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

Sponsor

University Hospital Inselspital, Berne (Other)

Overall Status

Terminated

CT.gov ID

NCT01039545

Collaborator

University of Bern (Other), Clinic for Infectious Diseases, University Hospital Bern, Switzerland (Other)

253

Enrollment

Location

Arms

Duration (Months)

7.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Urinary Tract Infections	Drug: Diclofenac Drug: Norfloxacin	Phase 4

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

253 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Feb 1, 2012

Actual Primary Completion Date :

Dec 1, 2014

Actual Study Completion Date :

Jan 1, 2015

Arms and Interventions

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

Arm

Intervention/Treatment

Active Comparator: antibiotic

Norfloxacin for three days, followed by fosfomycin on day 4 if deemed necessary

Drug: Norfloxacin

Norfloxacin 400mg twice daily for 3 days, followed by fosfomycin 3g single dose on day 4 if deemed necessary

Experimental: symptomatic

Diclofenac retard for three days, followed by fosfomycin on day 4 if deemed necessary

Drug: Diclofenac

Diclofenac retard 75mg twice daily for 3 days, followed by fosfomycin 3g single dose on day 4 if deemed necessary

Outcome Measures

Primary Outcome Measures

The proportion of patients with resolution of symptoms on day 4 [one month]

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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)