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

Study Overview
=================
Brief 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.

Detailed 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.

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

Conditions
-----------------
Urinary Tract Infections

Intervention / Treatment
-----------------
* Drug: antibiotic to reduce the recurrence of infection


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 2 Months
Maximum Age: 6 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: antibiotic to reduce the recurrence of infection|nan|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. |  |  | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Urinary tract infections, Children, Antibiotic prophylaxis, Renal scintigraphy, Vesico ureteral reflux