Boric Acid + Fluconazole for Vaginal Yeast Infections

(THRIVE-yeast Trial)

Overseen By Vanessa HSC Women's Health Research Program, MD

Age: 18 - 65

Sex: Female

Trial Phase: Phase < 1

Sponsor: University of Manitoba

Disqualifiers: Pregnancy, Hysterectomy, BV infection, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 0

Duration: 4 weeks

105 Participants Needed

Trial Summary

What is the purpose of this trial?

Vulvovaginal candidiasis (VVC; colloquially referred to as a 'yeast infection') is a prevalent mucosal infection caused by Candida spp. that affects \~75% of women at least once in their life. VVC usually responds well to treatment, yet a small but significant fraction of women experience recurrent yeast infections even with weekly treatment. A further complication in understanding the causes of recurrent infections is that approximately one in five females have vaginal yeast present without any symptoms at any given point. The link between fungi, other microbes in the vagina ("microbiome"), and the human immune system remain poorly understood in the switch from having yeast present in the vagina without any symptoms and symptomatic yeast infections. Fungi also compose a normal component of the microbiome at other sites in the body (e.g., oral, skin, gastrointestinal tract, rectum) where they may serve as a source of re-infection following treatment. In addition to the commonly prescribed 'first choice' antifungal drug fluconazole, a second-line treatment, boric acid, has shown promise in the literature and has been used locally with success at increasing the time between recurrent infections. A drawback of this therapy, however, is cost, as it is a compounded medication, and patients have to pay out of pocket. The purpose of this study is to understand how the yeast and bacterial microbial communities differ for females with recurrent infections from females with their first yeast infection and females with vaginal yeast present without any symptoms, and to track yeast diversity following treatment with either boric acid or fluconazole. The investigators hypothesize that they will identify multiple subpopulations of yeast at multiple anatomical body sites in females with VVC and recurrent VVC. They anticipate finding evidence for recurrent infection from secondary sites by linking genomic diversity of vaginal yeast strains during symptomatic infection to strains from other body sites. They hypothesize that yeast isolated from females with recurrent infections will exhibit different drug response phenotypes than yeast from females with asymptomatic vaginal yeast. They hypothesize that the vaginal microbiome of post-treatment patients treated with boric acid will differ from that of fluconazole. Combined, they hypothesize that post-treatment response will differ between the drugs, indicating that treatment specifics influence the vaginal environment.

Do I need to stop my current medications for this trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment Boric Acid + Fluconazole for vaginal yeast infections?

Research shows that a single dose of 150 mg fluconazole is effective for treating vaginal yeast infections, with 97% of patients showing improvement shortly after treatment. Additionally, boric acid has been effective in treating fluconazole-resistant infections, especially in diabetic patients, with a higher cure rate compared to fluconazole alone. ^{1 2 3 4 5}

Is the combination of boric acid and fluconazole safe for treating vaginal yeast infections?

Fluconazole, taken as a single 150 mg oral dose, is generally safe and well-tolerated for treating vaginal yeast infections, with mild side effects like nausea and diarrhea reported in a small number of cases. Boric acid suppositories have shown good results in treating yeast infections, especially in diabetic women, but specific safety data for the combination of boric acid and fluconazole is not provided in the available research. ^{3 5 6 7 8}

How is the drug Boric Acid + Fluconazole unique for treating vaginal yeast infections?

This treatment combines boric acid, which is effective against fluconazole-resistant yeast infections, with fluconazole, a common oral antifungal, offering a potentially more effective solution for difficult-to-treat cases. ^{2 5 9 10 11}

Research Team

Aleeza Gerstein, PhD

Principal Investigator

University of Manitoba

Eligibility Criteria

This trial is for Canadian females aged 18-50 who have a yeast infection, also known as vulvovaginal candidiasis. It's not open to those who are pregnant, trying to conceive, or have had a hysterectomy.

Inclusion Criteria

I am a woman aged between 18 and 50.

Exclusion Criteria

I have had my uterus removed.

Currently pregnant

Trying to get pregnant

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive treatment with either fluconazole or boric acid to track yeast diversity and microbial community differences

4 weeks

Follow-up

Participants are monitored for changes in fungal and bacterial diversity, and host functional changes post-treatment

4 weeks

Treatment Details

Interventions

• Boric Acid Supp,Vag
• Fluconazole 150 mg

Trial Overview The study compares the effectiveness of boric acid suppositories and fluconazole (a common antifungal medication) in treating yeast infections and preventing recurrence by examining changes in vaginal microbial communities.

