Boric Acid + Fluconazole for Vaginal Yeast Infections
(THRIVE-yeast Trial)
Recruiting in Palo Alto (17 mi)
Age: 18 - 65
Sex: Female
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase < 1
Recruiting
Sponsor: University of Manitoba
Disqualifiers: Pregnancy, Hysterectomy, BV infection, others
No Placebo Group
Approved in 5 Jurisdictions
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.
12345Is 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.
35678How 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.
2591011Eligibility 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
+1 more
Trial 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
Participant Groups
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.
3Treatment groups
Active Control
Group I: Recurrent Infection Cohort - symptomaticActive Control2 Interventions
Participants with a history of recurrent vulvovaginal candidiasis infections who have an active symptomatic infection when they come to clinic
Group II: Asymptomatic CohortActive Control1 Intervention
Participants with no history of vulvovaginal candidiasis
Group III: Recurrent Infection Cohort - asymptomaticActive Control1 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, Australia 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
🇦🇺 Approved in Australia as Diflucan for:
- Vulvovaginal candidiasis
- Oropharyngeal candidiasis
- Esophageal candidiasis
- Cryptococcal meningitis
- Candidemia
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Health Science Centre (HSC)Winnipeg, Canada
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Who Is Running the Clinical Trial?
University of ManitobaLead Sponsor
Research ManitobaCollaborator
Manitoba Medical Service FoundationCollaborator
References
Single-dose systemic oral fluconazole for the treatment of vaginal candidiasis. [2019]To evaluate the acceptance of fluconazole given in a single oral dose, for the safe, effective treatment of vaginal candidiasis.
Fluconazole-Resistant Candida albicans Vaginal Infections at a Referral Center and Treated With Boric Acid. [2023]The authors investigate the incidence of clinical and mycological resistance of Candida albicans vulvovaginitis (VVC) at the Jefferson Vulvovaginal Health Center. They also review their experience with boric acid in the treatment of fluconazole-resistant VVC.
Treatment of vaginal candidiasis with a single oral dose of fluconazole. Multicentre Study Group. [2019]A single dose of 150 mg fluconazole was used to treat 180 patients with clinical and mycological evidence of vaginal candidiasis in an open, non-comparative, multicentre trial. The clinical response to treatment was excellent, with 97% of patients cured or markedly improved after 5 to 16 days. At long-term assessment (27 to 62 days), the proportion cured was 88%. Candida was eradicated from the vagina in 93% of patients at short-term assessment and in 73% at long-term assessment. The rate of relapse, reinfection or recolonization at long-term assessment in patients who had responded at short-term assessment was 23%. The incidence of side-effects was low, and consisted mainly of mild gastrointestinal complaints. Abnormal laboratory test results occurred in 15 of 167 evaluable patients, but all were minor and of minimal clinical significance. Oral fluconazole given in a single dose of 150 mg is an effective, safe and well tolerated treatment for vaginal candidiasis.
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]A large proportion of vulvovaginal candidiasis (VVC) in diabetes is due to non-albicans Candida species such as C. glabrata and C. tropicalis. Observational studies indicate that diabetic patients with C. glabrata VVC respond poorly to azole drugs. We evaluated the response to oral fluconazole and boric acid vaginal suppositories in diabetic patients with VVC.
Prolonged (3-month) mycological cure rate after boric acid suppositories in diabetic women with vulvovaginal candidiasis. [2013]Patients with diabetes mellitus (DM) are at increased risk of vulvovaginal candidiasis (VVC) due to C. glabrata. In our previous study we had shown that patients with diabetes mellitus and VVC show an overall superior mycological cure rate (74% versus 51%) with boric acid therapy at 15th day as compared to fluconazole. Present study was carried out to assess long term response to boric acid in diabetic women with VVC.
