Evaluation of the Effectiveness of Antibiotic Prophylaxis in Children With a Previous Urinary Tract Infection

NCT ID: NCT00156546

Last Updated: 2005-12-01

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE4

Total Enrollment

660 participants

Study Classification

INTERVENTIONAL

Study Start Date

2000-05-31

Study Completion Date

2006-07-31

Brief Summary

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Our hypothesis is that long-term antimicrobial prophylaxis does not reduce the recurrence of infection and the risk of appearance of kidney scars in children with a documented previous upper UTI.

Detailed Description

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Background

Upper urinary tract infections (UTI) are common in children, especially when functional and anatomical abnormalities of the urinary tract co-exist, such as vesico-ureteral reflux (VUR), urinary tract obstruction uropathy and bladder dysfunction. They are associated with the risk of long-term complications, including permanent renal damage (renal scarring), which occurs in 15% of cases. The objective of the diagnosis and medical treatment of UTI in children is the prevention of such complications. Medical treatment includes long-term antimicrobial prophylaxis to be continued for periods ranging from 6 months to 2 years. Recent studies have revealed the emergence of therapy-induced resistance. A review of the literature has highlighted the lack of properly designed, large clinical trials, demonstrating the efficacy of long-term low-dose antimicrobial prophylaxis in terms of reduction in UTI recurrence.

Methods and design

The study is a controlled, randomised, open-label, 3-armed, parallel-group clinical trial comparing no prophylaxis (group 1) with prophylaxis with co-trimoxazole 15 mg/kg daily (group 2) and with amoxicillin + clavulanic acid 15 mg/kg daily (group 3) for 12 months.

Assuming that the incidence of recurrences is 20%, defining efficacy as an incidence of 10% per group and setting  error = 0.05 and power = 90%, 220 patients per group (i.e. a total of 660 patients) are required The study population will consist of children aged between 2 months and 6 years, with normal renal function (creatinine clearance  70 ml/min/1.73m2) and a first episode of documented UTI, who presents at least one of the following: an acute pyelonephritic lesion at the DMSA scan and/or a VUR at the baseline micturating cystography.

Patients will be followed-up for 12 months. Urinalysis and urine cultures will be performed every month and clinical examinations after 6 and 12 months; both will be performed whenever UTI is suspected. Sonography, Doppler sonography (optional) and DMSA scintigraphy will be performed at baseline and at the end of the study.

Conditions

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Urinary Tract Infections

Keywords

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Urinary tract infections Children Antibiotic prophylaxis Renal scintigraphy Vesico ureteral reflux

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Interventions

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antibiotic to reduce the recurrence of infection

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Age between 2 months and 6 years
* Creatinine clearance (calculated according to Schwartz)  70 ml/min/1.73 m2 (for children in their first year of life, serum creatinine levels within normal range for age and sex)
* First documented upper UTI (diagnostic criteria in Table 1)
* Imaging Diagnostic work-up completed (Table 2) with at least the presence of an acute lesion at the DMSA scan and or a primary non severe reflux ( 1st or 3rd degree)
* Informed consent of parents

Exclusion Criteria

* Patients with chronic renal insufficiency or  30% relative function of one kidney at DMSA scan
* Patients with urinary tract disorders, such as vesico-ureteral reflux due to complex malformations of the urinary tract, obstruction of the posterior urethra, ureterocele or single kidney, neurogenic bladder
* Patients with reflux  4th degree
* Patients with pyelonephritis that developed during prophylaxis instituted because of prenatal diagnosis of urinary tract dilatation  Hypersensitivity to one of the two selected antimicrobial agents
Minimum Eligible Age

2 Months

Maximum Eligible Age

6 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Regione Veneto

OTHER

Sponsor Role collaborator

IL Sogno di Stefano

OTHER

Sponsor Role collaborator

University of Padova

OTHER

Sponsor Role lead

Principal Investigators

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Graziella Zacchello, Professor

Role: STUDY_CHAIR

Departement of Pediatrics, University of Padova

Antonella Toffolo, Dr

Role: PRINCIPAL_INVESTIGATOR

Pediatric Unit Ospedale di Oderzo (TV) Italy

Alessandro Calderan, Dr

Role: PRINCIPAL_INVESTIGATOR

Giovanni Montini, Dr

Role: PRINCIPAL_INVESTIGATOR

Nephrology, Dialysis and Transplant Unit, Pediatric Departement, Azienda Ospedaliera-Università, Padova

Locations

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Pediatric Unit, Ospedale di Belluno

