Clinical Assessment of Urinary Antiseptics Methenamine and Methylthioninium in Recurrent Cystitis

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.

Study Overview

• Status: Completed
• Conditions: Urinary Tract Infections
• Intervention / Treatment: Drug: Methenamine + Methylthioninium; Drug: Antibiotics; Drug: Methenamine + Methylthioninium + Acriflavine + Atropa belladona

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 284
• Phase: Phase 4

Contacts and Locations

Study Locations

• Brazil
  • RJ
    • Teresópolis, RJ, Brazil, 25964004
      • Centro Universitário Serra dos Órgãos - UNIFESO

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Methenamine + Methylthioninium; Dosage: Methenamine (120mg) + Methylthioninium (20mg) Dosage form: coated tablets Frequency: 2 coated tablets twice daily Duration: 6 days	Drug: Methenamine + Methylthioninium; Methenamine + Methylthioninium; Other Names: methenamine + methylene blue; Drug: Antibiotics; Antibiotics based on individual subjects urine culture / antibiogram; Other Names: Antimicrobials
Active Comparator: Methenamine+Methylthioninium+Acriflavine+Atropa belladona; 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: Antibiotics; Antibiotics based on individual subjects urine culture / antibiogram; Other Names: Antimicrobials; Drug: Methenamine + Methylthioninium + Acriflavine + Atropa belladona; Methenamine + Methylthioninium + Acriflavine + Atropa belladona; Other Names: methenamine + methylene blue + acriflavine + A. belladona

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Fundação Educacional Serra dos Órgãos
• Investigators: Principal Investigator: carlos p nunes, MD, Fundação Educacional Serra dos Órgãos

Study record dates

Study Major Dates

• Study Start (Actual): March 31, 2018
• Primary Completion (Actual): May 1, 2019
• Study Completion (Actual): June 1, 2021

Study Registration Dates

• First Submitted: December 8, 2017
• First Submitted That Met QC Criteria: December 14, 2017
• First Posted (Actual): December 20, 2017

Study Record Updates

• Last Update Posted (Actual): December 14, 2021
• Last Update Submitted That Met QC Criteria: November 29, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Urologic Diseases; Urinary Bladder Diseases; Cystitis; Urinary Tract Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents, Local; Anti-Infective Agents; Enzyme Inhibitors; Anti-Infective Agents, Urinary; Renal Agents; Anti-Bacterial Agents; Methylene Blue; Methenamine; Methenamine hippurate; Methenamine mandelate; Acriflavine
• Other Study ID Numbers: AUCR-01-05-17

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No