Efficacy and safety of a single oral 150 mg dose of fluconazole for the treatment of vulvovaginal candidiasis in Japan. [2022]Vulvovaginal candidiasis is the second most common cause of vaginal infections following bacterial vaginosis. For the treatment of vulvovaginal candidiasis, antifungal agents are used either as topical (vaginal tablets and cream) or oral formulations. A single oral 150 mg dose of fluconazole has been recommended as the standard therapy for uncomplicated, acute vulvovaginal candidiasis in global guidelines; however, in Japan oral fluconazole therapy has not been approved. We conducted a phase 3 study to evaluate the efficacy and safety of a single oral 150 mg dose of fluconazole in Japanese subjects with vulvovaginal candidiasis for regulatory submission. A total of 157 subjects received a single oral 150 mg dose of fluconazole. Candida species (104 strains) were identified by fungal culture from 102 subjects at baseline, including Candida albicans (100 strains). The efficacy rate for the therapeutic outcome (assessed based on a comprehensive evaluation of the clinical and mycological efficacy in each subject) was 74.7% (74/99) on Day 28 in the modified Intent-To-Treat (m-ITT) population. Concerning the clinical and mycological efficacy on Day 28 in the m-ITT population, the cure, cure or improvement, and eradication rates were 81.6%, 95.9%, and 85.9%, respectively. The most common treatment-related adverse events were diarrhea and nausea (1.9% for each). No clinically significant safety issues were reported. A single oral 150 mg dose of fluconazole demonstrated excellent therapeutic efficacy and was well tolerated in Japanese subjects with vulvovaginal candidiasis.
Safety of fluconazole in the treatment of vaginal candidiasis. A prescription-event monitoring study, with special reference to the outcome of pregnancy. [2019]A prescription-event monitoring (PEM) study has confirmed that fluconazole, a bis-triazole oral antifungal drug, is a safe and effective treatment for vaginal candidiasis. Useful information was available on 15,015 questionnaires returned by general practitioners. The events were compared with those recorded in PEM studies of itraconazole and 31 other drugs in a total of more than 330,000 patients. The frequency of events in the study of itraconazole was almost identical. Upper respiratory tract and genito-urinary infections were reported with above-average frequency but the relationship was with the disease being treated rather than the drug itself. No serious adverse effects were recorded with an unacceptably high incidence. None of the 125 deaths was caused by fluconazole. Although contraindicated for vaginal candidiasis in pregnancy, fluconazole was taken by 289 women at some time during the months before or during pregnancy; a follow-up study by questionnaire of the outcome of pregnancy showed fluconazole to be without harmful effect. It is concluded that fluconazole is a well tolerated drug in the treatment of vaginal candidiasis and is associated with very few adverse effects.
Guideline: vulvovaginal candidosis (AWMF 015/072), S2k (excluding chronic mucocutaneous candidosis). [2015]The oestrogenised vagina is colonised by Candida species in at least 20% of women; in late pregnancy and in immunosuppressed patients, this increases to at least 30%. In most cases, Candida albicans is involved. Host factors, particularly local defence mechanisms, gene polymorphisms, allergies, serum glucose levels, antibiotics, psycho-social stress and oestrogens influence the risk of candidal vulvovaginitis. Non-albicans species, particularly Candida glabrata, and in rare cases also Saccharomyces cerevisiae, cause less than 10% of all cases of vulvovaginitis with some regional variation; these are generally associated with milder signs and symptoms than normally seen with a C. albicans-associated vaginitis. Typical symptoms include premenstrual itching, burning, redness and odourless discharge. Although itching and redness of the introitus and vagina are typical symptoms, only 35-40% of women reporting genital itching in fact suffer from vulvovaginal candidosis. Medical history, clinical examination and microscopic examination of vaginal content using 400× optical magnification, or preferably phase contrast microscopy, are essential for diagnosis. In clinically and microscopically unclear cases and in chronically recurring cases, a fungal culture for pathogen determination should be performed. In the event of non-C. albicans species, the minimum inhibitory concentration (MIC) should also be determined. Chronic mucocutaneous candidosis, a rarer disorder which can occur in both sexes, has other causes and requires different diagnostic and treatment measures. Treatment with