Abstract
Objectives
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.
Methods
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%.
Results
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).
Conclusion
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.
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.
Methods
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%.
Results
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).
Conclusion
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.
| Original language | English |
|---|---|
| Journal | Clinical Microbiology and Infection |
| Early online date | 27 Jul 2023 |
| DOIs | |
| Publication status | Early online date - 27 Jul 2023 |