discontinuation versus Continuation of Antimicrobial Therapy in Low Risk Pediatric Cancer Patients with Febrile Neutropenia, Before Recovery of Counts: A Randomized Controlled Trial (DALFEN Study)

Abstract

Objective To determine if early discontinuation of antimicrobials in pediatric patients with low risk febrile neutropenia is as effective as continuing therapy before recovery of counts, in an outpatient setting. Methods In an open label, non-inferiority, randomized controlled phase 3 trial at a tertiary cancer center, patients aged 3–18 y, with low risk febrile neutropenia were started on empirical intra-venous antibiotics in an outpatient setting. Randomization was done when the patients became afebrile for at least 24 h; standard arm consisted of oral antibiotics, while antibiotics were stopped in the experimental arm. Enrolled patients were followed for re-appearance of fever and rate of re-admission, until ANC ≥ 500. A pilot feasibility randomized study with similar design preceded this trial. Results From Jan 2017-Dec 2018, 75 patients were randomized: 38 to stoppage arm while 37 patients received oral antibiotics. Baseline characteristics were equally matched. Success rates were 94.6% in the continuation arm vs. 94.7% in the stoppage arm; absolute risk difference was 0.1% (95% CI: −10.0% to +10.3%), thus suggesting that the experimental arm is non-inferior to the standard arm. There was no re-admission on failure in any arm. Conclusions Antimicrobial therapy in low risk afebrile neutropenic patients can be stopped early. This approach can lead to significant cost and resource benefits.