Symptomatic Therapy of Uncomplicated Lower Urinary Tract Infections in the Ambulatory Setting.

Study Overview
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Brief Summary
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We propose to perform a randomized controlled patient and assessor blind trial in women between the ages of 18 to 70 years with acute uncomplicated UTI to evaluate initial symptomatic treatment for 3 days with the non-steroidal anti-inflammatory drug diclofenac (experimental intervention) against immediate antibiotic treatment with norfloxacin for 3 days (control intervention). Both interventions are followed by optional delayed antibiotic treatment with single dose fosfomycin if deemed necessary by the patients. The primary objective is to determine whether initial symptomatic treatment followed by optional delayed antibiotic treatment (experimental intervention) is non-inferior to immediate antibiotic treatment (control intervention) in terms of symptom resolution.

Detailed Description
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Background Urinary tract infection (UTI) is the most frequent bacterial infection diagnosed and treated by general practitioners and accounts for about 15% of antibiotic prescriptions in ambulatory medicine. World-wide raise of antibiotic resistance among uropathogens, most commonly Escherichia coli, threatens treatment of UTI. Uncomplicated UTI, the most frequent manifestation of UTI, is a benign, self-limited disease and the primary goal of treatment is symptom relief not cure. Antibiotic treatment reduces the duration of symptoms by 1-2 days from 5-6 days to 3-4 days. Symptoms of cystitis are the result of an inflammation evoked by bacterial products which stimulate the production of prostaglandins by a cyclooxygenase dependent mechanism. Therefore, we propose that symptom control with a non-steroidal anti-inflammatory drug (NSAID), an inhibitor of cyclooxygenase 1 and 2, may be equally effective for symptom control as standard antibiotic therapy in non-complicated UTI and may therefore help to reduce antibiotic consumption. Objective The primary objective is to determine whether initial symptomatic treatment followed by optional delayed antibiotic treatment (experimental intervention) is non-inferior to immediate antibiotic treatment followed by optional delayed antibiotic treatment (control intervention) in terms of symptom resolution. The secondary objective is to determine whether the experimental intervention is superior to control in reducing the proportion of patients undergoing antibiotic treatment. Methods Randomized controlled patient and assessor blind trial performed in general practices. Study population are women between the ages of 18 to 70 years with acute uncomplicated UTI. The experimental intervention will consist of symptomatic treatment with diclofenac 75mg twice daily, followed by optional, delayed antibiotic treatment with single dose of 3g fosfomycin if deemed necessary by the patient. The control intervention will consist of immediate antibiotic treatment with norfloxacin 400mg twice daily for three days, followed by optional, delayed antibiotic treatment with single dose of 3g fosfomycin if deemed necessary by the patient. Patients will use a diary to describe symptoms for 10 days. A follow-up telephone interview will be performed on day 10 and 30.

Official Title
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Symptomatic Therapy of Uncomplicated Lower Urinary Tract Infections in the Ambulatory Setting. A Randomized, Double Blind Trial

Conditions
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Urinary Tract Infections

Intervention / Treatment
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* Drug: Diclofenac
* Drug: Norfloxacin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female Age between 18 and 70 years Written informed consent At least one typical symptom of acute, lower urinary tract infection out of dysuria, frequency, macrohaematuria, cloudy or smelly urine or self-diagnosed cystitis A urine dipstick test should be indicative of UTI by positive nitrite or leucocyturia Exclusion Criteria Duration of UTI symptoms for more than 7 days before physician's visit Clinical signs of invasiveness such as fever (axillary body temperature >38 degrees Celsius), costovertebral pain or tenderness, rigors, nausea or vomiting Known or suspicion of anatomical or functional abnormality of the urinary tract Vaginal symptoms: discharge, irritation Diabetes mellitus Immunosuppression (e.g. prednisone equivalent >10mg per day for >14 days, chemotherapy, radiotherapy, immunomodulators, HIV infection, neutropenia) Any other serious comorbidity as judged by the treating physician Bladder catheter in situ or during the past 30 days Pregnancy Recurrent urinary tract infection (more than 3 infections during the last 12 months) Antibiotic treatment during the last 4 weeks Hypersensitivity to one of the study medications Psychiatric illness or dementia Unable to communicate in German or French language Documented coagulopathy (including therapy with coumarine derivatives) or documented history of gastric or duodenal ulcer disease Documented renal insufficiency grade III or higher (calculated GFR <60) or known congestive heart failure (NYHA III or higher)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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Female

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: antibiotic<br>Norfloxacin for three days, followed by fosfomycin on day 4 if deemed necessary | Drug: Norfloxacin<br>* Norfloxacin 400mg twice daily for 3 days, followed by fosfomycin 3g single dose on day 4 if deemed necessary<br>|
| Experimental: symptomatic<br>Diclofenac retard for three days, followed by fosfomycin on day 4 if deemed necessary | Drug: Diclofenac<br>* Diclofenac retard 75mg twice daily for 3 days, followed by fosfomycin 3g single dose on day 4 if deemed necessary<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of patients with resolution of symptoms on day 4 |  | one month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of patients ever on antibiotics between randomization at day 1 and follow-up at day 30 |  | one month | 
| The proportion of patients using single dose fosfomycin on day 4 |  | one month | 
| The proportion of patients with re-consultations because of UTI within 30 days |  | one month | 
| The mean composite symptom scores on days 4, 7 and 30 |  | one month | 
| The proportion of patients with resolution of symptoms on day 7 |  | one month | 
| The proportion of patients with complete resolution of symptoms on days 4 and 7 |  | one month | 
| The time until resolution of symptoms |  | one month | 
| The proportion of patients with adverse events |  | one month | 
| Mean overall patient stratification |  | one month | 
| Health-related quality of life on day 4 |  | one month | 
| Number of working days lost |  | one month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Urinary tract infections, Anti-bacterial agents