BASIC (Boric Acid, Alternate Solution for Intravaginal Colonization) Study

Condition(s) targeted: Bacterial Vaginosis

Intervention: Gelatin (Drug); Boric acid (Drug); Metronidazole (Drug)

Phase: Phase 2/Phase 3

Status: Recruiting

Sponsored by: University of British Columbia

Official(s) and/or principal investigator(s):
Teresa Wood, MD, Principal Investigator, Affiliation: University of British Columbia
Konia Trouton, MD, Principal Investigator, Affiliation: University of Victoria
Melinda Zeron Mullins, Principal Investigator, Affiliation: University of Victoria

Overall contact:
Teresa Wood, MD, Phone: 250-388-2180, Email: onmybicycle@yahoo.com

Bacterial vaginosis (BV), the world's most common vaginal infection, continues to cost patients time, energy, comfort and money. BV is associated with increased incidence of sexually transmitted infections (including HIV), spontaneous abortion, pre-term labour, post-surgical infections, and endometritis. Current treatment for those women symptomatic for BV includes both oral and intravaginal antibiotics, such as metronidazole, which have success rates of 70-80 % at 1 month after treatment. These treatments also have high recurrence rates (49-66 % at one year after treatment) and side effects (10-20 % of women) that include secondary vaginal infection with candida. Intravaginal boric acid has been used for >100 years for the treatment of vaginal infections and is quite commonly prescribed today as a treatment for BV. It is cheap, easily accessible, easy to use, and is an effective treatment of other vaginal infections, such as candida. To date, there are no clinical trials studying the effectiveness of boric acid in the treatment of BV.

Objectives: To determine whether boric acid is at least as effective and as safe as metronidazole for treating women with symptomatic BV, our study will compare intravaginal boric acid to the current standard intravaginal treatment, metronidazole, and to a placebo. Our goal is to expand women's options for the treatment of BV. Hypothesis: Boric acid is an effective treatment of bacterial vaginosis as compared to placebo. Boric acid is at least as effective and as safe in the treatment of bacterial vaginosis as compared to metronidazole.

Official title: Back to BASICS: Boric Acid, Alternate Solution for Intravaginal Colonization, Comparing Intravaginal Metronidazole to Boric Acid in Women Symptomatic for Bacterial Vaginosis

Study design: Treatment, Randomized, Double Blind (Subject, Investigator), Placebo Control, Parallel Assignment, Safety/Efficacy Study

Primary outcome: Effectiveness of treatment of intravaginal boric acid and metronidazole at 1 week and 30 days post-treatment will be measured as absence of symptoms or negative vaginal swab (Nugent score less than 7) if symptoms are present for BV.

Secondary outcome: If during the 10 days of treatment of intravaginal boric acid and metronidazole the patient discontinues the treatment because of side effects or complained of intolerable side effects this will be considered a treatment failure for safety.

Detailed description: A minimum of 120 volunteer women will be recruited through participating family practice offices, gynecology offices, Victoria STI Clinic, Island Sexual Health Society Clinic, Vancouver Island Women's Clinic, student health clinics and youth clinics in Victoria, BC. Women with symptoms of BV, who also have a positive whiff test/pH test or subsequent positive vaginal swab for BV, will be asked to participate. Women will be included if they have both a positive test result for BV (whiff test/vaginal swab) and if they have any symptoms of BV present. The following criteria must be met for enrolment in the study: 1) ages 16-50 and pre-menopausal; 2) capable of giving written informed consent; 3) fluent comprehension of spoken and written English; 4) negative pregnancy test on enrolment day; 5) agree to follow study protocol; 6) documented BV infection by positive vaginal swab (minimum Nugent score of 7/10) +/- positive whiff test/pH >4. 5; 7) agree to no intercourse for the 10 days of treatment (or to use non-lubricated condoms if unavoidable); 8) agree not to douche or use any intravaginal products during treatment (including tampons, medications, devices); 9) abstain from alcohol during the 10 days of treatment (from 24 hours before through 72 hours after taking study medication); 10) agree to no new medications or antibiotics during treatment; 11) no current sexually transmitted infection as determined by history, physical exam and negative swabs for chlamydia, gonorrhea, candidiasis, trichomonas; 12) patient is reliable for follow up.

