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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Ronfani Luca, IRCCS Burlo Garofolo
ClinicalTrials.gov Identifier:
NCT00382343
First received: September 28, 2006
Last updated: April 27, 2015
Last verified: April 2015
  Purpose
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 Intervention Phase
Pyelonephritis
Renal Scars
Drug: Sulfamethoxazole/trimethoprim
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Antibiotic Prophylaxis After Acute Pyelonephritis for Prevention of Urinary Tract Infections in Children With Vesico-Ureteral Reflux.

Resource links provided by NLM:


Further study details as provided by IRCCS Burlo Garofolo:

Primary Outcome Measures:
  • Recurrence of pyelonephritis [ Time Frame: up to 4 years after enrollment ] [ Designated as safety issue: No ]
    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:
  • Renal scars [ Time Frame: 4 years after enrollment ] [ Designated as safety issue: No ]
    DMSA renal scan

  • Persistence of vesico-ureteral reflux [ Time Frame: 4 years after enrollment ] [ Designated as safety issue: No ]
    Cystourethrography and renal ultrasound


Enrollment: 96
Study Start Date: November 1999
Study Completion Date: March 2007
Primary Completion Date: March 2003 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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

Ages Eligible for Study:   up to 30 Months   (Child)
Genders Eligible for Study:   Both
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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Please refer to this study by its ClinicalTrials.gov identifier: NCT00382343

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

Publications:
Responsible Party: Ronfani Luca, MD, PhD, IRCCS Burlo Garofolo
ClinicalTrials.gov Identifier: NCT00382343     History of Changes
Other Study ID Numbers: RC 35/00 
Study First Received: September 28, 2006
Last Updated: April 27, 2015
Health Authority: Italy: Ministry of Health

Keywords provided by 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

ClinicalTrials.gov processed this record on September 23, 2016