Individualised versus standard duration of antibiotic therapy in children with acute uncomplicated febrile urinary tract infection: a study protocol and statistical analysis plan for a multicentre randomised clinical trial

INTRODUCTION: Febrile urinary tract infection is one of the most common bacterial infections in children. Currently, recommended antibiotic duration is 10 days. However, recent evidence suggests that 90%-95% of children with febrile urinary tract infections are afebrile and clinically improved 48-72 hours after treatment initiation. Accordingly, individualised duration of antibiotic therapy, according to the recovery time, might be more beneficial than current recommendations, but no evidence exists.

METHODS AND ANALYSIS: An open-label randomised clinical trial equally randomising children aged 3 months to 12 years from eight Danish paediatric departments with uncomplicated febrile (≥38°C) urinary tract infection to either individualised or standard duration of antibiotic therapy. Children allocated to individualised duration of antibiotic therapy will terminate antibiotic therapy 3 days after clinical improvement with no fever, flank pain or dysuria. Children allocated to standard duration will receive 10 days of antibiotic therapy. Co-primary outcomes are non-inferiority for recurrent urinary tract infection or death within 28 days after the end of treatment (non-inferiority margin 7.5 percentage points) and superiority for the number of days with antibiotic therapy within 28 days after treatment initiation. Seven other outcomes will also be assessed. A total of 408 participants are needed to detect non-inferiority (one-sided alpha 2.5%; beta 80%).

ETHICS AND DISSEMINATION: This trial has been approved by the Ethics Committee (H-21057310) and the Data Protection Agency (P-2022-68) in Denmark. Regardless of the trial's findings (whether positive, negative or inconclusive), the results will be compiled into one or more manuscripts for publication in international peer-reviewed scientific journals and presented at conferences.

TRIAL REGISTRATION NUMBER: NCT05301023.