Vaginal Ovule With Flavonoid Tea Extract for the Correction of Imbalance in the Vaginal Environment

Study Overview
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Brief Summary
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Randomized, blinded vehicle-controlled multicenter clinical trial (MAT072017) to determine the effect of vaginal ovules containing 2 mg of the tea extract Matuzalem on the subjective symptoms (5-point scale pruritus (itching), dolor (pain), rubor (redness), fluor (discharge), and fetor (odor)), and objective symptoms (pH, Nugent score) of bacterial vaginosis. An ovule containing only the vehicle (polyethylene glycol 3000 S) was used as a control. The study was blinded from the perspective of the subject, investigator, laboratory personnel and data analyst.

Detailed Description
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The objective was to determine whether vaginal ovule with tea extract once-daily for 5-7 days improves symptoms of intermediate vaginal flora and prevents the development of bacterial vaginosis. Composite primary endpoint designed as a drop in the Nugent score, vaginal pH, or improvement of subjective symptoms was compared between the active and vehicle (polyethylene-glycol) arm after 7 days of application and following 7 days after the application. Secondary outcome measures were (1) Correction of the vaginal environment (as previously defined) 7 days after the completion of the prescribed 7-day regimen (day 14); (2) change in each parameter separately; (3) change in individual subjective symptoms, (4) exploratory analysis of the microbial environment at each subject visit. The study was approved and supervised by the National authority and Ethics committee and prospectively registered in the Czech national medical device trial registry RZPRO and the European medical device trial registry EUDAMED.

Official Title
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Medical Device Matuzalem Flavonoid Tea Extract Vaginal Ovule for the Correction of the Imbalance in the Vaginal Environment- Prospective, Multicentric, Two-arm, Randomized, Vehicle-controlled, Blinded, Comparative Clinical Trial

Conditions
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Vaginosis, Bacterial, Vaginal Flora Imbalance

Intervention / Treatment
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* Device: Matuzalem ovule
* Device: Vehicle ovule


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: premenopausal participants disturbed vaginal environment not in need of antibiotic or antimycotic treatment participants were citizens of the Czech Republic age between 18 and 55 years either a vaginal pH > 4.5 or/and vaginal discomfort able to follow the prescribed regimen informed consents prior to any intervention, including diagnostic procedures. Exclusion Criteria: no vaginal bleeding of unknown aetiology hypersensitivity pregnancy lactation period during enrollment antibiotics in the previous 30 days treated with any products with similar indication acute urogenital infection diabetes mellitus advanced oncologic disease participant to other trial Nugent score above 6

