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

Urinary Tract Infections Clinical Trial

Official title:

Evaluation of the Effectiveness of Antibiotic Prophylaxis in Children With a History of Upper Urinary Tract Infections:a Multicentre Randomised Study

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00156546
• Other study ID #: IRIS 2
• Status: Active, not recruiting
• Phase: Phase 4
• First received: September 7, 2005
• Last updated: November 30, 2005
• Start date: May 2000
• Est. completion date: July 2006

Study information

• Verified date: September 2005
• Source: University of Padova
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: National Monitoring Centre for Clinical Trials - Ministry of Health
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 660
• Est. completion date: July 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 2 Months to 6 Years

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Communicable Diseases
• Infection
• Urinary Tract Infections

Intervention

Drug:
• antibiotic to reduce the recurrence of infection

Locations

Country	Name	City	State
Italy	Pediatric Unit, Ospedale di Belluno	Belluno
Italy	Pediatric Unit, Ospedale di Bentivoglio	Bentivoglio	Bologna
Italy	Pediatric Department, Ospedale Maggiore	Bologna
Italy	- Pediatric Department, Ospedale di Bolzano	Bolzano
Italy	Pediatric Unit, Ospedale di Castelfranco	Castelfranco Veneto	Treviso
Italy	Pediatric Unit, Ospedale di Cuneo	Cuneo
Italy	Pediatric Unit, Ospedale di Dolo	Dolo	Venezia
Italy	Pediatric Unit, Ospedale di Mestre	Mestre Venezia
Italy	Pediatric Unit, Ospedale di Este - Monselice	Monselice	Padova
Italy	Pediatric Unit, Ospedale di Motta di Livenza	Motta di Livenza Oderzo	Treviso
Italy	Nephrology, Dialysis and transplant Unit Pediatric Depatment,	Padova
Italy	Pediatric Unit, Ospedale di Piove di Sacco e Chioggia	Piove di Sacco	Padova
Italy	Pediatric Unit, Ospedale di Ravenna	Ravenna
Italy	Pediatric Unit, Ospedale di Soave	Soave	Verona
Italy	Pediatric Unit, Ospedale di Schio/Thiene	Thiene	Vicenza
Italy	Pediatric Unit, Ospedale di Verona	Verona

Sponsors (3)

Lead Sponsor	Collaborator
University of Padova	IL Sogno di Stefano, Regione Veneto

Country where clinical trial is conducted

Italy, 

References & Publications (10)

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. — View Citation

Bollgren I. Antibacterial prophylaxis in children with urinary tract infection. Acta Paediatr Suppl. 1999 Nov;88(431):48-52. Review. — View Citation

Chon CH, Lai FC, Shortliffe LM. Pediatric urinary tract infections. Pediatr Clin North Am. 2001 Dec;48(6):1441-59. Review. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Wennerström 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. — View Citation

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. Review. — View Citation

Williams GJ, Lee A, Craig JC. Long-term antibiotics for preventing recurrent urinary tract infection in children. Cochrane Database Syst Rev. 2001;(4):CD001534. Review. Update in: Cochrane Database Syst Rev. 2006;(3):CD001534. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The primary end-point is UTI Recurrence Rate during the 12-month observation period and the Development of renal damage (parenchymal scar) after 12 months.
Secondary	The secondary objectives are the comparison, in terms of efficacy and effectiveness, between two antimicrobial agents that are currently approved for prophylactic use: co-trimoxazole 15 mg/kg daily versus amoxicillin + clavulanic acid 15 mg/kg daily.