Clinical trial NCT00382343: A Randomized Controlled Trial on Antibiotic Prophylaxis in Children With Vesico-Ureteral Reflux
Official title: Antibiotic Prophylaxis After Acute Pyelonephritis for Prevention of Urinary Tract Infections in Children With Vesico-Ureteral Reflux.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Pyelonephritis
Renal Scars
Keywords: Prevention
Pyelonephritis
Renal scars
Vesico-ureteral reflux
Dimercaptosuccinic acid renal scan (DMSA)
Lead sponsor: IRCCS Burlo Garofolo
Sponsor class: OTHER
First posted: 2006-09-29
Enrollment: 96
Sex: ALL
Minimum age (years): 1
Maximum age (years): 30
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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).

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.

Eligibility 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.

Primary outcomes:
measure: Recurrence of pyelonephritis
timeFrame: up to 4 years after enrollment
Secondary outcomes:
measure: Renal scars
timeFrame: 4 years after enrollment
measure: Persistence of vesico-ureteral reflux
timeFrame: 4 years after enrollment
Other outcomes:
Locations:
city: Monfalcone
country: Italy
facility: San Polo Hospital
state: Gorizia
city: San Daniele
country: Italy
facility: San Daniele Hospital
state: Udine
city: Tolmezzo
country: Italy
facility: Sant'Antonio Abate Hospital
state: Udine
city: Bologna
country: Italy
facility: Sant'Orsola Hospital
city: Cesena
country: Italy
facility: Bufalini Hospital
city: Pordenone
country: Italy
facility: Santa Maria degli Angeli Hospital
city: Trieste
country: Italy
facility: Institute of Child Health IRCCS Burlo Garofolo
Study officials:
affiliation: Institute of Child Health IRCCS Burlo Garofolo, Trieste, Italy
name: Marco Pennesi, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Pennesi M, Travan L, Peratoner L, Bordugo A, Cattaneo A, Ronfani L, Minisini S, Ventura A; North East Italy Prophylaxis in VUR study group. Is antibiotic prophylaxis in children with vesicoureteral reflux effective in preventing pyelonephritis and renal scars? A randomized, controlled trial. Pediatrics. 2008 Jun;121(6):e1489-94. doi: 10.1542/peds.2007-2652. Epub 2008 May 19.