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Female

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
Interventional Model Description: vehicle-controlled two-arm
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Matuzalem<br>Tea extract vaginal ovule daily for 7 consecutive days | Device: Matuzalem ovule<br>* vaginal ovule with 2 mg tea extract<br>|
| Sham Comparator: Vehicle<br>Polyethylene glycol vaginal ovule daily for 7 consecutive days | Device: Vehicle ovule<br>* polyethylene glycol vaginal ovule<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite endpoint (vaginal pH, Nugent score, subjective symptoms via questionnaire) after treatment completion | Correction of the vaginal environment after 7 days of once-daily application of the ovule was defined as: a drop-in Nugent score to < 4 and/or a drop in vaginal pH to < 4.5, or a subjective improvement in at least 2 symptoms by at least 2 points on a 5-point scale in patients whose baseline pH was < 4.5 and NS < 4. Subjective symptoms: Pruritus, dolor, rubor, fluor and fetor reported by the patient on 5-point scale (0=no problem to 4=severe problem) | following 7 days of the ovule daily application | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite endpoint (vaginal pH, Nugent score, subjective symptoms via questionnaire) after 7 days since treatment completion | Correction of the vaginal environment after 7 days after treatment completion defined as: a drop-in NS to < 4 and/or a drop in vaginal pH to < 4.5, or a subjective improvement in at least 2 symptoms by at least 2 points on a 5-point scale in patients whose baseline pH was < 4.5 and NS < 4. Subjective symptoms: Pruritus, dolor, rubor, fluor and fetor reported by the patient on 5-point scale (0=no problem to 4=severe problem) | 7 days after the completion of the 7-day treatment | 
| Change in the pH alone after treatment completion | Correction of the pH measured via pH strips | following 7 days of the ovule daily application | 
| Change in the Nugent score alone after treatment completion | Nugent score determined under 1000x magnification | following 7 days of the ovule daily application | 
| Change in the subjective symptoms (questionnaire) after treatment completion | Pruritus, dolor, rubor, fluor and fetor reported by the patient on 5-point scale (0=no problem to 4=severe problem) | following 7 days of the ovule daily application | 
| Change in the pH alone after 7 days since treatment completion | Correction of the pH measured via pH strips | 7 days after the completion of the 7-day treatment | 
| Change in the Nugent score alone 7 days after treatment completion | Nugent score determined under 1000x magnification | 7 days after the completion of the 7-day treatment | 
| Change in the subjective symptoms (questionnaire) 7 days after treatment completion | Pruritus, dolor, rubor, fluor and fetor reported by the patient on 5-point scale (0=no problem to 4=severe problem) | 7 days after the completion of the 7-day treatment | 
| Exploratory analysis of the microbial environment after treatment completion: squamous epithelial cells | Quantification of: squamous epithelial cells under 1000x magnification | following 7 days of the ovule daily application | 
| Exploratory analysis of the microbial environment after 7 days after treatment completion: squamous epithelial cells | Quantification of: squamous epithelial cells under 1000x magnification | 7 days after the completion of the 7-day treatment | 
| Exploratory analysis of the microbial environment after treatment completion: clue cells | Quantification of clue cells under 1000x magnification | following 7 days of the ovule daily application | 
| Exploratory analysis of the microbial environment after 7 days after treatment completion: clue cells | Quantification of clue cells under 1000x magnification | 7 days after the completion of the 7-day treatment | 
| Exploratory analysis of the microbial environment after treatment completion: mixed flora | Quantification of mixed flora under 1000x magnification | following 7 days of the ovule daily application | 
| Exploratory analysis of the microbial environment after 7 days after treatment completion: mixed flora | Quantification of mixed flora under 1000x magnification | 7 days after the completion of the 7-day treatment | 
| Exploratory analysis of the microbial environment after treatment completion: yeast as pseudomycelia | Quantification of yeast as pseudomycelia under 1000x magnification | following 7 days of the ovule daily application | 
| Exploratory analysis of the microbial environment after 7 days after treatment completion: yeast as pseudomycelia | Quantification of yeast as pseudomycelia under 1000x magnification | 7 days after the completion of the 7-day treatment | 
| Exploratory analysis of the microbial environment after treatment completion: Gram negative diplococci | Quantification of: Gram negative diplococci under 1000x magnification | following 7 days of the ovule daily application | 
| Exploratory analysis of the microbial environment after 7 days after treatment completion: Gram negative diplococci | Quantification of: Gram negative diplococci under 1000x magnification | 7 days after the completion of the 7-day treatment | 
| Exploratory analysis of the microbial environment after treatment completion: fibrous Lactobacillus | Quantification of: fibrous Lactobacillus under 1000x magnification | following 7 days of the ovule daily application | 
| Exploratory analysis of the microbial environment after 7 days after treatment completion: fibrous Lactobacillus | Quantification of: fibrous Lactobacillus under 1000x magnification | 7 days after the completion of the 7-day treatment | 
| Exploratory analysis of the microbial environment after treatment completion: Gardnerella | Quantification of: Gardnerella under 1000x magnification | following 7 days of the ovule daily application | 
| Exploratory analysis of the microbial environment after 7 days after treatment completion: Gardnerella | Quantification of: Gardnerella under 1000x magnification | 7 days after the completion of the 7-day treatment | 
| Exploratory analysis of the microbial environment after treatment completion: spirochetes | Quantification of: spirochetes under 1000x magnification | following 7 days of the ovule daily application | 
| Exploratory analysis of the microbial environment after 7 days after treatment completion: spirochetes | Quantification of: spirochetes under 1000x magnification | 7 days after the completion of the 7-day treatment | 
| Exploratory analysis of the microbial environment after treatment completion: parabasal epithelial cells | Quantification of: parabasal epithelial cells under 1000x magnification | following 7 days of the ovule daily application | 
| Exploratory analysis of the microbial environment after 7 days after treatment completion: parabasal epithelial cells | Quantification of: parabasal epithelial cells under 1000x magnification | 7 days after the completion of the 7-day treatment | 
| Exploratory analysis of the microbial environment after treatment completion: leukocytes | Quantification of: leukocytes under 1000x magnification | following 7 days of the ovule daily application | 
| Exploratory analysis of the microbial environment after 7 days after treatment completion: leukocytes | Quantification of: leukocytes under 1000x magnification | 7 days after the completion of the 7-day treatment | 
| Exploratory analysis of the microbial environment after treatment completion: yeast as blastospores | Quantification of: yeast as blastospores under 1000x magnification | following 7 days of the ovule daily application | 
| Exploratory analysis of the microbial environment after 7 days after treatment completion: yeast as blastospores | Quantification of: yeast as blastospores under 1000x magnification | 7 days after the completion of the 7-day treatment | 
| Exploratory analysis of the microbial environment after treatment completion: Gram pos. cocci in chains | Quantification of: Gram pos. cocci in chains under 1000x magnification | following 7 days of the ovule daily application | 
| Exploratory analysis of the microbial environment after 7 days after treatment completion: Gram pos. cocci in chains | Quantification of: Gram pos. cocci in chains under 1000x magnification | 7 days after the completion of the 7-day treatment | 
| Exploratory analysis of the microbial environment after treatment completion: Lactobacillus | Quantification of: Lactobacillus under 1000x magnification | following 7 days of the ovule daily application | 
| Exploratory analysis of the microbial environment after 7 days after treatment completion: Lactobacillus | Quantification of: Lactobacillus under 1000x magnification | 7 days after the completion of the 7-day treatment | 
| Exploratory analysis of the microbial environment after treatment completion: Mobilincus | Quantification of: Mobilincus under 1000x magnification | following 7 days of the ovule daily application | 
| Exploratory analysis of the microbial environment after 7 days after treatment completion: Mobilincus | Quantification of: Mobilincus under 1000x magnification | 7 days after the completion of the 7-day treatment | 
| Exploratory analysis of the microbial environment after treatment completion: Leptotrichia | Quantification of: Leptotrichia under 1000x magnification | following 7 days of the ovule daily application | 
| Exploratory analysis of the microbial environment after 7 days after treatment completion: Leptotrichia | Quantification of: Leptotrichia under 1000x magnification | 7 days after the completion of the 7-day treatment | 
| Exploratory analysis of the microbial environment after treatment completion: Trichomonas vaginalis | Quantification of: Trichomonas vaginalis under 1000 magnification | following 7 days of the ovule daily application | 
| Exploratory analysis of the microbial environment after 7 days after treatment completion: Trichomonas vaginalis | Quantification of: Trichomonas vaginalis under 1000 magnification | 7 days after the completion of the 7-day treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tea, Polyphenols, Nugent score, Antioxidants, Vaginal pH, complementary medicine