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

Pyelonephritis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00382343
• Other study ID #: RC 35/00
• Status: Completed
• Phase: Phase 4
• First received: September 28, 2006
• Last updated: April 27, 2015
• Start date: November 1999
• Est. completion date: March 2007

Study information

• Verified date: April 2015
• Source: IRCCS Burlo Garofolo
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: Ministry of Health
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 96
• Est. completion date: March 2007
• Est. primary completion date: March 2003
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 30 Months

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Pyelonephritis
• Renal Scars
• Vesico-Ureteral Reflux

Intervention

Drug:
• Sulfamethoxazole/trimethoprim
Sulfamethoxazole/trimethoprim prophylaxis

Locations

Country	Name	City	State
Italy	Sant'Orsola Hospital	Bologna
Italy	Bufalini Hospital	Cesena
Italy	San Polo Hospital	Monfalcone	Gorizia
Italy	Santa Maria degli Angeli Hospital	Pordenone
Italy	San Daniele Hospital	San Daniele	Udine
Italy	Sant'Antonio Abate Hospital	Tolmezzo	Udine
Italy	Institute of Child Health IRCCS Burlo Garofolo	Trieste

Sponsors (1)

Lead Sponsor	Collaborator
IRCCS Burlo Garofolo

Country where clinical trial is conducted

Italy, 

References & Publications (1)

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 s — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Recurrence of pyelonephritis	Urinalysis and urine culture performed at each episode of fever or when symptoms of UTI occurred (eg, change in the smell of urine, anorexia, irritability)	up to 4 years after enrollment	No
Secondary	Renal scars	DMSA renal scan	4 years after enrollment	No
Secondary	Persistence of vesico-ureteral reflux	Cystourethrography and renal ultrasound	4 years after enrollment	No