Urinary Tract InfectionsPhase 4NCT01039545
Symptomatic Therapy of Uncomplicated Lower Urinary Tract Infections in the Ambulatory Setting.
A Phase 4 study testing Diclofenac and Norfloxacin in people with Urinary Tract Infections, run by Insel Gruppe AG, University Hospital Bern at 1 site in Switzerland.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 70 years, women only
- Conditions the study is for
- Urinary Tract Infections
- What is being tested?
- Diclofenac and Norfloxacin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 253 participants
- Where
- 1 siteSwitzerland
- Study dates
- Feb 2012to Jan 2015
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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)
Show all 16Show fewer
- 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)
Trial locations and contacts
1 site in 1 country.
Switzerland1 site
Institute for Infectious Diseases, University of Berne
Bern, 3010
About this study
Official title: Symptomatic Therapy of Uncomplicated Lower Urinary Tract Infections in the Ambulatory Setting. A Randomized, Double Blind Trial
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.
Read the 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.
- Conditions
- Urinary Tract Infections
- Being tested
- Diclofenac, Norfloxacin
- Keywords
- Urinary tract infections, Anti-bacterial agents
- Medical subject headings
- Urinary Tract Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DiclofenacDrug
Diclofenac retard 75mg twice daily for 3 days, followed by fosfomycin 3g single dose on day 4 if deemed necessary
NorfloxacinDrug
Norfloxacin 400mg twice daily for 3 days, followed by fosfomycin 3g single dose on day 4 if deemed necessary
| Study group | Role | What they receive |
|---|---|---|
| antibiotic | Active comparator | Norfloxacin for three days, followed by fosfomycin on day 4 if deemed necessary Receives: Drug: Norfloxacin |
| symptomatic | Experimental | Diclofenac retard for three days, followed by fosfomycin on day 4 if deemed necessary Receives: Drug: Diclofenac |
What is being measured
The primary outcome is the main question the study is designed to answer.
The proportion of patients with resolution of symptoms on day 4
Measured: one month
Secondary outcomes (11)
The proportion of patients ever on antibiotics between randomization at day 1 and follow-up at day 30
Measured: one month
The proportion of patients using single dose fosfomycin on day 4
Measured: one month
The proportion of patients with re-consultations because of UTI within 30 days
Measured: one month
The mean composite symptom scores on days 4, 7 and 30
Measured: one month
The proportion of patients with resolution of symptoms on day 7
Measured: one month
The proportion of patients with complete resolution of symptoms on days 4 and 7
Measured: one month
The time until resolution of symptoms
Measured: one month
The proportion of patients with adverse events
Measured: one month
Mean overall patient stratification
Measured: one month
Health-related quality of life on day 4
Measured: one month
Number of working days lost
Measured: one month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Dec 2009 (estimated)
- Study startFeb 2012
- Primary completionDec 2014
- Study completionJan 2015
Why it stopped: New power calculation (reduction of necessary patient number)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Urinary Tract InfectionsStudies of the same condition, open and under way.
- More trials run by Insel Gruppe AG, University Hospital BernThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 253 participants (actual)
Sponsor and investigators
- Lead sponsor
- Insel Gruppe AG, University Hospital Bern
- Sponsor type
- University, hospital or other
- Collaborators
- University of Bern, Clinic for Infectious Diseases, University Hospital Bern, Switzerland
- Responsible party
- Sponsor
- Investigators
- Andreas Kronenberg, Principal investigator, University of Bern
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01039545
- Sponsor's protocol ID
- 254/09
- Status last verified
- Jul 2015
- First submitted
- 24 Dec 2009
- Last updated
- 9 Jul 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
Sachdeva A, Rai BP, Veeratterapillay R, Harding C, Nambiar A. Non-steroidal anti-inflammatory drugs for treating symptomatic uncomplicated urinary tract infections in non-pregnant adult women. Cochrane Database Syst Rev. 2024 Dec 19;12(12):CD014762. doi: 10.1002/14651858.CD014762.pub2.
