The main objectives of the study are

1. to compare the efficacy of oral vs initial iv antibiotic treatment in children with a first episode of UTI
2. to assess the diagnostic power of the various imaging technique (renal ultrasonogram, voiding cystourethrogram, and renal scanning with technetium-99m-labeled dimercaptosuccinic acid)

Condition	Intervention	Phase
Urinary Tract Infections	Drug: oral amoxicilline/clavulanic acid  Drug: iv ceftriaxone	Phase III

Further Study Details: 

Primary Outcomes: 1. Duration of fever (>38°),; 2. Sterilization of the urine,; 3. Reduction of the blood inflammatory indices,; 4. Incidence of renal scarring documented at 12 month.
Expected Total Enrollment:  440

Background. Upper urinary tract infections (UTIs) are common in children, but attitudes toward the diagnosis and the acute treatment are heterogeneous among pediatricians and pediatric nephrologists. In effect the choice of antibiotic regimens is largely empirical and based on local practice, with no rationale for the choice of oral or parenteral administration. A retrospective study (1993-97) showed that in 1333 (36 % M) hospitalized children because of a prove UTI, parenteral antibiotic was given initially to 756 (57.2%) of the population studied.

We are aware of a unique randomized clinical trial, which has shown no differences in the short term (mean time to defervescence) and long term outcomes (symptomatic reinfections and renal scarring) of children receiving oral cefixime for 14 days versus vs initial iv cefotaxime for 3 days, followed by oral cefixime for 11 days.

The management of patients with UTI consists not only in antibiotic treatment of acute episodes, but also in the global evaluation of any risk factors. Current recommendations for imaging of the urinary tract are not based on prospective studies of outcomes (development of renal scars). A recent publication (Hoberman et al) suggests that renal ultrasonography and DMSA scanning at the time of acute illness are of limited value and recommends the routine use of voiding cystourethrography to identify children with reflux.

Aims.

Main objective of the study is:

1. to compare the efficacy of oral vs initial iv antibiotic treatment in children with a first episode of UTI;

Secondary objectives of the study are:

1. to assess the diagnostic power of the various imaging technique (renal ultrasonogram, voiding cystourethrogram, and renal scanning with technetium-99m-labeled dimercaptosuccinic acid);
2. to evaluate a possible role of genetic polymorphisms implicated in the evolution of kidney damage
3. to obtain area based protocols for the treatment and hospitalization of children with UTI.

Study design. A randomised, controlled, open-label, 2-armed, parallel-group study comparing the safety and efficacy of oral antibiotic (10 days of amoxicillin + clavulanic acid 50 mg/Kg/day), vs initial iv treatment (ceftriaxon 50 mg/Kg/day until defervescence) followed by oral treatment (amoxicillin + clavulanic acid) for a total of 10 days, in children with a first episode of UTI.

Criteria for the diagnosis of upper UTI upon entry

1. Urinalysis (two concordant consecutive tests)  Urine WBC ( higher 25/ul = 1+ with dipstick)
2. Urine culture (two concordant consecutive tests)  Growth of only one microorganism  100,000 CFU
3. Fever higher than 38°C (NB: in the first 6 months of life fever is not an essential criterion)
4. Inflammation indices in the first 48 hours ESR higher than 30 and/or C-reactive Protein more than 3 times the upper limit of normal values
5. Neutrophils higher than the normal values for age

The diagnosis of upper UTI is made by presence of criteria 1, 2 and at least two of the others.

Assuming that 15% of children with pyelonephritis and treated iv will develop renal scars at the 12 month DMSA, defining efficacy as an incidence of 10% per group and setting alfa error = 0.05 and power = 80%, 220 patients per group (i.e. a total of 440 patients) are required.

The computer generated randomization list is stratified for hospital, sex and age (< o > than 2 years) and based on variable blocks of 10 or more.

Primary end points are:1. Duration of fever (>38°), 2. Sterilization of the urine, 3. Reduction of the blood inflammatory indices, 4. Incidence of renal scarring documented at 12 month.

The imaging diagnostic work-up is as follow: sonography (US) of the kidney and the bladder and DMSA renal scintigraphy within 10 days from onset of antibiotic treatment and at the end of the study (12 months), voiding cystourethrography (VC) 1-2 months after UTI.

Ages Eligible for Study:  2 Months   -   6 Years,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria:

• age between 2 months and 6 years,
• normal renal function
• first episode of upper UTI (fever, 2 consecutive positive urinalysis, later confirmed by 2 cultures and high blood inflammation indices)

Exclusion Criteria:

• documented previous urinary tract malformation (prenatal ultrasound)
• seriously compromised general conditions (such as sepsis or vomit)
• hypersensitivity to the antibiotics considered.

Study chairs or principal investigators

Graziella Zacchello, Professor,  Study Chair,  Nephrology, dialysis and transplant unit, Pediatric Departement, Azienda ospdealiera-università, Padova   
Antonella Toffolo, Dr,  Principal Investigator,  Pediatric Unit, Ospedale di Oderzo, Italy   
Giovanni Montini, Dr,  Principal Investigator,  Nephrology, Dialysis and Transplant Unit, Pediatric Departement, Azienda Ospedaliera - Università, Padova Italy   

Study ID Numbers:  IRIS 1
Last Updated:  September 11, 2005
Record first received:  September 8, 2005
ClinicalTrials.gov Identifier:  NCT00161330
Health Authority: Italy: National Monitoring Centre for Clinical Trials - Ministry of Health
ClinicalTrials.gov processed this record on 2005-09-13