A Randomized Controlled Trial on Antibiotic Prophylaxis in Children With Vesico-Ureteral Reflux

Condition(s) targeted: Pyelonephritis; Renal Scars

Intervention: sulfamethoxazole/trimethoprim or nitrofurantoin prophylaxis (Drug)

Phase: Phase 4

Status: Completed

Sponsored by: IRCCS Burlo Garofolo

Official(s) and/or principal investigator(s):
Marco Pennesi, MD, Principal Investigator, Affiliation: Institute of Child Health IRCCS Burlo Garofolo, Trieste, Italy

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).

Official title: Antibiotic Prophylaxis After Acute Pyelonephritis for Prevention of Urinary Tract Infections in Children With Vesico-Ureteral Reflux.

Study design: Prevention, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study

Primary outcome:

Recurrence of pyelonephritis

Renal scars

Secondary outcome: Persistence of vesico-ureteral reflux

Detailed description: 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.

Minimum age: N/A. Maximum age: 30 Months. Gender(s): Both.

Criteria:

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.

Sant'Orsola Hospital, Bologna 48138, Italy

Bufalini Hospital, Cesena 47023, Italy

Santa Maria degli Angeli Hospital, Pordenone 33170, Italy

Institute of Child Health IRCCS Burlo Garofolo, Trieste 34137, Italy

San Polo Hospital, Monfalcone, Gorizia 34170, Italy

Sant'Antonio Abate Hospital, Tolmezzo, Udine 33028, Italy

San Daniele Hospital, San Daniele, Udine 33100, Italy

Starting date: November 1999
Ending date: May 2006
Last updated: September 28, 2006