Antibiotic to reduce the recurrence of infection in Urinary Tract Infections - Clinical Trials Registry

Study Overview

Status

Unknown

Conditions

Urinary Tract Infections

Intervention / Treatment

Drug: antibiotic to reduce the recurrence of infection

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.

Study Type

Interventional

Enrollment

660

Phase

Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Italy
- - Belluno, Italy
    - Pediatric Unit, Ospedale di Belluno
  - Bologna, Italy
    - Pediatric Department, Ospedale Maggiore
  - Bolzano, Italy
    - - Pediatric Department, Ospedale di Bolzano
  - Cuneo, Italy
    - Pediatric Unit, Ospedale di Cuneo
  - Mestre Venezia, Italy
    - Pediatric Unit, Ospedale di Mestre
  - Padova, Italy, 35128
    - Nephrology, Dialysis and transplant Unit Pediatric Depatment,
  - Ravenna, Italy
    - Pediatric Unit, Ospedale di Ravenna
  - Verona, Italy
    - Pediatric Unit, Ospedale di Verona
- Bologna
  - Bentivoglio, Bologna, Italy
    - Pediatric Unit, Ospedale di Bentivoglio
- Padova
  - Monselice, Padova, Italy
    - Pediatric Unit, Ospedale di Este - Monselice
  - Piove di Sacco, Padova, Italy
    - Pediatric Unit, Ospedale di Piove di Sacco e Chioggia
- Treviso
  - Castelfranco Veneto, Treviso, Italy
    - Pediatric Unit, Ospedale di Castelfranco
  - Motta di Livenza Oderzo, Treviso, Italy
    - Pediatric Unit, Ospedale di Motta di Livenza
- Venezia
  - Dolo, Venezia, Italy
    - Pediatric Unit, Ospedale di Dolo
- Verona
  - Soave, Verona, Italy
    - Pediatric Unit, Ospedale di Soave
- Vicenza
  - Thiene, Vicenza, Italy
    - Pediatric Unit, Ospedale di Schio/Thiene

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

2 months to 6 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
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
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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Padova

Collaborators

IL Sogno di Stefano

Regione Veneto

Investigators

Study Chair: Graziella Zacchello, Professor, Departement of Pediatrics, University of Padova
Principal Investigator: Antonella Toffolo, Dr, Pediatric Unit Ospedale di Oderzo (TV) Italy
Principal Investigator: Alessandro Calderan, Dr
Principal Investigator: Giovanni Montini, Dr, Nephrology, Dialysis and Transplant Unit, Pediatric Departement, Azienda Ospedaliera-Università, Padova

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2000

Study Completion

July 1, 2006

Study Registration Dates

First Submitted

September 7, 2005

First Submitted That Met QC Criteria