Bacterial Vaginosis, Vaginal Infection, Vaginal Diseases
Conditions
Keywords
bacterial vaginosis, dequalinium chloride, metronidazole, vaginal infection treatment, comparative study, non inferiority
Brief summary
The goal of this clinical trial is to show the efficacy and safety of dequalinium chloride in the treatment of bacterial vaginosis compared to metronidazole.
Detailed description
Eligible patients who signed informed consent were randomized to receive treatment with either dequalinium chloride (+ oral placebo) or metronidazole (+ vaginal placebo) for up to 7 days. Primary objective was clinical cure rate at one week after start of treatment. Control visits to assess outcomes were done after end of treatment and after one month.
Interventions
Fluomizin vaginal tablets (10 mg dequalinium chloride) used once a day for 6 days
Metronidazole oral tablets (500 mg) taken twice a day for 7 days
Sponsors
Medinova AG
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Premenopausal woman ≥18 years 2. Diagnosis of bacterial vaginosis (all 4 Amsel criteria positive, i.e. 1) greyish white thin discharge, 2) postassium hydroxide (KOH) test or 'fishy' smell, 3) microscopic presence of \> 20% clue cells, 4) vaginal pH \> 4.5) 3. Signed Written Informed Consent to participate in this study
Exclusion criteria
1. Pregnancy and/or lactation based on urine Pregnancy test (women with childbearing potential should use any contraception excluding vaginal methods like vaginal ring, etc.) 2. Uterine bleeding (including menstruation) or vaginal bleeding of unknown origin 3. Ulcerations/erosions of vaginal mucosa or cervix uteri 4. Patients with clinical symptoms and findings of Candida vulvovaginitis and/or Aerobic vaginitis 5. Clinically manifest or suspicion of sexually transmitted infections (Neisseria gonorrhoeae, Chlamydia trachomatis, or Trichomonas vaginalis) based on signs, symptoms, and anamnesis 6. Use of any antimicrobial treatment (local or systemic) 14 days before entry the study 7. Use of any vaginal medication or vaginal douching 7 days before entry the study 8. Unwillingness to refrain from alcohol consumption during treatment, and 48 hours after treatment 9. Severe systemic diseases (HIV, cancer, tuberculosis, autoimmune diseases, diabetes mellitus, severe psychiatric conditions, etc.), including diseases treated with immunosuppressive therapies, systemic corticosteroids, or warfarin 10. Known or suspected hypersensitivity to one of the study medications, inclusive of their excipients 11. Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc. of the participant (including inability to fill-in electronic patient diary) 12. Participation of patient in another investigational drug study concomitantly or within 30 days prior to entry in the study 13. Patient is relative of, or staff directly reporting to, the investigator
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Cure Rate | One week after randomization (C1) | Resolution of the abnormal vaginal discharge, negative whiff test, and less than 20% clue cells |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Cure Rate | One month after randomization (C2) | Resolution of the abnormal vaginal discharge, negative whiff test, and less than 20% clue cells |
| Bacteriological Cure Rate | One week & one month | Nugent score ≤3 Nugent score uses a 0 - 10 scale (higher score mean a worse outcome): 0 - 3 = normal flora, 4 - 6 = intermediate flora, 7 - 10 = bacterial vaginosis |
| Therapeutic Cure | One week & one month | Combination of clinical and bacteriological cure |
| Subjective Assessment of Efficacy | One week | Efficacy was assessed by patients and investigators as 'very good', 'good', 'moderate' or 'poor'. |
| Subjective Assessment of Tolerability | One week | Tolerability was assessed by patients as 'very good', 'good', 'moderate' or 'poor'. |
Countries
Czechia, Poland, Slovakia
Participant flow
Recruitment details
Recruitment period: July 2021 to August 2022
Participants by arm
| Arm | Count |
|---|---|
| Dequalinium Chloride Dequalinium chloride 10 mg vaginal tablets
Dequalinium Chloride: Fluomizin vaginal tablets (10 mg dequalinium chloride) used once a day for 6 days | 72 |
| Metronidazole Metronidazole 500 mg oral tablets
Metronidazole Oral: Metronidazole oral tablets (500 mg) taken twice a day for 7 days | 75 |
| Total | 147 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lack of Efficacy | 0 | 1 |
| Overall Study | Not treated with study medication | 1 | 3 |
| Overall Study | Protocol Violation | 1 | 2 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Total | Dequalinium Chloride | Metronidazole |
|---|---|---|---|
| Age, Continuous | 36.7 years STANDARD_DEVIATION 9 | 36 years STANDARD_DEVIATION 9.2 | 37.5 years STANDARD_DEVIATION 8.9 |
| Nugent Score Bacterial vaginosis | 80 Participants | 39 Participants | 41 Participants |
| Nugent Score Intermediate | 25 Participants | 15 Participants | 10 Participants |
| Nugent Score Missing score | 1 Participants | 0 Participants | 1 Participants |
| Nugent Score Normal | 41 Participants | 18 Participants | 23 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 147 Participants | 72 Participants | 75 Participants |
| Sex: Female, Male Female | 147 Participants | 72 Participants | 75 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
| Vaginal infections in the last 12 months | 1 events | 1.0 events | 0 events |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 72 | 0 / 75 |
| other Total, other adverse events | 4 / 72 | 10 / 75 |
| serious Total, serious adverse events | 0 / 72 | 0 / 75 |
Outcome results
Primary
Clinical Cure Rate
Resolution of the abnormal vaginal discharge, negative whiff test, and less than 20% clue cells
Time frame: One week after randomization (C1)
Population: Patients who were randomized, treated, and with primary outcome data available
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dequalinium Chloride | Clinical Cure Rate | 64 Participants |
| Metronidazole | Clinical Cure Rate | 69 Participants |
Comparison: The outcome measure of the primary objective was a noninferiority margin of 15 percentage points in the absolute difference in clinical cure rates between dequalinium chloride and metronidazole 7 to 11 days after start of treatment.p-value: <0.025Farrington-Manning test
Secondary
Bacteriological Cure Rate
Nugent score ≤3 Nugent score uses a 0 - 10 scale (higher score mean a worse outcome): 0 - 3 = normal flora, 4 - 6 = intermediate flora, 7 - 10 = bacterial vaginosis
Time frame: One week & one month
Population: Some patients were missing the Nugent score
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dequalinium Chloride | Bacteriological Cure Rate | Visit 2 (1 month) | 28 Participants |
| Dequalinium Chloride | Bacteriological Cure Rate | Visit 1 (1 week) | 35 Participants |
| Metronidazole | Bacteriological Cure Rate | Visit 1 (1 week) | 51 Participants |
| Metronidazole | Bacteriological Cure Rate | Visit 2 (1 month) | 38 Participants |
Secondary
Clinical Cure Rate
Resolution of the abnormal vaginal discharge, negative whiff test, and less than 20% clue cells
Time frame: One month after randomization (C2)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dequalinium Chloride | Clinical Cure Rate | 55 participants |
| Metronidazole | Clinical Cure Rate | 62 participants |
Secondary
Subjective Assessment of Efficacy
Efficacy was assessed by patients and investigators as 'very good', 'good', 'moderate' or 'poor'.