all antimycotic agents on the market (polyenes such as nystatin; imidazoles such as clotrimazole; and many others including ciclopirox olamine) is easy to administer in acute cases and is successful in more than 80% of cases. All vaginal preparations of polyenes, imidazoles and ciclopirox olamine and oral triazoles (fluconazole, itraconazole) are equally effective (Table ); however, oral triazoles should not be administered during pregnancy according to the manufacturers. C. glabrata is not sufficiently sensitive to the usual dosages of antimycotic agents approved for gynaecological use. In other countries, vaginal suppositories of boric acid (600 mg, 1-2 times daily for 14 days) or flucytosine are recommended. Boric acid treatment is not allowed in Germany and flucytosine is not available. Eight hundred-milligram oral fluconazole per day for 2-3 weeks is therefore recommended in Germany. Due to the clinical persistence of C. glabrata despite treatment with high-dose fluconazole, oral posaconazole and, more recently, echinocandins such as micafungin are under discussion; echinocandins are very expensive, are not approved for this indication and are not supported by clinical evidence of their efficacy. In cases of vulvovaginal candidosis, resistance to C. albicans does not play a significant role in the use of polyenes or azoles. Candida krusei is resistant to the triazoles, fluconazole and itraconazole. For this reason, local imidazole, ciclopirox olamine or nystatin should be used. There are no studies to support this recommendation, however. Side effects, toxicity, embryotoxicity and allergies are not clinically significant. Vaginal treatment with clotrimazole in the first trimester of a pregnancy reduces the rate of premature births. Although it is not necessary to treat a vaginal colonisation of Candida in healthy women, vaginal administration of antimycotics is often recommended in the third trimester of pregnancy in Germany to reduce the rate of oral thrush and napkin dermatitis in healthy full-term newborns. Chronic recurrent vulvovaginal candidosis continues to be treated in intervals using suppressive therapy as long as immunological treatments are not available. The relapse rate associated with weekly or monthly oral fluconazole treatment over 6 months is approximately 50% after the conclusion of suppressive therapy according to current studies. Good results have been achieved with a fluconazole regimen using an initial 200 mg fluconazole per day on 3 days in the first week and a dosage-reduced maintenance therapy with 200 mg once a month for 1 year when the patient is free of symptoms and fungal infection (Table ). Future studies should include Candida autovaccination, antibodies to Candida virulence factors and other immunological experiments. Probiotics with appropriate lactobacillus strains should also be examined in future studies on the basis of encouraging initial results. Because of the high rate of false indications, OTC treatment (self-treatment by the patient) should be discouraged.
Treatment of vaginitis caused by Candida glabrata: use of topical boric acid and flucytosine. [2019]The purpose of this study was to review the treatment outcome and safety of topical therapy with boric acid and flucytosine in women with Candida glabrata vaginitis.
Treatment of vulvovaginal candidiasis with boric acid powder. [2019]A double-blind comparison was made of the use of 14 daily intravaginal gelatin capsules containing 600 mg of boric acid powder versus the use of identical capsules containing 100,000 U nystatin diluted to volume with cornstarch for the treatment of vulvovaginal candidiasis albicans. Cure rates for boric acid were 92% at 7 to 10 days after treatment and 72% at 30 days, whereas the nystatin cure rates were 64% at 7 to 10 days and 50% at 30 days. The speed of alleviation of signs and symptoms was similar for the two drugs. There were no untoward side effects, and cervical cytologic features were not affected. In vitro studies found boric acid to be fungistatic and its effectiveness to be unrelated to pH. Blood boron analyses indicated little absorption from the vagina and a half-life of less than 12 hours. Acceptance by the patients was better than for "messy" vaginal creams, and self-made capsules containing boric acid powder are inexpensive (31 cents for fourteen) compared with the costly medication commonly prescribed.
Efficacy of maintenance therapy with topical boric acid in comparison with oral itraconazole in the treatment of recurrent vulvovaginal candidiasis. [2013]Our purpose was to examine the efficacy of a topical long-term treatment with boric acid versus an oral long-term treatment (itraconazole) in the cure and prevention of recurrent vulvovaginal candidiasis.