Clinical Assessment of Urinary Antiseptics Methenamine and Methylthioninium in Recurrent Cystitis

Study Overview
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Brief Summary
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This is a double-blind, randomized, double-dummy, comparative study in parallel groups of subjects presenting with recurrent cystitis (≥2 episodes within the past 6 months). Subjects will be randomized and treated with one of two presentations of urinary antiseptics containing methenamine and methylthioninium for three days, followed by three days of antibiotic therapy as determined by urine culture and antibiogram. This study aims to assess the efficacy and safety of each treatment.

Detailed Description
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This is a double-blind, randomized, double-dummy, comparative study in parallel groups of subjects presenting with recurrent cystitis (≥2 episodes within the past 6 months). After initial evaluations including urine culture and antibiogram, a total of 284 subjects will be randomized and treated with one of two presentations of urinary antiseptics containing methenamine and methylthioninium for six days. After three days of treatment, subjects will return to the study center and antibiotic therapy based on the results of the urine culture and antibiogram will be initiated for each subject, to be continued for the remaining three days of the treatment period. Efficacy assessments will include the UTISA (Urinary Tract Infection Symptoms Assessment Questionnaire) together with a global assessment by the investigator. Safety assessments will include monitoring of adverse events and laboratory tests carried out at each of the three study visits.

Official Title
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Clinical Assessment of Urinary Antiseptics Methenamine and Methylthioninium in Recurrent Cystitis

Conditions
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Urinary Tract Infections

Intervention / Treatment
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* Drug: Methenamine + Methylthioninium
* Drug: Methenamine + Methylthioninium + Acriflavine + Atropa belladona
* Drug: Antibiotics


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients of both sexes, age ≥18 Clinical diagnosis of recurrent cystitis (≥ 2 episodes in the past 6 months) Female subject of reproductive age not pregnant, agrees to use birth control during study period Subject has read, understood, signed and dated informed consent document Exclusion Criteria: History of nephritis or kidney stones History of hepatic or gastrointestinal disease Diabetes Glaucoma Female subjects: pregnancy or breastfeeding History of anatomical alterations contributing to recurring cystitis on imaging exams Hypersensitivity to any component of study drug

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Methenamine + Methylthioninium<br>Dosage: Methenamine (120mg) + Methylthioninium (20mg) Dosage form: coated tablets Frequency: 2 coated tablets twice daily Duration: 6 days | Drug: Methenamine + Methylthioninium<br>* Methenamine + Methylthioninium<br>* Other names: methenamine + methylene blue;Drug: Antibiotics<br>* Antibiotics based on individual subjects urine culture / antibiogram<br>* Other names: Antimicrobials;|
| Active Comparator: Methenamine+Methylthioninium+Acriflavine+Atropa belladona<br>Dosage: Methenamine (250mg) + Methylthioninium (20mg) + Acriflavine hydrochloride (15mg) + Atropa belladonna L. (15mg) Dosage form: coated tablets Frequency: 2 coated tablets twice daily Duration: 6 days | Drug: Methenamine + Methylthioninium + Acriflavine + Atropa belladona<br>* Methenamine + Methylthioninium + Acriflavine + Atropa belladona<br>* Other names: methenamine + methylene blue + acriflavine + A. belladona;Drug: Antibiotics<br>* Antibiotics based on individual subjects urine culture / antibiogram<br>* Other names: Antimicrobials;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Urination regularity | Percentage of subjects presenting improvement in cystitis symptoms in the Urination Regularity domain of the UTISA at Visit 2. | Following three days of treatment with urinary antiseptics | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total UTISA score | Evolution of total UTISA score at end of study compared to pretreatment in each treatment group | From pretreatment to final visit, total of 6 days of treatment | 
| UTISA question # 9 | Percentage of subjects with improvement in UTISA question 9 at Visit 2 in each treatment group | At Visit 2, after 3 days of treatment | 
| Adverse events | Incidence of study drug-related adverse events in each treatment group | From pretreatment to final visit, total of 6 days of treatment | 
| Problems with Urination at Visit 2 | Evolution of UTISA domain Problems with Urination in each treatment Group | After 3 days of treatment | 
| Problems with Urination at Visit 3 | Evolution of UTISA domain Problems with Urination in each treatment Group | After 6 days of treatment | 
| Pain Associated with UTI at Visit 2 | Evolution of UTISA domain Pain Associated with UTI in each treatment Group | After 3 days of treatment | 
| Pain Associated with UTI at Visit 3 | Evolution of UTISA domain Pain Associated with UTI in each treatment Group | After 6 days of treatment | 
| Blood in Urine at Visit 2 | Evolution of UTISA domain Blood in Urine in each treatment Group | After 3 days of treatment | 
| Blood in Urine at Visit 3 | Evolution of UTISA domain Blood in Urine in each treatment Group | After 6 days of treatment |