Symptomatic Therapy of Uncomplicated Lower Urinary Tract Infections in the Ambulatory Setting. - Full Text View

Sponsor:	University Hospital Inselspital, Berne
Collaborators:	Institute for Infectious Diseases, University of Berne, Switzerland CTU Bern, Bern University Hospital, and Institute of Social and Preventive Medicine, University of Bern, Switzerland Clinic for Infectious Diseases, University Hospital Bern, Switzerland University of Bern
Information provided by:	University Hospital Inselspital, Berne
ClinicalTrials.gov Identifier:	NCT01039545

Purpose

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	Intervention	Phase
Urinary Tract Infections	Drug: Diclofenac Drug: Norfloxacin	Phase 4

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Pharmacodynamics Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:

MedlinePlus related topics: Antibiotics Urinary Tract Infections

Drug Information available for: Diclofenac sodium Diclofenac potassium Diclofenac Norfloxacin

U.S. FDA Resources

Further study details as provided by University Hospital Inselspital, Berne:

Primary Outcome Measures:

The proportion of patients with resolution of symptoms on day 4 [ Time Frame: one year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

The proportion of patients ever on antibiotics between randomization and day 30 of follow-up [ Time Frame: one year ] [ Designated as safety issue: No ]
The proportion of patients using single dose fosfomycin on day 4 [ Time Frame: one year ] [ Designated as safety issue: No ]
The proportion of patients with re-consultations because of UTI within 30 days [ Time Frame: one year ] [ Designated as safety issue: No ]
The mean composite symptom scores on days 4, 7 and 30 [ Time Frame: one year ] [ Designated as safety issue: No ]
The proportion of patients with resolution of symptoms on day 7 [ Time Frame: one year ] [ Designated as safety issue: No ]
The proportion of patients with complete resolution of symptoms on days 4 and 7 [ Time Frame: one year ] [ Designated as safety issue: No ]
The time until resolution of symptoms [ Time Frame: one year ] [ Designated as safety issue: Yes ]
The proportion of patients with adverse events [ Time Frame: one year ] [ Designated as safety issue: Yes ]
Mean overall patient stratification [ Time Frame: one year ] [ Designated as safety issue: No ]
Health-related quality of life on day 4 [ Time Frame: one year ] [ Designated as safety issue: No ]
Number of working days lost [ Time Frame: one year ] [ Designated as safety issue: No ]

Estimated Enrollment:	400
Study Start Date:	January 2012
Estimated Study Completion Date:	August 2013
Estimated Primary Completion Date:	February 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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

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.

Eligibility

Ages Eligible for Study:	18 Years to 70 Years
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

female
age between 18 and 70 years
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)

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01039545

Contacts

Contact: Kathrin Mühlemann

+41 (0)31 632 32 59

kathrin.mühlemann@ifik.unibe.ch

Locations

Switzerland
Institute for Infectious Diseases, University of Berne	Not yet recruiting
Berne, Switzerland, 3010
Principal Investigator: Kathrin Mühlemann

Sponsors and Collaborators

University Hospital Inselspital, Berne

Institute for Infectious Diseases, University of Berne, Switzerland

CTU Bern, Bern University Hospital, and Institute of Social and Preventive Medicine, University of Bern, Switzerland

Clinic for Infectious Diseases, University Hospital Bern, Switzerland

University of Bern

Investigators

Principal Investigator:

Kathrin Mühlemann

Institute for Infectious Diseases, University of Berne, Switzerland

More Information

No publications provided

Responsible Party:	Kathrin Mühlemann, Co-Director Institute for Infectious Diseases, University of Berne and Head of infection control and attending physician, Clinic for Infectious Diseases, University Hospital Bern, Switzerland
ClinicalTrials.gov Identifier:	NCT01039545 History of Changes
Other Study ID Numbers:	254/09
Study First Received:	December 24, 2009
Last Updated:	November 10, 2011
Health Authority:	Switzerland: Independent Local Research Ethic Commission (Ethikkommission) Switzerland: Swiss Agency for therapeutic products (Swissmedic)

Keywords provided by University Hospital Inselspital, Berne:

Urinary tract infections
Anti-bacterial agents

Additional relevant MeSH terms:

Urinary Tract Infections
Infection
Urologic Diseases
Diclofenac
Norfloxacin
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs

Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Central Nervous System Agents
Nucleic Acid Synthesis Inhibitors
Anti-Bacterial Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on May 23, 2012