Participant Groups

Group I: Recurrent Infection Cohort - symptomatic Active Control 2 Interventions

Participants with a history of recurrent vulvovaginal candidiasis infections who have an active symptomatic infection when they come to clinic

Group II: Asymptomatic Cohort Active Control 1 Intervention

Participants with no history of vulvovaginal candidiasis

Group III: Recurrent Infection Cohort - asymptomatic Active Control 1 Intervention

Participants with a history of recurrent vulvovaginal candidiasis infections who do not have an active symptomatic infection when they come to clinic

Fluconazole 150 mg is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Diflucan for:

• Vulvovaginal candidiasis
• Oropharyngeal candidiasis
• Esophageal candidiasis
• Cryptococcal meningitis
• Candidemia

Approved in United States as Diflucan for:

• Vulvovaginal candidiasis
• Oropharyngeal candidiasis
• Esophageal candidiasis
• Cryptococcal meningitis
• Candidemia

Approved in Canada as Diflucan for:

• Vulvovaginal candidiasis
• Oropharyngeal candidiasis
• Esophageal candidiasis
• Cryptococcal meningitis
• Candidemia

Approved in Japan as Diflucan for:

• Vulvovaginal candidiasis
• Oropharyngeal candidiasis
• Esophageal candidiasis
• Cryptococcal meningitis
• Candidemia

Who Is Running the Clinical Trial?

University of Manitoba

Lead Sponsor

Trials

628

Recruited

209,000+

Research Manitoba

Collaborator

Trials

13

Recruited

17,500+

Manitoba Medical Service Foundation

Collaborator

Trials

19

Recruited

1,100+

Findings from Research

In a study involving 428 patients with vaginal candidiasis, fluconazole was found to be effective in relieving symptoms, with 72% of physicians and 69% of patients reporting positive outcomes.

The majority of patients (83.5%) preferred fluconazole over other treatments they had previously received, and there were no recurrences of the infection noted at the 6-week follow-up, indicating its safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-dose systemic oral fluconazole for the treatment of vaginal candidiasis. Kaplan, B., Rabinerson, D., Gibor, Y.[2019]

In a study of 970 patients with vaginal C. albicans infections, 7.3% were found to have clinically defined fluconazole-resistant infections, highlighting the prevalence of resistance in this population.

Treatment with vaginal boric acid was effective, achieving a mycological cure rate of 85.7% and a clinical cure rate of 73.7%, but there was a 14.3% recurrence rate within 3 months after treatment, indicating the need for ongoing management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fluconazole-Resistant Candida albicans Vaginal Infections at a Referral Center and Treated With Boric Acid. File, B., Sobel, R., Becker, M., et al.[2023]

A single 150 mg dose of fluconazole effectively treated vaginal candidiasis in 180 patients, with 97% showing improvement within 5 to 16 days and 88% remaining cured at long-term follow-up (27 to 62 days).

The treatment was well tolerated, with low side effects primarily limited to mild gastrointestinal issues, and only minor abnormal lab results observed in 15 patients, indicating fluconazole's safety as a treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of vaginal candidiasis with a single oral dose of fluconazole. Multicentre Study Group. [2019]

In a study of 112 diabetic patients with vulvovaginal candidiasis (VVC), those treated with boric acid vaginal suppositories showed a significantly higher mycological cure rate for C. glabrata infections compared to those treated with a single dose of oral fluconazole (63.6% vs. 28.6%).

The results suggest that boric acid is a more effective treatment option for diabetic women with C. glabrata VVC, highlighting the need for alternative therapies when azole drugs are less effective.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevalence of Candida glabrata and its response to boric acid vaginal suppositories in comparison with oral fluconazole in patients with diabetes and vulvovaginal candidiasis. Ray, D., Goswami, R., Banerjee, U., et al.[2013]

In a study of 40 diabetic women with vulvovaginal candidiasis (VVC), both boric acid and fluconazole showed similar long-term mycological cure rates at 3 months, with 71.4% and 63.1% remaining cured, respectively.

Despite a higher initial cure rate with boric acid (74% at 15 days), only about 46.6% of women remained cured at 3 months, indicating a need for further research into more effective long-term treatments for VVC in diabetic patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prolonged (3-month) mycological cure rate after boric acid suppositories in diabetic women with vulvovaginal candidiasis. Ray, D., Goswami, R., Dadhwal, V., et al.[2013]

In a phase 3 study involving 157 Japanese subjects, a single oral dose of 150 mg fluconazole showed a therapeutic efficacy rate of 74.7% for treating vulvovaginal candidiasis by Day 28, indicating it is an effective treatment option.

