This multicenter, randomized, double-blind, placebo-controlled trial was designed to determine whether daily antimicrobial prophylaxis is superior to placebo in preventing recurrence of urinary tract infection (UTI) in children with vesicoureteral reflux (VUR). Patients were randomly assigned to treatment for 2 years with daily antimicrobial prophylaxis (trimethoprim-sulfamethoxazole) or placebo. The study was designed to recruit 600 children (approximately 300 in each treatment group. The protocol encouraged prompt evaluation of children with UTI symptoms and early therapy of culture-proven UTIs. It was expected that approximately 10% of children would have to discontinue study medication due to allergic reactions. Assuming a 20% placebo event rate and 10% non-adherence rate, the study had 83% power to detect an absolute 10% event rate in the antimicrobial prophylaxis group. If the placebo event rate was instead 25%, power was 97% to detect an absolute 10% event rate in the treated group, even if non-adherence were as high as 15%. The primary analysis is intention-to-treat with missing outcome data analyzed as UTI.

In addition to collecting follow-up data on urinary tract infections, renal scarring and antimicrobial resistance, quality of life, medication adherence, safety parameters, utilization of health resources, and change in VUR were assessed periodically throughout the study.

Urinary tract infection recurrence; Renal scarring; antimicrobial resistance

Diagnosed first or second febrile or symptomatic UTI within 112 days prior to randomization; Presence of Grade I- IV VUR based on radiographic VCUG performed within 112 days of diagnosis of index UTI.

Among children with vesicoureteral reflux after urinary tract infection, antimicrobial prophylaxis was associated with a substantially reduced risk of recurrence but not of renal scarring.