Optimization of Bacterial Vaginosis Treatment in Women of Reproductive Age

Bacterial Vaginosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06458543
• Other study ID #: Longidaza IMSechenovMMA
• Status: Recruiting
• Phase: Phase 4
• Start date: June 1, 2024
• Est. completion date: June 1, 2026

Study information

• Verified date: June 2024
• Source: I.M. Sechenov First Moscow State Medical University
• Contact: Leonid Spivak, MD, Prof.
• Phone: +7 (903) 749-05-97
• Email: leonid.spivak[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this clinical trial is to study the efficacy of bovgialuronidase azoximere in the treatment and duration of recurrence-free course of bacterial vaginosis in women of reproductive age. The main questions it aims to answer are:

• Is bovgialuronidase azoximer able to destroy G. vaginalis associated biofilms of the vaginal epithelium

• use of bovgialuronidase azoximer together with Metronidazole increases the effectiveness of treatment of bacterial vaginosis.

• use of azoximers bovgialuronidase together with Metronidazole increases the duration of relapse-free course of bacterial vaginosis.

Participants in the experimental and control group will be:

• Amsel criteria assessment

• Colpotest-PH (vaginal acidity)

• aminotest with 10% KOH solution ("fish odor")

• microscopic examination of vaginal discharge

• Bacteriologic culture of vaginal discharge

• Polymerase chain reaction of epithelial cell scrapings from the vagina

• electron microscopy of vaginal epithelial cell scrapings

Participants in the main group will be given the drug Bovgialuronidase azoximer and Metronidazole.

Participants in the control group: Metronidazole.

Researchers will compare the experimental and control groups to see if there are differences after treatment in biofilm structure, treatment efficacy, and duration of recurrence-free survival.

Description:

Bacterial vaginosis is characterized by a decrease in the number of lactobacilli and the dominance of opportunistic anaerobic flora (primarily G.vaginalis, to a lesser extent Atopobium vaginae, Peptostreptococcus, Clostridiales spp., Prevotella spp., etc.). Modern ideas of the pathogenesis of bacterial vaginosis consist in the formation of polymicrobial biofilms on the surface of the mucosa of the vaginal epithelium. Biofilms are a community of microorganisms of one or more species attached to the surface of a polymeric matrix. Biofilms are formed predominantly by G.vaginalis and to a lesser extent by other pathogens associated with bacterial vaginosis (Atopobium vaginae, Peptostreptococcus, Clostridiales spp., Prevotella spp., etc.). Biofilm-associated bacterial vaginosis is characterized by increased resistance to pathogenetic therapy, the ability to evade defense mechanisms and prolonged persistence in the vaginal environment. These features of pathogenesis cause a high rate of recurrences and chronic course of bacterial vaginosis.

Thus, it is relevant to study in vivo the role of drug action on biofilms to destroy them in order to increase the effectiveness of antibacterial therapy and reduce the frequency of recurrences of bacterial vaginosis.

The standard and approved by the Ministry of Health of the Russian Federation method of treatment of bacterial vaginosis is Metronidazole.

The aim of this clinical trial is to investigate the efficacy of combination therapy with metronidazole and azoximera bovgialuronidase in the treatment and duration of relapse-free course of bacterial vaginosis in women of reproductive age compared with metronidazole monotherapy.

The main questions it aims to answer are:

• Is bovgialuronidase azoximer able to destroy G. vaginalis associated biofilms of the vaginal epithelium

• use of bovgialuronidase azoximer together with Metronidazole increases the effectiveness of treatment of bacterial vaginosis.

• use of azoximers bovgialuronidase together with Metronidazole increases the duration of relapse-free course of bacterial vaginosis.

Participants in the experimental and control group will be:

• Amsel criteria assessment

• Colpotest-PH (vaginal acidity)

• aminotest with 10% KOH solution ("fish odor")

• microscopic examination of vaginal discharge

• Bacteriologic culture of vaginal discharge

• Polymerase chain reaction of epithelial cell scrapings from the vagina

• electron microscopy of vaginal epithelial cell scrapings

Main group - patients with bacterial vaginosis receiving pathogenetic antibacterial therapy (Metronidazole) in combination with Bovgialuronidase azoximer.

Control group - patients with bacterial vaginosis receiving pathogenetic antibacterial therapy (Metronidazole) without Bovgialuronidase azoximer.

Researchers will compare the experimental and control groups to see if there are differences after treatment in biofilm structure, treatment efficacy, and duration of recurrence-free survival.

Other known NCT identifiers

• NCT06453200

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: June 1, 2026
• Est. primary completion date: June 1, 2025
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 45 Years

Eligibility

Inclusion Criteria:

• The written informed consent of the patient to participate in the study;

• Age (18 - 45 years old);

• The established diagnosis of Bacterial vaginosis;

• Absence of pregnancy and lactation.

