Preventing Urinary Tract Infections With E. Coli Nissle:

Study Overview
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Brief Summary
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Urinary tract infections (UTIs) account for 5-14% of pediatric emergency department visits annually. At the moment, up to one third of children suffering of acute (UTI) will have a new infection and there is a lack of effective methods for preventing secondary UTIs in young children. Majority of UTIs in children are caused by intestinal bacteria of the patient, mainly E. coli that colonizes gut of the patient. E. coli Nissle is a probiotic strain that has been used successfully for treating acute gastrointestinal infections in children. The strain has also been proved to be safe for infants and young children. E. coli Nissle could be a potential solution for preventing recurrent urinary tract infections in children as it competes with pathogenic bacteria that usually cause UTIs in children. The aim of this study is to evaluate efficacy of E. coli Nissle strain in secondary prevention of urinary tract infections in young children.

Detailed Description
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In order to asses efficacy of E. coli Nissle strain in prevention of recurrent UTIs in children, we aim to conduct randomized, placebo controlled and double blinded clinical trial. We are going to recruit children who are suffering the first urinary tract infection of their life. The UTI will be treated by normal clinical recommendations decided by treating physician. Intervention will start on the day following the last day of the antimicrobial course. The intervention will last for 15 days and the study participants will receive either intervention drug or placebo. Intervention drug contains 10 E8 CFU/ml of E. coli Nissle strain and will be administered as dose of 1 ml of oral suspension once daily for children aged under one year and twice daily for children aged more than one year. The study patients will be monitored by monthly electronic surveys for six months after the intervention in order to measure proportion of the children who will have a new UTI during the follow up. We are also going to record possible adverse effects in both study groups. Also use of antimicrobial medication due to any reason will be recorded.

Official Title
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Preventing Urinary Tract Infections in Infants and Young Children With Probiotic E. Coli Nissle:

Conditions
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Urinary Tract Infections in Children, Secondary Prevention

Intervention / Treatment
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* Drug: E. coli Nissle
* Other: Placebo control


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Children who suffer of the first urinary tract infection of their life defined as pyuria, presence of symptoms (fever or focal symptom), no other explanation for infection, bacterial culture positive or culture result pending Written informed consent Exclusion Criteria: Preterm birth, gestational age less than 35 weeks Signs of life-threatening infection (such as meningitis) Detected anomaly in urinary tract Primary immunodeficiency Detected anomaly of GE tract Ongoing antimicrobial prophylaxis Hospital-acquired infection

Ages Eligible for Study
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Maximum Age: 2 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Double Blinded, Placebo controlled and randomized clinical trial
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nissle group<br>Intervention will start on the day following the ending of the antimicrobial treatment of the UTI. Patients will receive 1 ml of oral suspension containing 10 E8 CFU/ml of E coli Nissle. Patients under one year of age will receive one daily dose and patients aged more than one year will receive a dose twice daily. Intervention will last for 30 days | Drug: E. coli Nissle<br>* 1 ml of oral suspension containing 10 E8 CFU /ml of E. coli Nissle strain<br>* Other names: Mutaflor;|
| Placebo Comparator: Control group<br>Intervention will start on the day following the ending of the antimicrobial treatment of the UTI. Patients will receive 1 ml of oral syrup consisting of Saccharum 630 mg/g and Aqua purificata 370 mg/g. Patients under one year of age will receive one daily dose and patients aged more than one year will receive a dose twice daily. Intervention will last for 30 days | Other: Placebo control<br>* 1 ml oral syrup consisting of Saccharum 630 mg/g and Aqua purificata 370 mg/g.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recurrence of urinary tract infections | Proportion of the study patient who will have at least one bacterial culture confirmed urinary tract infection | Six months from study entry | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of urinary tract infections | Number of bacterial culture confirmed urinary tract infections per person years at risk (PYR) | Six months from study entry | 
| Hospitalization day due to bacterial culture confirmed urinary tract infection | Number of days spent in the hospital during follow up | Six months from study entry | 
| Antimicrobial treatment days for suspected or confirmed urinary tract infection | Number of days when study patient has received antimicrobial treatment | Six months, starting after the initial treatment at study entry has ended | 
| Stomach pain | Number of days with stomach pain reported by families during follow up at web-based surveys | Six months from study entry | 
| Diarrhea | Number of days with diarrhea reported by families during follow up at web-based survey | Six months from study entry | 
| Antimicrobial treatment days for any indication | Number of days when study patient has received antimicrobial treatment | Six months, starting after the initial treatment at study entry has ended | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Urinary Tract Infections, E. coli