Vaginal Ovule With Flavonoid Tea Extract for the Correction of Imbalance in the Vaginal Environment (MAT072017)

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

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.

Study Overview

• Status: Completed
• Conditions: Vaginosis, Bacterial; Vaginal Flora Imbalance
• Intervention / Treatment: Device: Matuzalem ovule; Device: Vehicle ovule

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 274
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Czechia
  • Czech Republic
    • Brno, Czech Republic, Czechia, 60200
      • Centrum ambulantní gynekologie a primární péče, s.r.o.
    • Kladno, Czech Republic, Czechia, 27201
      • MUDr. Milan Kučera. s.r.o.
    • Odolena Voda, Czech Republic, Czechia, 25070
      • MUDr. Eva Novotná - FEMCARE s.r.o.
    • Prague, Czech Republic, Czechia, 15500
      • Mediva s.r.o.
    • Prague, Czech Republic, Czechia, 11000
      • OB/GYN Associates, s.r.o.
    • Prague, Czech Republic, Czechia, 12000
      • MediStar s.r.o.
    • Prague, Czech Republic, Czechia, 12800
      • MUDr. Michal Jelšík
    • Prague, Czech Republic, Czechia, 147000
      • Gyn Por Ivf MUDr. Samer Asad s.r.o.
    • Prague, Czech Republic, Czechia, 16000
      • Gynekologie Studentsky dum s.r.o.
    • Prague, Czech Republic, Czechia, 16000
      • LEVRET s.r.o.
    • Prague, Czech Republic, Czechia, 16100
      • T.B. Gyn s.r.o.
    • Prague, Czech Republic, Czechia, 16500
      • Gynelav s.r.o.
    • Prague, Czech Republic, Czechia
      • GYNEDAN s.r.o.
    • Tábor, Czech Republic, Czechia, 39003
      • MUDr.Tereza Šmrhová-Kovács

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Matuzalem; Tea extract vaginal ovule daily for 7 consecutive days	Device: Matuzalem ovule; vaginal ovule with 2 mg tea extract
SHAM_COMPARATOR: Vehicle; Polyethylene glycol vaginal ovule daily for 7 consecutive days	Device: Vehicle ovule; polyethylene glycol vaginal ovule

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Value Outcomes Ltd.
• Collaborators: Matuzalem.com-cz, s.r.o.
• Investigators: Study Director: Tomáš Doležal, MD et PhD, Value Outcomes Ltd.; Study Chair: Luboš Chadim, MVDr, Matuzalem.com-cz, s.r.o.

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 4, 2017
• Primary Completion (ACTUAL): May 9, 2018
• Study Completion (ACTUAL): May 9, 2018

Study Registration Dates

• First Submitted: November 13, 2019
• First Submitted That Met QC Criteria: November 18, 2019
• First Posted (ACTUAL): November 21, 2019

Study Record Updates

• Last Update Posted (ACTUAL): November 21, 2019
• Last Update Submitted That Met QC Criteria: November 18, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Keywords: Antioxidants; complementary medicine; Polyphenols; Vaginal pH; Nugent score; Tea
• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Vaginal Diseases; Vaginitis; Vaginosis, Bacterial
• Other Study ID Numbers: MAT072017

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Secondary analyses in progress

Drug and device information, study documents

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