PubMed 39698942Kronenberg A, Butikofer L, Odutayo A, Muhlemann K, da Costa BR, Battaglia M, Meli DN, Frey P, Limacher A, Reichenbach S, Juni P. Symptomatic treatment of uncomplicated lower urinary tract infections in the ambulatory setting: randomised, double blind trial. BMJ. 2017 Nov 7;359:j4784. doi: 10.1136/bmj.j4784.
PubMed 29113968
Study at a glance
From the registry record, last updated by the sponsor on 9 Jul 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Symptomatic Therapy of Uncomplicated Lower Urinary Tract Infections in the Ambulatory Setting. A Randomized, Double Blind Trial
- ClinicalTrials.gov ID
- NCT01039545
- Acronym / sponsor ID
- 254/09
- Conditions
- Urinary Tract Infections
- Keywords
- Urinary tract infections, Anti-bacterial agents
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: New power calculation (reduction of necessary patient number)
- Enrolment
- 253 participants (actual)
- Lead sponsor
- Insel Gruppe AG, University Hospital BernUniversity, hospital or other
- Collaborators
- University of Bern, Clinic for Infectious Diseases, University Hospital Bern, Switzerland
- Study start
- Feb 2012
- Primary completion
- Dec 2014 (actual)
- Study completion
- Jan 2015 (actual)
- First posted
- 25 Dec 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| antibiotic | Active comparator | Drug: NorfloxacinNorfloxacin for three days, followed by fosfomycin on day 4 if deemed necessary |
| symptomatic | Experimental | Drug: DiclofenacDiclofenac retard for three days, followed by fosfomycin on day 4 if deemed necessary |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (16 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DiclofenacDiclofenac retard 75mg twice daily for 3 days, followed by fosfomycin 3g single dose on day 4 if deemed necessary | Drug | symptomatic |
| NorfloxacinNorfloxacin 400mg twice daily for 3 days, followed by fosfomycin 3g single dose on day 4 if deemed necessary | Drug | antibiotic |
Primary outcome
The proportion of patients with resolution of symptoms on day 4
Time frame: one month
11 secondary outcomes
The proportion of patients ever on antibiotics between randomization at day 1 and follow-up at day 30
Time frame: one month
The proportion of patients using single dose fosfomycin on day 4
Time frame: one month
The proportion of patients with re-consultations because of UTI within 30 days
Time frame: one month
The mean composite symptom scores on days 4, 7 and 30
Time frame: one month
The proportion of patients with resolution of symptoms on day 7
Time frame: one month
The proportion of patients with complete resolution of symptoms on days 4 and 7
Time frame: one month
The time until resolution of symptoms
Time frame: one month
The proportion of patients with adverse events
Time frame: one month
Mean overall patient stratification
Time frame: one month
Health-related quality of life on day 4
Time frame: one month
Number of working days lost
Time frame: one month
Results and safety
The study was stopped early (reason given: New power calculation (reduction of necessary patient number)). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jul 2015.
- Derived from this study: PubMed 39698942Sachdeva A, Rai BP, Veeratterapillay R, Harding C, Nambiar A. Non-steroidal anti-inflammatory drugs for treating symptomatic uncomplicated urinary tract infections in non-pregnant adult women. Cochrane Database Syst Rev. 2024 Dec 19;12(12):CD014762. doi: 10.1002/14651858.CD014762.pub2.
- Derived from this study: PubMed 29113968Kronenberg A, Butikofer L, Odutayo A, Muhlemann K, da Costa BR, Battaglia M, Meli DN, Frey P, Limacher A, Reichenbach S, Juni P. Symptomatic treatment of uncomplicated lower urinary tract infections in the ambulatory setting: randomised, double blind trial. BMJ. 2017 Nov 7;359:j4784. doi: 10.1136/bmj.j4784.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Andreas Kronenberg principal investigator
University of Bern
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Diclofenac and Norfloxacin in people with Urinary Tract Infections, run by Insel Gruppe AG, University Hospital Bern at 1 site in Switzerland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 9 Jul 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: New power calculation (reduction of necessary patient number)). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The proportion of patients with resolution of symptoms on day 4 (time frame: one month). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01039545, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jul 2015.