The following women would be excluded from study participation: 1) less than 16 or post-menopausal; 2) menstruating at diagnosis; 3) symptoms so severe as to make allocation to placebo unacceptable to the patient; 4) currently pregnant or at high risk for pregnancy; 5) current sexually transmitted infection (HIV, hepatitis, chlamydia, gonorrhea, trichomonas, HPV or HSV); 6) current yeast infection as determined by history, physical and swabs; 7) history of PID; 8) allergy to latex or metronidazole; 9) presently breast feeding; 10) any open wound, excoriation, vaginal irritation and including bartholin's cyst/abscess as determined by physical exam; 11) presence of another vulvar, vaginal or medical condition, including cervical neoplasia/treatment, that might confound treatment response; 12) using lithium, anti-coagulants or disulfiram drugs; 13) any antifungal or antibiotic use 14 days prior to enrolment 14) PAP smear done within one week of enrolment, 15) positive Whiff test, but negative vaginal swab result.

During the initial visit, the physician will take a history and do a speculum and manual pelvic exam for the woman. At the time of the pelvic exam the physician will ensure intact mucous membranes and anatomy, take swabs for chlamydia and gonorrhea, bacterial vaginosis, candidiasis, and trichomonas, and perform a whiff test using a provided, standardized 10% KOH potassium hydroxide solution. Vaginal discharge will also have pH testing done. If the whiff test is positive and the vaginal discharge pH is >4. 5, the woman will then take a urine pregnancy test, will be informed about the study, and will be given a handout explaining the study and the 3 possible treatment arms.

If the woman is interested in participating she will be given a "Study Intake Survey" to fill out, a consent form to sign, and an assigned number.

Within a few days, the physician would confirm participation, eligibility and exclusion criteria and collect the signed consent form. The patient will then be given a blinded, controlled and randomized treatment pack containing 10 capsules compounded and organized by a pharmacist. The patient will be given a package containing: 1) capsule applicators; 2) pads; 3) non-lubricated condoms; 4) a diary to record their daily use of the treatment, any problems or side effects, any symptom changes, or any problems with maintaining the study agreements; 5) information sheet outlining follow up instructions and emergency contact numbers to reach the study members. If the woman does not want to join the study the physician will prescribe a standard treatment of their choosing and would follow up as usual. If the whiff test is negative but the vaginal swab is found to be positive for bacterial vaginosis as per the Nugent score (score minimum of 7/10), the woman will be called back in to the office. If her symptoms are found to be persistant at this juncture, then she will be offered to enroll in the study or may elect to start a treatment of her physician's choosing. If the woman prefers to take some time to decide about the study, she will be given the information package, the survey form, and consent form to take home, as well as a prescription for the treatment of bacterial vaginosis. She can then return the next day with the forms filled out should she decide she would like to enroll in the study and be assigned a treatment arm. If she chooses not to enroll, she can fill the above-mentioned prescription and start the treatment for BV provided by her physician.

The women who satisfy the inclusion and exclusion criteria will be blindly and randomly assigned to one of 3 treatments (minimum of 40 women per treatment arm): 1) placebo (gelatin-filled size 0 gelatin capsules); 2) boric acid (600 mg boric acid in size 0 gelatin capsules); 3) metronidazole (37. 5 mg metronidazole in size 0 gelatin capsules). The treatments will be taken at night prior to sleep using the provided applicators for 10 days. The patient will be instructed to use a provided pads during the day and night for any discharge or fluid. The patient will record daily in a diary (provided) about compliance, side effects and problems, and changes in symptoms over the 10 days. The patient will be welcome to call the provided emergency numbers of the study members for any questions or problems related to the treatment. On day 5 of the treatment, the patient will receive a call or email from a study member to ask follow up questions about compliance, side effects, BV symptoms, and satisfaction of treatment.

