Clinical trial NCT05055544: Bearberry in the Treatment of Cystitis
Official title: BeaRberry in the Treatment of Acute UncoMplIcated Cystitis (BRUMI)- Protocol of a Multicentre, Randomized Double-Blind Clinical Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Cystitis
Keywords: bearberry
cystitis
uncomplicated cystitis
fosfomycin
Lead sponsor: University of Pecs
Sponsor class: OTHER
First posted: 2021-09-24
Enrollment: 504
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a randomized, controlled, double-blinded, two-armed multicentre trial.
Primary purpose: TREATMENT

Brief summary: The goal of this study is to assess the efficacy of bearberry in uncomplicated cystitis. Uncomplicated cystitis is a disease related to the infection of the urinary bladder. Typical symptoms are dysuria, urinary urgency, and frequent voiding of small volumes. Urinary tract infections are frequent in women, usually treated with antibiotics, since the disease is usually caused by bacteria.

Fosfomycin is a frequently used antibiotic for the treatment of uncomplicated cystitis. This medicine is typically prescribed by MDs. However, since uncomplicated cystitis is quite frequent, not all patients visit the doctor when experiencing the symptoms of this disease. The use of over-the-counter products (medicines and food supplements) to alleviate the symptoms is common. One of the most frequently used medicinal plants for this purpose is bearberry. Bearberry is a medicinal plant traditionally used for the treatment of cystitis. Its use is accepted by the European Medicine Agency as traditional herbal medicinal product for relief of symptoms of mild recurrent lower urinary tract infections such as burning sensation during urination and/or frequent urination in women. Although the experience gained during the traditional use and the laboratory experiments support the supposed beneficial effect of bearberry, its clinical efficacy has not been confirmed in well-designed clinical trials in comparison with standard antibiotic therapy. In this study, the efficacy of bearberry will be assessed in comparison with fosfomycin.

Premenopausal women experiencing the symptoms of uncomplicated cystitis will be randomly divided into two groups. Since it will be a double-blind trial, neither the participants nor the experimenters will know who is receiving a particular treatment. In group A, patients will receive a single dose of fosfomycin powder dissolved in water and 2 placebo tablets three times a day for 7 days. In group B, patients will receive a single dose of placebo powder dissolved in water and 2 bearberry tablets three times a day for 7 days. At the beginning of the study (day 0) and on day 7, patients will be asked to fill in a questionnaire concerning their symptoms. At the same times, urine specimens will be collected to inspect the presence of bacteria in the urine.

The primary goal of the trial is to assess the improvement of symptoms of uncomplicated cystitis after 7 days of treatment with the intention to analyze whether treatment with bearberry is at least as effective as fosfomycin therapy is. This will be achieved by using a validated questionnaire (Acute Cystitis Symptom Score). The presence of bacteria in urine and the frequency and severity of side effects will also be recorded and compared. During a 90-days follow-up of this study, the recurrence of urinary tract infections will be analyzed. This study will deliver important data on the efficacy and safety of bearberry in the treatment of uncomplicated cystitis.

Detailed description: This randomized, controlled double-blind multicentre trial will assess the non-inferiority of bearberry (Arctostaphylos uva-ursi) in comparison with fosfomycin in the therapy of uncomplicated cystitis.

In clinical practice, acute uncomplicated cystitis is usually treated based on the clinical signs and symptoms. According to current guidelines, first-line drugs are fosfomycin trometamol, nitrofurantoin, nitroxoline, trimethoprim-sulfamethoxazole, and pivmecillinam. The advantage of fosfomycin is that a single is considered to be sufficient for the treatment of uncomplicated cystitis, resulting in better patient compliance compared to other antibiotics.

Bacterial resistance is one of the major drawback of antibiotic use. Therefore, the assessment of other medicines than currently used antibiotics is of primary importance. One of the most widely used over-the-counter medications in the treatment of urinary tract infection-related symptoms is bearberry. Although this plant has been used in traditional medicine for the treatment of acute cystitis, and the European Medicines Agency acknowledged its use as traditional herbal medicinal product used for the treatment of symptoms of mild recurrent lower urinary tract infections such as burning sensation during urination and/or frequent urination in women, the efficacy has not been assessed in well-designed clinical trials. Since several patients are using bearberry-based medicines, it is important to obtain clinical data on the efficacy and safety of this plant. The aim of this study is to assess the non-inferiority of bearberry in comparison with a standard antibiotic (fosfomycin) used in acute uncomplicated cystitis.

Eligibility criteria: Inclusion Criteria:

* premenopausal adult women
* diagnosis of acute uncomplicated cystitis (with the symptoms of dysuria, increased frequency, and urgency of urination and lower abdominal pain (suprapubic pain), that is presumed to be confined to the bladder; with no signs or symptoms that suggest an upper tract or systemic infection)
* a sum-score of of ≥6 for the typical uncomplicated urinary tract infections symptoms (frequency, urgency, painful urination, incomplete emptying, suprapubic pain, and visible hematuria) reported on the Acute Cystitis Symptom Score (ACSS) typical domain and pyuria (10 white blood cells/mm3 in a mid-stream specimen) at day 0

Exclusion Criteria:

* any renal disease
* upper urinary tract infection
* malformations of the urinary tract
* congenital disorders of the urinary tract
* catheter use
* pregnancy
* breastfeeding
* self-medication with bearberry or antibiotic use in the last 3 months
* 5 or more bearberry treatments in the previous year
* concomitant use of other antibiotics and NSAIDs
* contraindication for study drugs
* active malignancy
* immunodeficiency, including immunosuppressive treatment.

Primary outcomes:
measure: Change of symptom severity
timeFrame: The 2 time points at which the measurement is assessed is the time of enrollment, after 7 days of treatment.
Secondary outcomes:
measure: Number of patients without significant urine pathogens
timeFrame: The time point at which the measurement is assessed on day 7.
measure: Number of urine pathogens
timeFrame: The time point at which the measurement is assessed on day 7.
measure: Frequency and severity of side effects
timeFrame: The time point at which the measurement is assessed on day 7.
measure: Recurrence of urinary tract infection (UTI)
timeFrame: The time point at which the measurement is assessed on day 90.
measure: Concurrent use of other medications
timeFrame: The time point at which the measurement is assessed on day 7.
Other outcomes:
Locations:
city: Pécs
country: Hungary
facility: Institute for Translational Medicine, University of Pécs
Study officials:
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