Reducing Antibiotic Use for Uncomplicated Urinary Tract Infection in General Practice by Treatment With Uva Ursi (UU)- a Comparative Effectiveness Trial

Study Overview
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Brief Summary
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It is well known that over-treatment of straightforward infections should be avoided as far as possible. Evidence-based data on non antibiotic treatment options for common conditions are therefore needed urgently. This randomised-controlled double blind trial examines whether initial herbal treatment with Uva Ursi, and antibiotic treatment only if symptoms persist, reduces antibiotic consumption in uncomplicated urinary tract infections (UTI) without a negative effect on symptom course and rate of recurrent UTIs. In total, 430 patients presenting with typical UTI symptoms will be included by their GPs and receive randomised either herbal treatment with uva ursi (antibiotics only if symptoms persist), or initial antibiotic treatment. Patients record symptom severity and drug intake in a diary and complete a final questionnaire after 28 days.

Official Title
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Reducing Antibiotic Use for Uncomplicated Urinary Tract Infection in General Practice by Treatment With Uva Ursi (UU)- a Comparative Effectiveness Trial

Conditions
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Urinary Tract Infections

Intervention / Treatment
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* Drug: Arctuvan
* Drug: Fosfomycin
* Drug: Placebo to Arctuvan
* Drug: Placebo to Fosfomycin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women (18-75 years) with suspected UTI at least two symptoms of UTI (dysuria, urgency of micturition, frequency, lower abdominal pain) Written informed consent Exclusion Criteria: signs of complicated UTI (e. g. temperature > 38°C, loin tenderness) conditions that may lead to complicated infections (i.e. renal diseases, patients with urinary catheter) pregnancy/ breastfeeding current self-medication with UU preparations e.g. z.B. Cystinol®, Uvalysat®, Arctuvan® antibiotic use in the last 7 days previous UTI in the past 2 weeks history of pyelonephritis contraindications for trial drugs serious diseases inability to understand trial Information current participation in another clinical trial or participation in another clinical trial within the last 4 weeks

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Uva Ursi<br>placebo to fosfomycin: 3 g granules orally 1x1 (day 0) and Uva Ursi: 105 mg (Arctuvan®) 3x2 tablets orally from day 0 for 5 days | Drug: Arctuvan<br>* application of a herbal drug<br>Drug: Placebo to Fosfomycin<br>* application of Placebo to Fosfomycin<br>|
| Active Comparator: fosfomycin<br>fosfomycin (Monuril®): 3 g granules orally 1x1 (day 0), and placebo to Uva Ursi: 3x2 tablets orally from day 0 for 5 days If the patient returns with persistent/recurrent symptoms, antibiotic therapy according to the sensitivity test. | Drug: Fosfomycin<br>* application of an antibiotic drug<br>Drug: Placebo to Arctuvan<br>* application of Placebo to Arctuvan<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| antibiotic courses | number of antibiotic courses from day 0 to day 28 | day 0-28 | 
| symptom burden | symptom burden (AUC) from day 0 to day 7 | day 0-7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| early relapses | number of early relapses until day 14 | day 0-14 | 
| recurrent UTI | number of recurrent UTI day 15-28 | day 15-28 | 
| symptom resolution | number of patients with symptom resolution on day 4/7 | day 4 and 7 | 
| symptom sum score by patients' questionnaire | mean daily symptom sum scores from day 0 to day 7; Each of the symptoms dysuria, urgency, frequency and lower abdominal pain is scored daily on a five point scale from 0 none to 4 very strong in a patients' questionnaire. | day 0-7 | 
| symptom burden for dysuria | symptom burden (AUC) for dysuria scored daily on a five point scale from 0 none to 4 very strong, from day 0 to day 7 | day 0-7 | 
| symptom burden positive urine culture | symptom burden (AUC) day 0-7 of patients with positive urine culture | day 0-7 | 
| symptom burden negative urine culture | symptom burden (AUC) day 0-7 of patients with negative urine culture | day 0-7 | 
| activity impairment by UTI symptoms, measured as AUC | activity impairment by UTI symptoms (days 0-7), measured as AUC. Impairment by each UTI symptom is scored daily on a five point scale from 0 none to 4 very strong. | day 0-7 | 
| painkillers | use of painkillers (Defined Daily Dose (DDD) day 0-7) | day 0-7 | 
| patients taking painkillers | number of patients taking painkillers | day 28 | 
| antibiotic use | antibiotic use (defined daily dose (DDD) day 0-28) | day 0-28 | 
| UTI related visits | number of UTI related visits day 0-28 | day 0-28 | 
| UTI related sick leave | number of days of UTI related sick leave day 0-28 | day 0-28 | 
| patients with poor outcome: temperature | number of patients with temperature >38°C, day 0-7, according to patients´ statement | day 0-7 | 
| patients with poor outcome: worsening symptoms | number of patients with worsening symptoms (impairment in symptom score) | day 28 | 
| patients with poor outcome: prolonged symptoms | number of patients with prolonged symptoms (> 7 days), day 0-28. Patients will be followed up until symptom resolution, defined as max. 1 score point on each symptom scale. | day 0-28 | 
| pyelonephritis | number of pyelonephritis day 0-28, according to GP´s diagnosis | day 0-28 | 
| AE and SAE | number of AE and SAE by system organ class day 0-28 | day 0-28 | 
| patients with at least 1 AE/ 2 AE | proportion of patients with at least 1 AE/ 2 AE | day 28 | 
| symptom burden for urgency | symptom burden (AUC) for urgency scored daily on a five point scale from 0 none to 4 very strong, from day 0 to day 7 | day 0-7 | 
| symptom burden for frequency | symptom burden (AUC) for frequency scored daily on a five point scale from 0 none to 4 very strong, from day 0 to day 7 | day 0-7 | 
| symptom burden for lower abdominal pain | symptom burden (AUC) for lower abdominal pain scored daily on a five point scale from 0 none to 4 very strong, from day 0 to day 7 | day 0-7 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Uva Ursi, fosfomycin, uncomplicated urinary tract infection of women