Fluconazole was well tolerated, with only mild treatment-related side effects like diarrhea and nausea reported in 1.9% of participants, and no significant safety concerns were identified.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of a single oral 150 mg dose of fluconazole for the treatment of vulvovaginal candidiasis in Japan. Mikamo, H., Matsumizu, M., Nakazuru, Y., et al.[2022]

A large prescription-event monitoring study involving 15,015 questionnaires confirmed that fluconazole is a safe and effective treatment for vaginal candidiasis, with no serious adverse effects reported.

Fluconazole was found to be well tolerated, even in women who took it before or during pregnancy, showing no harmful effects on pregnancy outcomes despite being contraindicated for use in pregnant women.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of fluconazole in the treatment of vaginal candidiasis. A prescription-event monitoring study, with special reference to the outcome of pregnancy. Inman, W., Pearce, G., Wilton, L.[2019]

Candida species, particularly Candida albicans, are commonly found in the vagina of women, with prevalence increasing during late pregnancy and in immunosuppressed individuals, highlighting the importance of understanding host factors that influence the risk of vulvovaginal candidosis.

Treatment with antifungal agents is generally effective in over 80% of cases, but specific strains like Candida glabrata may require higher doses or alternative treatments, and self-treatment is discouraged due to the high rate of misdiagnosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Guideline: vulvovaginal candidosis (AWMF 015/072), S2k (excluding chronic mucocutaneous candidosis). Mendling, W., Brasch, J., Cornely, OA., et al.[2015]

Topical boric acid treatment (600 mg daily for 2 to 3 weeks) was effective in achieving clinical success in 64% of women in Detroit and 71% in Beer Sheba with Candida glabrata vaginitis, indicating its efficacy as a treatment option.

Topical flucytosine cream showed a high success rate of 90% in women whose vaginitis did not respond to previous treatments, suggesting it is a valuable alternative for azole-refractory cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of vaginitis caused by Candida glabrata: use of topical boric acid and flucytosine. Sobel, JD., Chaim, W., Nagappan, V., et al.[2019]

Boric acid capsules showed a high cure rate of 92% for vulvovaginal candidiasis at 7 to 10 days, significantly outperforming nystatin, which had a cure rate of 64% in the same timeframe.

Both treatments had similar speeds in alleviating symptoms, but boric acid was better accepted by patients and was more cost-effective, costing only 31 cents for fourteen capsules compared to more expensive medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of vulvovaginal candidiasis with boric acid powder. Van Slyke, KK., Michel, VP., Rein, MF.[2019]

In a study of 22 women with recurrent vulvovaginal candidiasis, both boric acid and itraconazole treatments showed similar effectiveness in curing the infection during the treatment period, with no significant differences in culture results or symptoms.

However, after stopping treatment, both groups experienced high relapse rates (54.5%), indicating that while boric acid is a promising option for treatment, its benefits do not persist after therapy ends.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of maintenance therapy with topical boric acid in comparison with oral itraconazole in the treatment of recurrent vulvovaginal candidiasis. Guaschino, S., De Seta, F., Sartore, A., et al.[2013]

References

1. United States pubmed.ncbi.nlm.nih.gov

Single-dose systemic oral fluconazole for the treatment of vaginal candidiasis. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Fluconazole-Resistant Candida albicans Vaginal Infections at a Referral Center and Treated With Boric Acid. [2023]

3. Germany pubmed.ncbi.nlm.nih.gov

Treatment of vaginal candidiasis with a single oral dose of fluconazole. Multicentre Study Group. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

Prevalence of Candida glabrata and its response to boric acid vaginal suppositories in comparison with oral fluconazole in patients with diabetes and vulvovaginal candidiasis. [2013]

5. England pubmed.ncbi.nlm.nih.gov

Prolonged (3-month) mycological cure rate after boric acid suppositories in diabetic women with vulvovaginal candidiasis. [2013]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Efficacy and safety of a single oral 150 mg dose of fluconazole for the treatment of vulvovaginal candidiasis in Japan. [2022]

7. Germany pubmed.ncbi.nlm.nih.gov

Safety of fluconazole in the treatment of vaginal candidiasis. A prescription-event monitoring study, with special reference to the outcome of pregnancy. [2019]

8. Germany pubmed.ncbi.nlm.nih.gov

Guideline: vulvovaginal candidosis (AWMF 015/072), S2k (excluding chronic mucocutaneous candidosis). [2015]

9. United States pubmed.ncbi.nlm.nih.gov

Treatment of vaginitis caused by Candida glabrata: use of topical boric acid and flucytosine. [2019]

10. United States pubmed.ncbi.nlm.nih.gov

Treatment of vulvovaginal candidiasis with boric acid powder. [2019]

11. United States pubmed.ncbi.nlm.nih.gov

Efficacy of maintenance therapy with topical boric acid in comparison with oral itraconazole in the treatment of recurrent vulvovaginal candidiasis. [2013]