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

Study Description

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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).

Condition or disease	Intervention/treatment	Phase
Pyelonephritis; Renal Scars	Drug: Sulfamethoxazole/trimethoprim	Phase 4

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.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	96 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Prevention
Official Title:	Antibiotic Prophylaxis After Acute Pyelonephritis for Prevention of Urinary Tract Infections in Children With Vesico-Ureteral Reflux.
Study Start Date :	November 1999
Actual Primary Completion Date :	March 2003
Actual Study Completion Date :	March 2007

Arms and Interventions

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Arm	Intervention/treatment
Experimental: sulfamethoxazole/trimethoprim; Antibiotic prophylaxis with sulfamethoxazole/trimethoprim [1-2 mg/kg trimethoprim and 5-10 mg/kg sulfamethoxazole once daily]; in case of intolerance (leucopoenia) and for children younger than 6 months: nitrofurantoin [2 mg/kg once daily]	Drug: Sulfamethoxazole/trimethoprim; Sulfamethoxazole/trimethoprim prophylaxis
No Intervention: No prophylaxis

Outcome Measures

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Primary Outcome Measures :

1. Recurrence of pyelonephritis [ Time Frame: up to 4 years after enrollment ]
   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)

Secondary Outcome Measures :

1. Renal scars [ Time Frame: 4 years after enrollment ]
   DMSA renal scan
2. Persistence of vesico-ureteral reflux [ Time Frame: 4 years after enrollment ]
   Cystourethrography and renal ultrasound

Eligibility Criteria

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Ages Eligible for Study:	up to 30 Months (Child)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

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Locations

Italy
San Polo Hospital
Monfalcone, Gorizia, Italy, 34170
San Daniele Hospital
San Daniele, Udine, Italy, 33100
Sant'Antonio Abate Hospital
Tolmezzo, Udine, Italy, 33028
Sant'Orsola Hospital
Bologna, Italy, 48138
Bufalini Hospital
Cesena, Italy, 47023
Santa Maria degli Angeli Hospital
Pordenone, Italy, 33170
Institute of Child Health IRCCS Burlo Garofolo
Trieste, Italy, 34137

Sponsors and Collaborators

IRCCS Burlo Garofolo

Investigators

Principal Investigator:	Marco Pennesi, MD	Institute of Child Health IRCCS Burlo Garofolo, Trieste, Italy

More Information

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Publications of Results:

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.

Responsible Party:	Ronfani Luca, MD, PhD, IRCCS Burlo Garofolo
ClinicalTrials.gov Identifier:	NCT00382343 History of Changes
Other Study ID Numbers:	RC 35/00
First Posted:	September 29, 2006
Last Update Posted:	April 28, 2015
Last Verified:	April 2015

Keywords provided by Ronfani Luca, IRCCS Burlo Garofolo:

Prevention; Pyelonephritis; Renal scars; Vesico-ureteral reflux; Dimercaptosuccinic acid renal scan (DMSA)

Additional relevant MeSH terms:

Pyelonephritis; Vesico-Ureteral Reflux; Nephritis, Interstitial; Nephritis; Kidney Diseases; Urologic Diseases; Pyelitis; Urinary Bladder Diseases; Anti-Bacterial Agents; Trimethoprim, Sulfamethoxazole Drug Combination; Antibiotics, Antitubercular; Trimethoprim; Sulfamethoxazole	Anti-Infective Agents; Antitubercular Agents; Anti-Infective Agents, Urinary; Renal Agents; Antimalarials; Antiprotozoal Agents; Antiparasitic Agents; Folic Acid Antagonists; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Cytochrome P-450 CYP2C8 Inhibitors; Cytochrome P-450 Enzyme Inhibitors