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Topical Metronidazole and Miconazole Co-formulated Vaginal Suppositories for Preventing Vaginal Infections in HIV-seronegative Women

Primary Purpose

Bacterial Vaginosis, Candidiasis, Trichomoniasis

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Neo-Penotran® Forte (active ingredient Metronidazole & Miconazole Nitrate)
Placebo
Sponsored by
National Institute of Allergy and Infectious Diseases (NIAID)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Bacterial Vaginosis focused on measuring Bacterial vaginosis, metronidazole, miconazole, vulvovaginal candidiasis, trichomonas vaginalis, women, Kenya

Eligibility Criteria

18 Years - 45 Years (Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

  • Informed consent obtained and informed consent form (ICF) signed.
  • Female, aged 18-45 years.
  • Sexually active with greater than or equal to 4 episodes of sex with a male partner during the past month.
  • Human immunodeficiency virus (HIV)-seronegative on both HIV tests in parallel screening.

  • Presence of bacterial vaginosis (BV) and/or vulvovaginal candidiasis (VVC) and/or T. vaginalis infection at screening:

    1. BV: Microscopic criteria (Nugent's score greater than or equal to 7)
    2. VVC: Fungal elements (pseudohyphae, blastoconidia, or both) on vaginal saline wet mount plus a positive culture showing yeast on Sabouraud's agar.
    3. T. vaginalis infection: Identification of motile trichomonads on vaginal saline wet preparation.
  • Able and willing to comply with study visit schedule and procedures during the 12-month period of follow-up.
  • Able and willing to abstain from sex or to use non-latex condoms (provided) for 24 hours following insertion of each vaginal suppository.
  • Willing to abstain from alcohol during, and for 48 hours after, treatment.
  • Plan to remain in study area for the next year.
  • Agree to not participate in other research studies involving drugs, medical devices, or vaginal products for the duration of study.

Exclusion Criteria:

  • Currently pregnant (positive urine Beta-Human Chorionic Gonadotropin (hCG) or planning to conceive during the next 12 months (by self-report).
  • Currently breastfeeding.
  • Within first 3 months post-partum.
  • Current menstruation - women who are currently menstruating may be enrolled following the completion of menses.
  • History of 4 or more episodes of treatment for any vaginal infection in the past 12 months. This would be a cumulative total, including any treatment for bacterial vaginosis (BV) and/or vulvovaginal candidiasis (VVC) and/or Trichomonas vaginalis (TV) and/or syndromic.

  • History of medical condition that would contraindicate use of the study product

    1. Porphyria
    2. Epilepsy
    3. Serious liver disease or signs and symptoms consistent with serious liver disease including jaundice, ascites, esophageal varices, encephalopathy, and bleeding disorders.
    4. Renal failure
  • History of adverse reaction to the study medications (intravaginal metronidazole or miconazole).

  • Current use of medication that may interact with the study drug (due to vaginal absorption of study drug)

    1. Warfarin
    2. Phenytoin
    3. Phenobarbital
    4. Disulfiram
    5. Cimetidine
    6. Lithium
    7. Astemizole
    8. Terfenadine
  • Current use of oral or intravaginal antifungal medication.
  • Current use of oral or intravaginal metronidazole, tinidazole, or clindamycin.
  • Current use of latex diaphragm.
  • As determined by the investigator, a medical condition or situation exists such that study participation would not be advisable.

Sites / Locations

  • University of Alabama at Birmingham Medical Center
  • Women's Health Project - Ganjoni Municipal Clinic
  • University of Nairobi - Center for STD/HIV Research & Training
  • University of Nairobi - Kenya AIDS Vaccine Initiative

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Arm 1

Arm 2

Arm Description

Intravaginal metronidazole 750 mg plus miconazole 200 mg (co-formulated suppositories) nightly for 5 consecutive nights each month; 117 Subjects.

Placebo suppositories nightly for five consecutive nights each month; 117 Subjects.