Time frame: One week
Population: Many missing values
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Dequalinium Chloride | Subjective Assessment of Efficacy | Investigator | Poor | 1 Participants |
| Dequalinium Chloride | Subjective Assessment of Efficacy | Patient | Very Good | 19 Participants |
| Dequalinium Chloride | Subjective Assessment of Efficacy | Patient | Moderate | 4 Participants |
| Dequalinium Chloride | Subjective Assessment of Efficacy | Patient | Poor | 1 Participants |
| Dequalinium Chloride | Subjective Assessment of Efficacy | Investigator | Very Good | 46 Participants |
| Dequalinium Chloride | Subjective Assessment of Efficacy | Investigator | Good | 18 Participants |
| Dequalinium Chloride | Subjective Assessment of Efficacy | Investigator | Moderate | 4 Participants |
| Dequalinium Chloride | Subjective Assessment of Efficacy | Patient | Good | 26 Participants |
| Metronidazole | Subjective Assessment of Efficacy | Patient | Poor | 0 Participants |
| Metronidazole | Subjective Assessment of Efficacy | Investigator | Poor | 1 Participants |
| Metronidazole | Subjective Assessment of Efficacy | Investigator | Good | 20 Participants |
| Metronidazole | Subjective Assessment of Efficacy | Patient | Very Good | 22 Participants |
| Metronidazole | Subjective Assessment of Efficacy | Patient | Good | 24 Participants |
| Metronidazole | Subjective Assessment of Efficacy | Investigator | Very Good | 49 Participants |
| Metronidazole | Subjective Assessment of Efficacy | Patient | Moderate | 8 Participants |
| Metronidazole | Subjective Assessment of Efficacy | Investigator | Moderate | 4 Participants |
Secondary
Subjective Assessment of Tolerability
Tolerability was assessed by patients as 'very good', 'good', 'moderate' or 'poor'.
Time frame: One week
Population: Many missing values
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dequalinium Chloride | Subjective Assessment of Tolerability | Very good | 30 Participants |
| Dequalinium Chloride | Subjective Assessment of Tolerability | Good | 17 Participants |
| Dequalinium Chloride | Subjective Assessment of Tolerability | Moderate | 3 Participants |
| Dequalinium Chloride | Subjective Assessment of Tolerability | Poor | 0 Participants |
| Metronidazole | Subjective Assessment of Tolerability | Poor | 3 Participants |
| Metronidazole | Subjective Assessment of Tolerability | Very good | 21 Participants |
| Metronidazole | Subjective Assessment of Tolerability | Moderate | 4 Participants |
| Metronidazole | Subjective Assessment of Tolerability | Good | 26 Participants |
Secondary
Therapeutic Cure
Combination of clinical and bacteriological cure
Time frame: One week & one month
Population: Some patients had a missing Nugent score
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dequalinium Chloride | Therapeutic Cure | Visit 1 (1 week) | 34 Participants |
| Dequalinium Chloride | Therapeutic Cure | Visit 2 (1 month) | 26 Participants |
| Metronidazole | Therapeutic Cure | Visit 1 (1 week) | 48 Participants |
| Metronidazole | Therapeutic Cure | Visit 2 (1 month) | 33 Participants |
Post Hoc
Patients Cured Based on Standard Amsel Criteria
Amsel criteria = presence of abnormal vaginal discharge, whiff test (fishy odor), clue cells, and pH \>4.5 Bacterial vaginosis = 3 or more Amsel criteria present Cure = absence of 2 or more Amsel criteria
Time frame: 1 week and 1 month
Population: Missing some outcome measures
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dequalinium Chloride | Patients Cured Based on Standard Amsel Criteria | One week | 68 Participants |
| Dequalinium Chloride | Patients Cured Based on Standard Amsel Criteria | One month | 61 Participants |
| Metronidazole | Patients Cured Based on Standard Amsel Criteria | One month | 67 Participants |
| Metronidazole | Patients Cured Based on Standard Amsel Criteria | One week | 73 Participants |