On day 17-19 (one week after the treatment end), the patient will return to the clinic that enrolled her for reassessment and follow up pelvic exam and swabs. Noted are whether her BV symptoms are still present, and if she had any side effects or problems during treatment. If the vaginal swab is positive for BV found by Nugent score as a minimum of 7/10 +/- positive whiff test/pH >4. 5 and is symptomatic for BV then the physician will prescribe a standard medication of their choice. If the woman still has BV symptoms and a positive vaginal swab (Nugent score minimum of 7) for BV after the end of treatment, this will be considered a treatment failure addressing our primary endpoint: effectiveness at 7 days after treatment end. If the patient discontinued the treatment during the 10 days because of side effects or complained of intolerable side effects from the treatment this was considered a treatment failure referring to our secondary endpoint: safety.

On day 40-42 (one month after the treatment end) another follow up phone call and/or email will be made to the patient by a study member to ask whether symptoms of BV are present. If the symptoms are still present the patient will return to the clinic that enrolled her and is following her progress, for reassessment, follow up pelvic exam, swabs and treatment, as per physician's discretion. If the vaginal swab is positive for BV found by Nugent score as a minimum of 7/10 +/- positive whiff test/pH >4. 5 and the woman is symptomatic for BV, despite having negative results/symptoms for BV at day 17-19, this will be considered a treatment failure addressing our primary endpoint: effectiveness at 30 days after treatment end.

Minimum age: 16 Years. Maximum age: 50 Years. Gender(s): Female.

Criteria:

Inclusion Criteria:

Women will be included whether their complaint is symptoms of BV and have a positive whiff test/vaginal swab or if they have a positive whiff test/vaginal swab and are then asked if they have any symptoms of BV present. The following criteria must be met for enrolment in the study:

1. ages 16-50 and premenopausal;

2. capable of giving written informed consent;

3. English speaking;

4. negative pregnancy test on enrolment day;

5. agree to follow study protocol;

6. documented BV infection by positive vaginal swab +/- positive whiff test/pH > 4. 5;

7. agree to no intercourse for the 10 days of treatment (or to use non-lubricated condoms if unavoidable);

8. agree not to douche or use any intravaginal products during treatment (including tampons, medications, devices);

9. abstain from alcohol during the 10 days of treatment (from 24 hours before through 72 hours after taking study medication);

10. agree to no new medications or antibiotics during treatment;

11. no current sexually transmitted infection as determined by history, physical exam and negative swabs for chlamydia, gonorrhea, candidiasis, trichomonas;

12. patient is reliable for follow up.

Exclusion Criteria:

The following women would be excluded from study participation:

1. less than 16 or post-menopausal;

2. negative vaginal swab regardless of whiff test/pH > 4. 5;

3. menstruating at diagnosis;

4. symptoms so severe as to make allocation to placebo unacceptable to the patient;

5. currently pregnant or at high risk for pregnancy;

6. current sexually transmitted infection (HIV, hepatitis, chlamydia, gonorrhea, trichomonas, HPV or HSV);

7. current yeast infection as determined by history, physical and swabs;

8. history of PID;

9. allergy to latex or metronidazole;

10. presently lactating;

11. any open wound, excoriation, vaginal irritation and including bartholin's cyst/abscess as determined by physical exam;

12. presence of another vulvar, vaginal or medical condition, including cervical neoplasia treatment, that might confound treatment response;

13. using lithium, anti-coagulants or disulfiram drugs;

14. any antifungal or antibiotic use 14 days prior to enrolment

15. PAP smear done within one week of enrollment.

Teresa Wood, MD, Phone: 250-388-2180, Email: onmybicycle@yahoo.com

Multicentered (family practice offices, gyneological offices, STI Clinic, Sexual Health Clinic, and Youth Clinics in Victoria, BC), Victoria, British Columbia, Canada; Recruiting
Teresa Wood, MD, Phone: 250-388-2180, Email: onmybicycle@yahoo.com

Starting date: October 2008
Ending date: March 2011
Last updated: March 11, 2009