Cefalexin for UTIs – Right treatment Length in Young children (the CURLY trial). A multi-centre, randomised trial to determine the optimal duration of cefalexin therapy for the treatment of febrile urinary tract infections in children

Research Question In infants and young children with a clinical diagnosis of febrile urinary tract infection (UTI), what is the optimal duration of oral cefalexin treatment? Background Cefalexin is the NICE-recommended first-line oral antibiotic for children and young people with a febrile UTI, but there is limited evidence for its optimal duration. This is highlighted as a research priority in national guidelines, and is of particular importance given the high incidence of the condition and the increasing emergence of multidrug-resistant organisms. Aim To evaluate the efficacy, safety, and effect on bacterial resistance of five cefalexin treatment durations in children with febrile UTIs. Primary Objectives To determine the optimal cefalexin duration (the shortest effective treatment duration) for the treatment of febrile UTIs in children, to achieve clinical cure. Secondary Objectives To assess the impact of cefalexin treatment duration on (1) UTI recurrence, (2) microbiological cure and antimicrobial resistance, (3) antibiotic-associated adverse events, (4) adherence, (5) quality of life, and (6) cost-effectiveness. Design Open label, multi-arm “DURATIONS” design RCT in 8 paediatric emergency departments across the UK, with a 6-month internal pilot. This will produce a “cefalexin duration vs cure rate” curve, to determine the optimal number of treatment days. Participants Infants and children with a clinical diagnosis of febrile UTI (defined clinical features and point-of-care urine testing suggesting a likely UTI) in whom the decision has been made to treat with oral cefalexin. Interventions Central randomisation in 1:1:1:1:1 ratio to one of 5 cefalexin course durations (3, 5, 6, 8 or 10 days). Cefalexin will be administered as a standard proprietary liquid suspension at a standard recommended dose. Outcomes Primary: Clinical UTI cure, defined as patients in whom there is (i) fever resolution and (ii) no additional systemic antibiotic prescription by 16 days post-randomisation. Secondary: UTI recurrence; Microbiological cure; Antimicrobial resistance (comparison of the antibiotic sensitivities of pre- and post-treatment urine samples along with the identification of ESBL-producing organisms); Antibiotic-associated adverse events; Adherence to trial medication; Quality of life (CHU9D). Follow up to 30 days (+/- 2 days) post-randomisation. Health economic outcomes and consent for future antimicrobial resistance and genomic studies on stored samples and data linkage studies for long term outcomes. Sample size A sample size of 500 microbiologically-confirmed participants is required. This is inflated to 705 after allowing for 12% with non-proven UTI culture, 10% with cefalexin-resistant UTI and 10% loss to follow up. Timelines 8 months setup,16 months recruitment and follow-up (pilot phase 6 months, main phase 10 months), 6 months for final analysis, write up and data sharing preparation/archiving. Impact & Dissemination Findings will have direct and immediate application to clinical practice. Results will be presented at conferences, published in journals, and made available via open-source methods. Patient Involvement We have co-produced this application with children and their families. We are committed to work in partnership with families to deliver and disseminate this research to ensure that it has maximum impact.