Zinc-containing Vaginal Gel and Oral Fluconazole for Vulvovaginal Candidiasis.

Study Overview
=================
Brief Summary
-----------------
Vaginitis is one of the most common gynecological problems in women. Candida albicans is responsible for more than 85% of vaginal fungal infections and reinfection after standard treatment is quite common. The aim of this study is to compare the effects of a zinc-containing vaginal gel and oral fluconazole on the treatment and recurrence of vulvovaginal candidiasis (VVC). The investigator's hypothesis is that zinc-containing vaginal gel may decrease the rate of reinfection after standard treatment with oral 150 mg fluconazole.

Detailed Description
-----------------
Randomized controlled trial will be conducted on 76 women with VVC, as confirmed by clinical and laboratory diagnosis. The participants will be allocated into two groups using blocked randomization method. In the control group participants will receive oral fluconazole treatment with a single dose of oral fluconazole (150 mg) while in the treatment group women will receive a single oral dose of fluconazole (150mg) followed by treatment with a zinc-containing vaginal gel (daily for 2 weeks and twice per week thereafter). Vaginal samples will be collected (vaginal swab and cervicovaginal lavage) at baseline and 4-8-12 weeks after starting treatment. In addition, the clinical signs and symptoms will be assessed before the intervention and follow-ups. Women will be asked to report any new symptoms of vaginal infections and will be asked to return for in-office evaluation.

Official Title
-----------------
Randomized Controlled Trial to Assess the Effectiveness of a Zinc-containing Vaginal Gel and Fluconazole on Treatment and Recurrence of Vulvovaginal Candidiasis.

Conditions
-----------------
Vulvovaginal Candidiasis, Vaginal Yeast Infections

Intervention / Treatment
-----------------
* Drug: JUVIA zinc containing vaginal gel treatment
* Drug: Fluconazole 150Mg Tab


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy, nonpregnant female participants aged ≥18 years with a clinical diagnosis of symptomatic acute VVC. Positive baseline potassium hydroxide (KOH) wet mount from a vaginal smear revealing filamentous hyphae/pseudohyphae or budding yeast cells. Presence of ≥1 vulvovaginal sign. Presence of ≥1 vulvovaginal symptom. Composite Candida severity score of ≥4. Exclusion Criteria: Abnormal Papanicolaou smear in the preceding 12 months. Patients who had oral or intravenous antifungal agents within 4 weeks, or used topical vaginal antifungal drugs within 1 week before the study. Known human immunodeficiency virus infection, Liver disease or abnormal liver function tests, lactation, pregnancy, and allergy to azole agents or zinc. Women with non-albicans Candida species will be excluded from the final data analysis.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: JUVIA zinc-containing vaginal gel and Fluconazole<br>JUVIA zinc containing vaginal gel group. Receive oral fluconazole treatment (150 mg) and after that participants will use a zinc containing- vaginal gel for 12 weeks. | Drug: JUVIA zinc containing vaginal gel treatment<br>* Women receive a single oral dose of fluconazole (150mg) followed by treatment with JUVIA zinc containing vaginal gel (daily for 2 weeks and twice per week thereafter).<br>Drug: Fluconazole 150Mg Tab<br>* Women receive oral fluconazole treatment with a single dose of oral fluconazole (150 mg).<br>|
| Active Comparator: Fluconazole<br>Control group. Receive oral fluconazole treatment. | Drug: Fluconazole 150Mg Tab<br>* Women receive oral fluconazole treatment with a single dose of oral fluconazole (150 mg).<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical cure | The proportion of participants with clinical cure throughout the study period. Clinical cure is defined as follows: complete resolution of signs and symptoms pertaining to VVC and no new sign or symptom of VVC during the follow-up period. | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to initial symptom resolution. |  | 12 weeks | 
| Vaginal fungal culture for Candida species. | Proportion of negative vaginal fungal culture for Candida species. | 12 weeks | 
| Clinical cure at days 28, 56, 84 | The proportion of participants with clinical cure at days 28, 56, 84. Clinical cure is defined as follows: complete resolution of signs and symptoms pertaining to VVC and no new sign or symptom of VVC during the follow-up period (at days 28, 56, 84). | 12 weeks | 
| Candida severity score | Minimum score: 0; maximum score: 18; higher score worse outcome. | 12 weeks | 
| PRA-1 level |  | 12 weeks | 
| CVL zinc level |  | 12 weeks | 
| Vaginal pH |  | 12 weeks | 
| Vaginal neutrophil count |  | 12 weeks | 
| Concentration of calprotectin, IL-1beta, IL-8 in the vaginal sample by ELISA |  | 12 weeks | 
| Vaginal measurement of CEF1, ACT1, PRA1, ECE1, HWP1, SAP6 expression by qRT-PCR |  | 12 weeks | 
| Vulvovaginal symptoms questionnaire | Minimum score: 0; maximum score: 21; higher scores indicates worse symptoms | 12 weeks | 
| Vaginal Health Index | Minimum score: 5; maximum score: 25; lower scores indicates worse symptoms | 12 weeks | 
| Reported Adverse Events (AEs) and Serious Adverse Events (SAEs) |  | 12 weeks |