Belluno, Belluno, Italy

Site Status

Pediatric Unit, Ospedale di Bentivoglio

Bentivoglio, Bologna, Italy

Site Status

- Pediatric Department, Ospedale di Bolzano

Bolzano, Bolzano, Italy

Site Status

Pediatric Unit, Ospedale di Cuneo

Cuneo, Cuneo, Italy

Site Status

Pediatric Unit, Ospedale di Este - Monselice

Monselice, Padova, Italy

Site Status

Nephrology, Dialysis and transplant Unit Pediatric Depatment,

Padua, Padova, Italy

Site Status

Pediatric Unit, Ospedale di Piove di Sacco e Chioggia

Piove di Sacco, Padova, Italy

Site Status

Pediatric Unit, Ospedale di Ravenna

Ravenna, Ravenna, Italy

Site Status

Pediatric Unit, Ospedale di Castelfranco

Castelfranco Veneto, Treviso, Italy

Site Status

Pediatric Unit, Ospedale di Motta di Livenza

Motta Di Livenza Oderzo, Treviso, Italy

Site Status

Pediatric Unit, Ospedale di Dolo

Dolo, Venezia, Italy

Site Status

Pediatric Unit, Ospedale di Soave

Soave, Verona, Italy

Site Status

Pediatric Unit, Ospedale di Schio/Thiene

Thiene, Vicenza, Italy

Site Status

Pediatric Department, Ospedale Maggiore

Bologna, , Italy

Site Status

Pediatric Unit, Ospedale di Mestre

Mestre Venezia, , Italy

Site Status

Pediatric Unit, Ospedale di Verona

Verona, , Italy

Site Status

Countries

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Italy

References

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Chon CH, Lai FC, Shortliffe LM. Pediatric urinary tract infections. Pediatr Clin North Am. 2001 Dec;48(6):1441-59. doi: 10.1016/s0031-3955(05)70385-0.

Reference Type BACKGROUND
PMID: 11732124 (View on PubMed)

Benfield MR, McDonald R, Sullivan EK, Stablein DM, Tejani A. The 1997 Annual Renal Transplantation in Children Report of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS). Pediatr Transplant. 1999 May;3(2):152-67. doi: 10.1034/j.1399-3046.1999.00011.x.

Reference Type BACKGROUND
PMID: 10389139 (View on PubMed)

Wennerstrom M, Hansson S, Jodal U, Stokland E. Primary and acquired renal scarring in boys and girls with urinary tract infection. J Pediatr. 2000 Jan;136(1):30-4. doi: 10.1016/s0022-3476(00)90045-3.

Reference Type BACKGROUND
PMID: 10636970 (View on PubMed)

Hoberman A, Wald ER, Hickey RW, Baskin M, Charron M, Majd M, Kearney DH, Reynolds EA, Ruley J, Janosky JE. Oral versus initial intravenous therapy for urinary tract infections in young febrile children. Pediatrics. 1999 Jul;104(1 Pt 1):79-86. doi: 10.1542/peds.104.1.79.

Reference Type BACKGROUND
PMID: 10390264 (View on PubMed)

Downs SM. Technical report: urinary tract infections in febrile infants and young children. The Urinary Tract Subcommittee of the American Academy of Pediatrics Committee on Quality Improvement. Pediatrics. 1999 Apr;103(4):e54. doi: 10.1542/peds.103.4.e54.

Reference Type BACKGROUND
PMID: 10103346 (View on PubMed)

Hohenfellner K, Hunley TE, Brezinska R, Brodhag P, Shyr Y, Brenner W, Habermehl P, Kon V. ACE I/D gene polymorphism predicts renal damage in congenital uropathies. Pediatr Nephrol. 1999 Aug;13(6):514-8. doi: 10.1007/s004670050649.

Reference Type BACKGROUND
PMID: 10452281 (View on PubMed)

Bollgren I. Antibacterial prophylaxis in children with urinary tract infection. Acta Paediatr Suppl. 1999 Nov;88(431):48-52. doi: 10.1111/j.1651-2227.1999.tb01318.x.

Reference Type BACKGROUND
PMID: 10588271 (View on PubMed)

Williams G, Lee A, Craig J. Antibiotics for the prevention of urinary tract infection in children: A systematic review of randomized controlled trials. J Pediatr. 2001 Jun;138(6):868-74. doi: 10.1067/mpd.2001.113785.

Reference Type BACKGROUND
PMID: 11391331 (View on PubMed)

Williams GJ, Lee A, Craig JC. Long-term antibiotics for preventing recurrent urinary tract infection in children. Cochrane Database Syst Rev. 2001;(4):CD001534. doi: 10.1002/14651858.CD001534.

Reference Type BACKGROUND
PMID: 11687116 (View on PubMed)

Ghiro L, Cracco AT, Sartor M, Comacchio S, Zacchello G, Dall'Amico R; Veneto Urinary Tract Infection Study Group. Retrospective study of children with acute pyelonephritis. Evaluation of bacterial etiology, antimicrobial susceptibility, drug management and imaging studies. Nephron. 2002 Jan;90(1):8-15. doi: 10.1159/000046308.

Reference Type BACKGROUND
PMID: 11744799 (View on PubMed)

Montini G, Rigon L, Zucchetta P, Fregonese F, Toffolo A, Gobber D, Cecchin D, Pavanello L, Molinari PP, Maschio F, Zanchetta S, Cassar W, Casadio L, Crivellaro C, Fortunati P, Corsini A, Calderan A, Comacchio S, Tommasi L, Hewitt IK, Da Dalt L, Zacchello G, Dall'Amico R; IRIS Group. Prophylaxis after first febrile urinary tract infection in children? A multicenter, randomized, controlled, noninferiority trial. Pediatrics. 2008 Nov;122(5):1064-71. doi: 10.1542/peds.2007-3770.

Reference Type DERIVED
PMID: 18977988 (View on PubMed)

Hewitt IK, Zucchetta P, Rigon L, Maschio F, Molinari PP, Tomasi L, Toffolo A, Pavanello L, Crivellaro C, Bellato S, Montini G. Early treatment of acute pyelonephritis in children fails to reduce renal scarring: data from the Italian Renal Infection Study Trials. Pediatrics. 2008 Sep;122(3):486-90. doi: 10.1542/peds.2007-2894.

Reference Type DERIVED
PMID: 18762516 (View on PubMed)

Other Identifiers

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IRIS 2

Identifier Type: -

Identifier Source: org_study_id