Two vs. three weeks of treatment with amoxicillin-clavulanate for stabilized community-acquired complicated parapneumonic effusions. A preliminary non-inferiority, double-blind, randomized, controlled trial

Abstract

Background: The optimal duration of antibiotic treatment for complicated parapneumonic effusions (CPPEs) has not been properly defined. Our aim was to compare the efficacy of amoxicillin-clavulanate for 2 vs. 3weeks in patients with CPPE (i.e. those which required chest tube drainage). Methods: In this non-inferiority, randomized, double-blind, controlled trial, patients with community-acquired CPPE were recruited from two centers in Spain and, after having obtained clinical stability following 2weeks of amoxicillin-clavulanate, they were randomly assigned to placebo or antibiotic for an additional week. The primary objective was clinical success, tested for a non-inferiority margin of<10%. Secondary outcomes were the proportion of residual pleural thickening of>10mm at 3months, and adverse events. The study was registered with EudraCT, number 2014-003137-25. We originally planned to randomly assign 284 patients. Results: After recruiting 55 patients, the study was terminated early owing to slow enrolment. A total of 25 patients were assigned to 2weeks and 30 patients to 3weeks of amoxicillin-clavulanate. Clinical success occurred in the 25 (100%) patients treated for 2weeks and 29 (97%) treated for 3weeks (difference 3%, 95% CI -3 to 9.7%). Respective between-group differences in the rate of residual pleural thickening (-12%, 95%CI -39 to 14%) and adverse events (-7%, 95%CI -16 to 2%) did not reach statistical significance. Conclusions: In this small series of selected adult patients with community-acquired CPPE, amoxicillin-clavulanate treatment could be safely discontinued by day 14 if clinical stability was obtained.