Outcomes

Primary Outcome Measures

Efficacy of Monthly Periodic Presumptive Treatment (PPT) Using Metronidazole With Miconazole Intravaginal Suppositories Versus Matching Placebo Nightly for Five Nights Each Month for Preventing Vulvovaginal Candidiasis (VVC).
Percentage of follow-up visits (Months 2, 4, 6, 8, 10, 12) positive for VVC based on the presence of fungal elements (pseudohyphae, blastoconidia, or both) on vaginal saline wet mount plus a positive culture showing yeast on Sabouraud's agar.
Efficacy of Monthly Periodic Presumptive Treatment (PPT) Using Metronidazole With Miconazole Intravaginal Suppositories Versus Matching Placebo Nightly for Five Nights Each Month for Preventing Bacterial Vaginosis (BV).
Percentage of follow-up visits (Months 2, 4, 6, 8, 10, 12) positive for BV as determined by applying standard microscopic scoring criteria (Nugent's criteria) to vaginal Gram stained slides. BV is diagnosed when the score is greater than or equal to 7.

Secondary Outcome Measures

Efficacy of Monthly Periodic Presumptive Treatment (PPT) Using Metronidazole With Miconazole Intravaginal Suppositories Versus Placebo for Preventing Any Vaginal Infection (a Combined Endpoint Including BV, VVC, and Trichomonas Vaginalis Infection).
Percentage of follow-up visits (Months 2, 4, 6, 8, 10, 12) positive for any of three vaginal infections (BV, VVC, Trichomonas vaginalis infection).
Efficacy of Monthly Periodic Presumptive Treatment (PPT) Using Metronidazole With Miconazole Intravaginal Suppositories Versus Matching Placebo Nightly for Five Nights Each Month for Preventing BV by Clinical Criteria (Amsel's Criteria).
Percentage of follow-up visits (Months 2, 4, 6, 8, 10, 12) positive for BV by clinical criteria (Amsel's criteria).

Full Information

First Posted
October 28, 2010
Last Updated
September 26, 2014
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
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1. Study Identification

Unique Protocol Identification Number
NCT01230814
Brief Title
Topical Metronidazole and Miconazole Co-formulated Vaginal Suppositories for Preventing Vaginal Infections in HIV-seronegative Women
Official Title
A Double-Blind, Randomized Trial of Monthly Treatment With Topical Metronidazole and Miconazole Co-formulated Vaginal Suppositories Versus Placebo for Preventing Vaginal Infections in HIV-seronegative Women
Study Type
Interventional

2. Study Status

Record Verification Date
September 2014
Overall Recruitment Status
Completed
Study Start Date
April 2011 (undefined)
Primary Completion Date
August 2013 (Actual)
Study Completion Date
August 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)