Exclusion Criteria:

• Refusal of the patient from further participation in the study;

• Lack of patient adherence to treatment;

• The occurrence of conditions and diseases related to the list of contraindications to the use of the studied drug during the study.

• The presence of Candida spp., Neisseria gonorrhoeae, Trichomonas vaginalis, confirmed by laboratory;

• The presence of contraindications to the use of the studied drug according to the instructions for the drug.

Related Conditions & MeSH terms

• Bacterial Vaginosis
• Vaginal Diseases
• Vaginosis, Bacterial

Intervention

Drug:
• Longidaza
Bovhyaluronidase azoximer, vaginal suppositories 3000 IU, 1 suppository vaginally every other day, course of 10 days
• Metronidazole 500 mg
Metronidazole, tablets 500 mg, 1 tablet 2 times a day, orally, course 7 days

Locations

Country	Name	City	State
Russian Federation	LLC "Family polyclinic No. 4" Korolev	Korolev
Russian Federation	I.M. Sechenov First Moscow State Medical University (Sechenov University)	Moscow

Sponsors (1)

Lead Sponsor	Collaborator
I.M. Sechenov First Moscow State Medical University

Country where clinical trial is conducted

Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Reduction in the number of relapses of bacterial vaginosis	Evaluated by clinical data (using Amsel criteria) and laboratory (microscopic examination - identification of "key cells"); The Amsel criteria include 4 parameters, each of which is scored as one point: gray/white/grayish-white vaginal discharge; Vaginal acidity pH greater than 4.5 (colpotest pH); aminotest with 10% solution of potassium hydroxide KOH (appearance of "fishy", "rotten" odor); Presence of "key cell" in microscopic examination of vaginal discharge; The presence of 3 or more of the 4 criteria speaks in favor of the diagnosis of "bacterial vaginosis" 2 and less points - absence of "bacterial vaginosis"	6 months after treatment
Secondary	changes in biofilm structure according to electron microscopy data	Biofilms are a cooperation of microorganisms of one or more species that are incorporated into a polymeric matrix consisting of proteins, polysaccharides and nucleic acids. Electron microscopy allows to evaluate the structure of the biofilm, to distinguish between lactobacilli and anaerobes (G. vaginalis, Atopobium vaginae, Peptostreptococcus, Clostridiales spp., Prevotella spp., etc.). The destructive effect of azoximers bovgialuronidase on biofilms leads to disruption of biofilm structure: formation of holes in its structure, reduction of its size (volume), release of bacteria from the biofilm structure. Metronidazole has a bactericidal effect on G. vaginalis, Atopobium vaginae, Peptostreptococcus, Clostridiales spp., Prevotella spp., etc., which is expressed in the reduction of CFU/ml.	21 days after treatment
Secondary	decrease in the severity of characteristic complaints in female patients with BV	The main complaints that patients with bacterial vaginosis present with are: vaginal discharge and unpleasant odor of vaginal discharge.; The Amsel criteria are used to objectively assess these complaints; The Amsel criteria include 4 parameters, each of which is scored as one point: gray/white/grayish-white vaginal discharge; Vaginal acidity pH greater than 4.5 (colpotest pH); aminotest with 10% solution of potassium hydroxide KOH (appearance of "fishy", "rotten" odor); Presence of "key cell" in microscopic examination of vaginal discharge; The presence of 3 or more of the 4 criteria speaks in favor of the diagnosis of "bacterial vaginosis" 2 and less points - absence of "bacterial vaginosis"; After treatment the patient is expected to have no characteristic complaints	21 days after treatment
Secondary	Decreased vaginal acidity	Normally, the acidity of the vagina is 4.5 or less (??=4,5 ?r less), meaning the vagina has an acidic environment.; The pH is measured with the Kolpotest-PH rapid test. After applying vaginal discharge to the indicator screen of the test strip, it is colored. The color obtained is compared with the indicator scale placed on the Colpotest-pH jar. If the pH is 4.5 or less, it is normal.; A pH result greater than 4.5 favors a diagnosis of bacterial vaginosis After treatment is expected to normalize vaginal acidity (pH = 4.5 or less)	21 days after treatment
Secondary	Normalization of the composition of the microflora of the urogenital tract	Normally, the vagina of women of reproductive age is dominated by Lactobacilli (80-100%). A decrease in lactobacilli or their absence leads to the dominance of opportunistic microorganisms (e.g., G.vaginalis, Atopobium vaginae, Peptostreptococcus, Clostridiales spp., Prevotella spp., etc.), which causes the appearance of complaints characteristic of bacterial vaginosis (vaginal discharge, unpleasant odor of vaginal discharge, itching, burning).; Microbiome is assessed by polymer chain reaction (Femoflor-16), which allows not only qualitative but also quantitative assessment of the composition of the vaginal microbiome.; After treatment, the number of opportunistic anaerobes is expected to decrease and the number of lactobacilli is expected to be dominant	21 days after treatment