A Multicentre Randomised Controlled Trial Assessing the Efficacy of Antimicrobial Prophylaxis for Extracorporeal Shock Wave Lithotripsy in Reducing Urinary Tract Infection (APPEAL): Statistical Analysis Plan and Methodology

Abstract Background Urinary tract infection (UTI) is a recognized complication of shock wave lithotripsy (SWL) for urolithiasis. Evidence guiding antibiotic prophylaxis remains of low certainty, contributing to substantial practice variation and conflicting guidelines. A well-powered, blinded randomized trial is essential to provide trustworthy evidence for clinical practice. Study Design An international, multicentre, randomized controlled trial (the APPEAL trial) assessing the benefits and harms of a single dose of ciprofloxacin versus placebo before SWL in reducing post-procedure UTI. Patients, healthcare providers, data collectors, outcome adjudicators and statisticians blinded to treatment assignment. Endpoints Appeal’s primary outcome is bacteriuria or symptomatic UTI (symptomatic UTI defined as symptomatic cystitis, pyelonephritis, or urosepsis) within approximately 7-14 days post-SWL. Other outcomes include pyelonephritis or urosepsis, and serious adverse events. Patients and Methods Over 1,500 patients from high- and middle-income countries undergoing SWL for nephrolithiasis or ureterolithiasis. Exclusion criteria include a positive pre-SWL urine analysis for nitrites or urine culture, ongoing or planned antibiotic use, suspected struvite stones, urinary catheters or diversion, or a history of urosepsis. Imminent report of APPEAL will provide high-quality evidence on the role of antibiotic prophylaxis in SWL and identify subgroups that may benefit most. Trial Registration ClinicalTrial.gov identifier (ID): NCT03692715 .