Background and Rationale
Vesicoureteral Reflux (VUR), the retrograde flow of urine from the bladder to the ureters, is the most common functional abnormality of the urinary tract in children. VUR is found in 30-50% of children with a urinary tract infection (UTI).
The goal of current management of VUR has been to prevent UTIs, theoretically decreasing the risk of permanent renal scarring. Renal scarring has been associated with proteinuria, hypertension, eclampsia, and end-stage renal disease (ESRD) in later life. Most children with VUR outgrow it by adolescence. Current management consists of either long-term antimicrobial prophylaxis while VUR is present or surgical correction.
The current management of VUR has been based on an international study, which compared antimicrobials vs. surgery but did not include a control group. Because of this design flaw, the need for either antimicrobial prophylaxis or surgery in all children with VUR has recently been questioned. The cost and potential harm of current diagnostic and therapeutic studies to detect VUR as well as the development of antimicrobial resistance, resulting from the long term use of prophylactic antibiotics has also caused concern.
A great need exists for evidence-based recommendations for the management of children with VUR.
Specific Aim of the Study
This is a multicenter, randomized, double-blind, placebo-controlled study to determine if daily antimicrobial prophylaxis, in the setting of prompt evaluation and treatment of UTI, is superior to placebo in preventing recurrence UTI and/or the occurrence of, or worsening, of renal scarring in children with vesicoureteral reflux (VUR).
Six hundred children diagnosed with VUR will be recruited from across the United States and Canada after their first UTI. They will be followed for 2 years in one of two double blinded treatment arms, antimicrobial prophylaxis or placebo.
The primary study endpoint is recurrent urinary tract infection. Secondary endpoints include renal scarring and development of antimicrobial resistance.