4. Oversight

5. Study Description

Brief Summary
This research study is about vaginal infections such as bacterial vaginosis, yeast infections, and trichomoniasis. Usually, these infections can be treated with medication, but sometimes they come back after treatment. Researchers want to know if using vaginal suppositories can decrease the risk of vaginal infections. Participants will include 234 women who are sexually active (greater than or equal to 4 episodes of sex with men during the past month), HIV-negative, 18 to 45 years old, with bacterial infection [vaginosis and/or vulvovaginal candidiasis (VVC) and/or Trichomonas vaginalis] detected by laboratory testing at a screening visit. Women will receive vaginal suppositories containing drug or inactive ingredients (placebo). Participation in the study will be about 12 months. Study procedures include: urine and blood tests, physical exams, and questionnaires.
Detailed Description
Vaginal infections including bacterial vaginosis (BV), vulvovaginal candidiasis (VVC), and Trichomonas (T.) vaginalis are common and have been associated with increased risk of HIV and other sexually transmitted infections (STIs) in multiple prospective studies. Effective interventions for prevention of vaginal infections could substantially reduce the risk of HIV and other STIs in women. A recently completed trial has demonstrated that monthly periodic presumptive treatment (PPT) can reduce vaginal infections and promote Lactobacillus colonization. However, the oral regimen of metronidazole 2 grams plus fluconazole 150 mg was not sufficiently effective to warrant moving to Phase III HIV/STI prevention trials using this intervention. The identification of more efficacious regimens for reducing vaginal infections is a crucial step towards the development of inexpensive, female-controlled, non-coitally dependent HIV/STI risk reduction interventions for women. There is growing evidence that higher doses and longer courses may be more effective for treatment of vaginal infections than single-dose therapy. The overall goal of this protocol is to conduct a randomized, double-blind, placebo-controlled trial to test the efficacy of monthly PPT with topical metronidazole 750 mg plus miconazole 200 mg (co-formulated suppositories) versus matching placebo suppositories nightly for five nights each month for reducing the rates of BV and VVC among HIV-seronegative women. This regimen could produce sufficient reductions in vaginal infections to support its use in Phase III HIV and STI prevention trials. The study participants will include 234 women who are sexually active (greater than or equal to 4 episodes of heterosexual intercourse during the past month), HIV-seronegative, 18 to 45 years old, with BV and/or VVC and/or T. vaginalis detected by laboratory testing at a screening visit. There will be two study arms. The treatment arm (117 subjects) will receive PPT with intravaginal metronidazole 750 mg plus miconazole 200 mg (co-formulated suppositories) for five consecutive nights each month. The placebo arm (117 subjects) will receive PPT with identical placebo intravaginal suppositories for five consecutive nights each month. Individual participants will be in the study for one year.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Bacterial Vaginosis, Candidiasis, Trichomoniasis
Keywords
Bacterial vaginosis, metronidazole, miconazole, vulvovaginal candidiasis, trichomonas vaginalis, women, Kenya

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
234 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm 1
Arm Type
Experimental
Arm Description
Intravaginal metronidazole 750 mg plus miconazole 200 mg (co-formulated suppositories) nightly for 5 consecutive nights each month; 117 Subjects.
Arm Title
Arm 2
Arm Type
Placebo Comparator
Arm Description
Placebo suppositories nightly for five consecutive nights each month; 117 Subjects.
Intervention Type
Drug
Intervention Name(s)
Neo-Penotran® Forte (active ingredient Metronidazole & Miconazole Nitrate)
Intervention Description
Neo-Penotran® Forte (active ingredient Metronidazole & Miconazole Nitrate), co-formulated vaginal suppositories containing metronidazole 750 mg with miconazole 200 mg and excipients (Witepsol S 55). Witepsol S 55 is a hard fat suppository base. Such bases consist mainly of triglyceride esters of the higher saturated fatty acids along with varying proportions of mono- and diglycerides. 117 subjects receive nightly for 5 consecutive night each month.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo vaginal suppositories, identical in appearance to the active product; contains Witepsol S 55, Titanium Dioxide and D+C yellow #10 with no metronidazole or miconazole.117 subjects receive nightly for 5 consecutive nights each month.
Primary Outcome Measure Information:
Title
Efficacy of Monthly Periodic Presumptive Treatment (PPT) Using Metronidazole With Miconazole Intravaginal Suppositories Versus Matching Placebo Nightly for Five Nights Each Month for Preventing Vulvovaginal Candidiasis (VVC).
Description
Percentage of follow-up visits (Months 2, 4, 6, 8, 10, 12) positive for VVC based on the presence of fungal elements (pseudohyphae, blastoconidia, or both) on vaginal saline wet mount plus a positive culture showing yeast on Sabouraud's agar.
Time Frame
Months 2, 4, 6, 8, 10, and 12.
Title
Efficacy of Monthly Periodic Presumptive Treatment (PPT) Using Metronidazole With Miconazole Intravaginal Suppositories Versus Matching Placebo Nightly for Five Nights Each Month for Preventing Bacterial Vaginosis (BV).
Description
Percentage of follow-up visits (Months 2, 4, 6, 8, 10, 12) positive for BV as determined by applying standard microscopic scoring criteria (Nugent's criteria) to vaginal Gram stained slides. BV is diagnosed when the score is greater than or equal to 7.
Time Frame
Months 2, 4, 6, 8, 10, and 12.
Secondary Outcome Measure Information:
Title
Efficacy of Monthly Periodic Presumptive Treatment (PPT) Using Metronidazole With Miconazole Intravaginal Suppositories Versus Placebo for Preventing Any Vaginal Infection (a Combined Endpoint Including BV, VVC, and Trichomonas Vaginalis Infection).
Description
Percentage of follow-up visits (Months 2, 4, 6, 8, 10, 12) positive for any of three vaginal infections (BV, VVC, Trichomonas vaginalis infection).
Time Frame
Months 2, 4, 6, 8, 10, and 12.
Title
Efficacy of Monthly Periodic Presumptive Treatment (PPT) Using Metronidazole With Miconazole Intravaginal Suppositories Versus Matching Placebo Nightly for Five Nights Each Month for Preventing BV by Clinical Criteria (Amsel's Criteria).
Description
Percentage of follow-up visits (Months 2, 4, 6, 8, 10, 12) positive for BV by clinical criteria (Amsel's criteria).
Time Frame
Months 2, 4, 6, 8, 10, and 12.

