Efficacy of Bovhyaluronidase Azoximer on Biofilms Destruction in the Urogenital Tract of the Patients With Recurrent Bacterial Vaginosis.

Bacterial vaginosis (BV) occupies one of the leading places in the structure of the of gynecologic morbidity. This syndrome affects from 26 to 29% of women of reproductive age. Bacterial vaginosis is a non-inflammatory syndrome based on the replacement of normal lactoflora by opportunistic microorganisms. The modern concept of pathogenesis of bacterial vaginosis is the formation of biofilms, mainly Gardnerella vaginalis, on the surface of the vaginal epithelium. Associated with biofilms bacterial vaginosis is characterized by increased resistance to pathogenetic therapy, ability to evade protective mechanisms and prolonged persistence in the vaginal environment, which is manifested by an increase in the rate of recurrent and chronic course.

In connection with the above described, it is relevant to study in vivo the role of drug action on biofilms in order to destroy them and, as a consequence, to increase the effectiveness of pathogenetic antibacterial therapy, reduce the frequency of BV recurrences and improve the quality of life of women. According to the local and international literature, there are various ways to affect biofilms, one of which is enzymatic destruction of the matrix. Bovgialuronidase azoximer was chosen as the study drug.

Study Overview

• Status: Recruiting
• Conditions: Bacterial Vaginosis
• Intervention / Treatment: Drug: Longidaza; Drug: Metronidazole

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Leonid Spivak, MD, PhD; Phone Number: +79037490597; Email: leonid.spivak@gmail.com

Study Locations

• Russian Federation
  • Moscow, Russian Federation, 119991
    • Recruiting
    • Sechenov University.
    • Contact: Dmitry Enikeev, MD; Phone Number: +7 925 517 79 26; Email: enikeev-dv@1msmu.ru

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• availability of written informed consent to participate in the study
• age (18-45 years)
• established clinically (Amsel criteria) and laboratory (microscopic examination and PCR diagnosis of vaginal discharge) diagnosis of bacterial vaginosis

Exclusion Criteria:

• patient refusal to further participate in the study
• lack of patient adherence to treatment
• pregnancy and lactation
• the occurrence during the study of conditions and diseases that are included in the list of contraindications to the use of the drug being studied
• presence of Candida albicans, diplococci, trichomanas), confirmed by microscopic examination and PCR diagnostics
• presence of contraindications to the use of study drugs according to the instructions

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental; women aged 18 to 45 years with bacterial vaginosis receiving pathogenetic antibacterial therapy with drugs from the groups of nitroimidazole derivatives/lincosamides (Metronidazole) with Bovgialuronidase azoximer.	Drug: Longidaza; - Bovgialuronidase azoximer (Longidaza), vaginal suppositories, 3000 IU, 1 suppository every other day vaginally for 10 days.; Drug: Metronidazole; - Metronidazole, tablets, 500 mg, 1 tablet 2 times a day, treatment duration 7 days;
Active Comparator: Control; women 18 to 45 years of age with bacterial vaginosis, receiving pathogenetic antibacterial therapy with preparations from the nitroimidazole/lincosamide derivative groups (Metronidazole) without the use of azoximer bovgialuronidase.	Drug: Metronidazole; - Metronidazole, tablets, 500 mg, 1 tablet 2 times a day, treatment duration 7 days;

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
reducing the number of recurrences of bacterial vaginosis	clinically (absence of complaints - assessed using Amel criteria), laboratory (absence of key cells according to microscopic examination, predominance of lactobacilli over opportunistic flora (lactobacteria 80-100%) - PCR diagnostics Femoflor 16), pH less than 4.5 (colpotest - pH), negative amino test with 10% KOH solution	21 days, 6 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
disruption of biofilm structure and decrease in the number of colony-forming units of opportunistic anaerobes (G. vaginalis, Atopobium vaginae) according to electron microscopy	electron microscopy allows, under high magnification, to determine the presence of biofilms and their structure, as well as microorganisms included in the biofilm (due to the destructive effect of azoximer bovgialuronidase on biofilms and direct pathogenetic effect of Metronidazole on G. vaginalis, Atopobium vaginae). vaginalis, Atopobium vaginae)	21 days
reduction of characteristic complaints in women with bacterial vaginosis (Amsel criteria)	gray or gray-white vaginal discharge, "key cells" according to microscopic examination of vaginal secretions, pH more than 4.5 (colpotest-pH), positive aminotest with 10% potassium hydroxide solution - each of the four signs is rated 1 point	21 days
decrease in vaginal acidity (Kolpotest-pH test strips)	vaginal acidity (рН) = 4,5 and less than 4,5	21 days
absence of key cells according to microscopic examination of vaginal discharge	key cells according to microscopic examination of vaginal discharge are characteristic of bacterial vaginosis	21 days
dominance of lactobacilli over opportunistic anaerobic flora, expressed as a percentage and 10Lg (PCR diagnosis - Femoflor-16)	bacterial vaginosis is a non-inflammatory syndrome, where the normal vaginal microflora (lactobacteria) is replaced by opportunistic flora (G. vaginalis, A. vaginae, etc.) with the dominance of the latter. Normally, lactobacilli dominate in the vagina (80-100%)	21 days

Collaborators and Investigators

• Sponsor: I.M. Sechenov First Moscow State Medical University

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2024
• Primary Completion (Estimated): June 1, 2025
• Study Completion (Estimated): June 1, 2026

Study Registration Dates

• First Submitted: June 7, 2024
• First Submitted That Met QC Criteria: June 7, 2024
• First Posted (Actual): June 11, 2024

Study Record Updates

• Last Update Posted (Actual): June 11, 2024
• Last Update Submitted That Met QC Criteria: June 7, 2024
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Bacterial Vaginosis; bovhyaluronidase azoximer; biofilms
• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Vaginitis; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Vaginal Diseases; Vaginosis, Bacterial; Anti-Infective Agents; Anti-Bacterial Agents; Antiprotozoal Agents; Antiparasitic Agents; Metronidazole
• Other Study ID Numbers: Sechenov-Bovhyaluronidase

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
• product manufactured in and exported from the U.S.: No