A Randomized Controlled Trial on Antibiotic Prophylaxis in Children With Vesico-Ureteral Reflux
A Randomized Controlled Trial on Antibiotic Prophylaxis in Children With Vesico-Ureteral Reflux
The aim of this study is to assess the effectiveness of antibiotic prophylaxis in preventing
 pyelonephritis and in avoiding the appearance of new scars in a sample of children under 36
 months with vesico-ureteral reflux (VUR).
In recent years, the effectiveness of continuous antibiotic prophylaxis in children with
 vesico-ureteral reflux (VUR) has been intensely discussed. The question is not only whether
 antibiotics are effective in preventing recurrent urinary tract infections (UTI), but also
 whether they alter the natural history of disease and help to prevent the appearance of new
 kidneys scars. The evidence on the effectiveness of antibiotic prophylaxis is scanty:
 randomised controlled trials (RCT) published until now are poorly designed and carried out in
 very heterogeneous samples of children, i.e. spanning from 6 months to 14-18 years of age and
 pooling patients with and without VUR. A recently updated Cochrane Systematic Review
 concludes that high quality RCTs are needed to determine the effectiveness of long-term
 antibiotics for the prevention of UTIs in susceptible children. Moreover, the presence of VUR
 has not been firmly shown to be a risk factor for recurrence of pyelonephritis, and a direct
 association between VUR and the presence of scars or the appearance of new scars has not been
 demonstrated; there is just an association between VUR of grade IV-V and prenatal renal
 dysplasia, almost exclusively in male infants. In spite of this uncertainty, several practice
 guidelines recommend long term antibiotic prophylaxis in children with different degrees of
 VUR.

 The aim of this study is to assess the effectiveness of antibiotic prophylaxis in preventing
 pyelonephritis and in avoiding the appearance of new scars in a sample of children under 36
 months with VUR.

 Comparison: In a multicentre trial, 100 patients with VUR diagnosed with cystourethrography
 after a first episode of acute pyelonephritis or for prenatal evidence of pyelectasia will be
 assigned randomly to receive prophylaxis or not. Randomization will be carried out using a
 centralized minimization procedure to balance for sex, age group and VUR grade.
Inclusion Criteria:

 -  presence of vesico-ureteral reflux (VUR) grade II, III or IV, based on the
 International Classification, mono or bilateral, diagnosed between one day and 30
 months of age after a first episode of acute pyelonephritis, or after birth during
 diagnostic procedures planned as a consequence of prenatal ultrasonographic evidence
 of pyelectasia.

 Exclusion Criteria:

 -  previous episodes of urinary tract infection (UTI), even if only suspected (e.g. an
 episode of fever treated with antibiotics without performing urine culture);

 -  VUR grade I, because of the high probability of rapid spontaneous resolution;

 -  VUR grade V, as requested by the Technical Scientific Committee, concerned by the high
 incidence of associated renal dysplasia;

 -  recurrence of acute pyelonephritis before the first dimercaptosuccinic acid (DMSA)
 renal scan, if this was positive for scars.