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Informed consent obtained and informed consent form (ICF) signed. Female, aged 18-45 years. Sexually active with greater than or equal to 4 episodes of sex with a male partner during the past month. Human immunodeficiency virus (HIV)-seronegative on both HIV tests in parallel screening. Presence of bacterial vaginosis (BV) and/or vulvovaginal candidiasis (VVC) and/or T. vaginalis infection at screening: BV: Microscopic criteria (Nugent's score greater than or equal to 7) VVC: Fungal elements (pseudohyphae, blastoconidia, or both) on vaginal saline wet mount plus a positive culture showing yeast on Sabouraud's agar. T. vaginalis infection: Identification of motile trichomonads on vaginal saline wet preparation. Able and willing to comply with study visit schedule and procedures during the 12-month period of follow-up. Able and willing to abstain from sex or to use non-latex condoms (provided) for 24 hours following insertion of each vaginal suppository. Willing to abstain from alcohol during, and for 48 hours after, treatment. Plan to remain in study area for the next year. Agree to not participate in other research studies involving drugs, medical devices, or vaginal products for the duration of study. Exclusion Criteria: Currently pregnant (positive urine Beta-Human Chorionic Gonadotropin (hCG) or planning to conceive during the next 12 months (by self-report). Currently breastfeeding. Within first 3 months post-partum. Current menstruation - women who are currently menstruating may be enrolled following the completion of menses. History of 4 or more episodes of treatment for any vaginal infection in the past 12 months. This would be a cumulative total, including any treatment for bacterial vaginosis (BV) and/or vulvovaginal candidiasis (VVC) and/or Trichomonas vaginalis (TV) and/or syndromic. History of medical condition that would contraindicate use of the study product Porphyria Epilepsy Serious liver disease or signs and symptoms consistent with serious liver disease including jaundice, ascites, esophageal varices, encephalopathy, and bleeding disorders. Renal failure History of adverse reaction to the study medications (intravaginal metronidazole or miconazole). Current use of medication that may interact with the study drug (due to vaginal absorption of study drug) Warfarin Phenytoin Phenobarbital Disulfiram Cimetidine Lithium Astemizole Terfenadine Current use of oral or intravaginal antifungal medication. Current use of oral or intravaginal metronidazole, tinidazole, or clindamycin. Current use of latex diaphragm. As determined by the investigator, a medical condition or situation exists such that study participation would not be advisable.
Facility Information:
Facility Name
University of Alabama at Birmingham Medical Center
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294-0007
Country
United States
Facility Name
Women's Health Project - Ganjoni Municipal Clinic
City
Mombasa
State/Province
Coast
Country
Kenya
Facility Name
University of Nairobi - Center for STD/HIV Research & Training
City
Nairobi
Country
Kenya
Facility Name
University of Nairobi - Kenya AIDS Vaccine Initiative
City
Nairobi
Country
Kenya

12. IPD Sharing Statement

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Topical Metronidazole and Miconazole Co-formulated Vaginal Suppositories for Preventing Vaginal Infections in HIV-seronegative Women

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