To determine whether early switch to oral antibiotic treatment in adults with neutropenic sepsis at low risk of complications, is non-inferior to switching later.
This non-inferiority, parallel group, randomized, open-label clinical trial enrolled UK adults hospitalized with neutropenic sepsis.
Participants were randomly assigned to either switch to oral ciprofloxacin plus co-amoxiclav within 12-24 hours or to continue intravenous treatment for at least 48 hours. The primary outcome was a composite measure of treatment failure, 14 days after randomization. The non-inferiority margin was 15%.
There were 129 participants from 16 centres and 125 were assessed for the primary outcome. Of these, 113 patients completed protocolized treatment and comprised the per protocol population. In total, 9 of 64 patients (14·1%) in the standard care arm met the primary endpoint, compared with 15 of 61 (24.6%) in the early switch arm, giving a risk difference of 10·5% (1-sided 95% CI, -∞% to 22%; P=0·14). In the per protocol population, 8 of the 60 patients (13·3%) in the standard care arm met the primary endpoint, compared with 9 of 53 (17%) in the intervention arm giving a risk difference of 3·7% (1-sided 95% CI, -∞% to 14·8%; P=0·59). Duration of hospital stay was shorter in the intervention arm (median 2 [IQR 2,3] vs. 3 days [IQR 2,4]; P=0·002).
While non-inferiority of early oral switch was found in the per protocol population, the intervention was not non-inferior in the intent to treat population.