Bacterial Vaginosis
Conditions
Keywords
bacterial vaginosis, children, chlamydia, gonorrhea, mentronidazole, vaginal, women
Brief summary
The purpose of this study is to determine whether regular screening (every 2 months) and treatment for bacterial vaginosis (BV \[infection of the vagina\]) will reduce the number of incidences of chlamydia and gonorrhea (sexually transmitted diseases) over the course of a year. Chlamydial and gonococcal infections will be determined by vaginal swab testing at 4, 8, and 12 months after enrollment. Subjects will include 1500 women aged 15-25 years who have clinical evidence of BV, with no symptoms. Subjects will be randomly assigned to 1 of 2 possible study groups: the intervention group (treatment of BV) or the control group (no BV treatment). Every 2 months, subjects will complete a home self-testing kit for screening of BV using a swab. If BV is detected by self-test, the subjects in the interventional group will receive a 7 day course of the antibiotic metronidazole. Participants will be involved in study related procedures for up to 12 months.
Detailed description
Bacterial vaginosis (BV) is characterized by an imbalance in the normal vaginal bacterial flora. In the United States (US), BV is very common, and the most common cause of vaginitis, affecting approximately 1 in 10 sexually active young women. Because BV is so common, interventions targeting BV could have a tremendous public health impact. This is a phase III randomized controlled trial, in which the primary objective is to determine whether regular screening (every two months) and treatment for asymptomatic BV can reduce the one-year incidence of chlamydial and gonococcal infections, compared to a control group of women who receive regular monitoring (every two months) for BV but no treatment. The secondary study objective is to determine demographic and behavioral factors associated with the acquisition of BV, its persistence among women who are not treated for this condition, its spontaneous resolution, and its recurrence in women who are treated for this condition. This study protocol will enroll 1500 sexually active females, aged 15 - 25 years, from 6 US cities involved in the Sexually Transmitted Infections Clinical Trials Group network (Birmingham, Durham, Raleigh, Pittsburgh, Baltimore and San Francisco). To be eligible, women must have 2 or more risk factors for sexually transmitted diseases (STDs) and must have clinical evidence of asymptomatic BV at enrollment. For the purposes of this study, women with a vaginal pH\>4.5 with \>20 percent clue cells detected by microscopy to have asymptomatic BV. In addition, women must deny the presence of unusual or abnormal vaginal discharge or odor. Subjects will receive bi-monthly (every two months) home self-testing kits for BV using a vaginal swab. If BV is detected by self-test, the subjects in the intervention group will receive antibiotic treatment consisting of metronidazole 500mg twice daily for 7 days. Subjects will be randomized to either an intervention group (screening and treatment for BV) or a control group (monitoring for BV without treatment). Subjects in both the intervention group and the control group will complete bi-monthly (every 2 months) follow-up assessments for BV at months 2, 4, 6, 8, 10, and 12 (the final follow-up). In addition, subjects will provide sample collections for Chlamydia trachomatis and Neisseria gonorrhoeae at 4, 8, and 12 months after study entry.
Interventions
DRUGMetronidazole
Bi-monthly testing and treatment for BV with Metronidazole if BV is detected; 500mg twice daily for 7 days.
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Investigator)
Eligibility
Sex/Gender
FEMALE
Age
15 Years to 25 Years
Healthy volunteers
No
Inclusion criteria
-Subject provides written informed consent, or if subject is under age 18, parent signs informed consent and subject signs assent. -Female age 15-25 years (age at last birthday). -Vaginal intercourse within the past 3 months. -Asymptomatic bacterial vaginosis (BV) a. Vaginal pH \> 4.5 b. Clue cells on wet prep microscopy, \>20 percent c. Woman denies unusual or abnormal vaginal odor and discharge. -Two or more risk factors for sexually transmitted diseases (STDs): a. Age less than or equal to 20 b. African-American race c. Hispanic ethnicity d. Regular douching (at least one time per month) e. Two or more sex partners (past 12 months) f. Current or past STD (past 12 months). -Be able to understand study procedures . -Be able to comply with the study procedures for the entire length of the study.
Exclusion criteria
-Self-reported pregnancy, or no menstrual period in past 4 weeks and positive urine pregnancy test Note: We will exclude women who are pregnant at the time of enrollment because some guidelines recommend screening and treatment for bacterial vaginosis (BV) in high-risk women during pregnancy. -Regular use of antibiotics: use at least once daily for 2 of the past six months ( e.g., for acne). Note: Women taking antibiotics on a regular basis will be excluded because antibiotic use could affect both BV and chlamydia/gonorrhea infections. -Self-reported currently married/partnered and living with husband/partner of over 1 year. This does not include married women who are separated. Note: We will exclude women who are married and who are in established long term relationships because our goal is to enroll a sample of women at high-risk for sexually transmitted diseases (STDs). Although these women are at risk for STDs, they are at lower risk overall than women who are single, separated, or divorced. -Homeless Note: We will exclude women who are homeless because they are likely to be difficult to track. -Excessive alcohol use (consumes more than 14 alcoholic drinks per week, or is not willing to abstain from alcohol for one week in order to take medication). Note: We will exclude persons who do not think they could avoid drinking alcohol for one week to take an antibiotic (because metronidazole plus alcohol can lead to nausea and vomiting). -Allergy to metronidazole. -Current or history of seizure disorder. -Current or history of any kind of neuropathy. -Use of warfarin sodium (Coumadin ®). -Use of cimetidine (Tagamet ®). -Known liver disease. Note: we will exclude women with current seizure disorders, women taking warfarin (Coumadin), women taking cimetidine, and women with known liver disease; as such women may be at greater risk of adverse consequences from taking metronidazole. -History of hysterectomy. Note: we will exclude women who have had a hysterectomy because most chlamydial and gonococcal infections target the cervix. -Trichomonas vaginalis detected via wet mount during eligibility assessment. Note: we will also exclude women with a trichomonas infection identified during eligibility assessment through wet mount evaluation because we will treat them with a single dose of metronidazole. Such treatment would affect BV among women in the study. Women treated with metronidazole during eligibility assessment will have to wait for one month post treatment to become eligible for the study. -Unable to swallow pills. -Has an active uncontrolled medical condition, such as cancer, or per the judgment of the principal investigator should not participate in the study. -Women who are in the menstrual phase of the menstrual cycle. -Current participation in another research study of an investigational drug. -For women younger than age 18 years (19 in Alabama), a parent or guardian they live with is unaware that she is sexually active.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| One-year Incidence of Chlamydial and Gonococcal Infections in Women Who Receive Screening (Every 2 Months) and Treatment for Asymptomatic Bacterial Vaginosis as Compared to a Control Group With Regular Monitoring (Every 2 Months) But no Treatment | At 4, 8, and 12 months after enrollment. | Chlamydia and gonococcal infections were determined by vaginal swab testing collected at 4, 8, and 12 months after enrollment. Specimens were evaluated using the BD ProbeTec Amplified DNA AssayTM (Becton-Dickson, Inc. Sparks, MD). The primary outcome measure is the combined number of chlamydia and gonococcal infections. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Women Testing Positive for Bacterial Vaginosis (BV) Through 12 Months | 2, 4, 6, 8, 10, 12 months after enrollment | Percentage of women testing positive for BV at any follow-up visit. The outcome of BV status was determined by self-collected vaginal swab specimens that were evaluated by the Nugent criteria. A Nugent score of 7-10 indicates positive for BV. |
Countries
United States
Participant flow
Recruitment details
The target enrollment was 1370 and 1370 participants were randomized, but 5 participants were later found to be enrolled twice. The second enrollment of these participants were removed; therefore, the total enrolled was 1365.
Participants by arm
| Arm | Count |
|---|---|
| Control Bi-monthly testing for BV without treatment. | 682 |
| Intervention Metronidazole 500mg twice daily for 7 days for Bacterial Vaginosis (BV) detection
Metronidazole: Bi-monthly testing and treatment for BV with Metronidazole if BV is detected; 500mg twice daily for 7 days. | 683 |
| Total | 1,365 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Discontinued early | 24 | 17 |
| Overall Study | Lost to Follow-up | 176 | 155 |
Baseline characteristics
| Characteristic | Control | Total | Intervention |
|---|---|---|---|
| Age, Continuous | 21 years STANDARD_DEVIATION 2 | 21 years STANDARD_DEVIATION 2 | 21 years STANDARD_DEVIATION 2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 62 Participants | 122 Participants | 60 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 620 Participants | 1243 Participants | 623 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 4 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 11 Participants | 16 Participants | 5 Participants |
| Race (NIH/OMB) Black or African American | 535 Participants | 1065 Participants | 530 Participants |
| Race (NIH/OMB) More than one race | 54 Participants | 102 Participants | 48 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 9 Participants | 13 Participants | 4 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 26 Participants | 55 Participants | 29 Participants |
| Race (NIH/OMB) White | 45 Participants | 110 Participants | 65 Participants |
| Region of Enrollment United States | 682 participants | 1365 participants | 683 participants |
| Sex: Female, Male Female | 682 Participants | 1365 Participants | 683 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 682 | 0 / 683 |
| serious Total, serious adverse events | 3 / 682 | 7 / 683 |
Outcome results
Primary
One-year Incidence of Chlamydial and Gonococcal Infections in Women Who Receive Screening (Every 2 Months) and Treatment for Asymptomatic Bacterial Vaginosis as Compared to a Control Group With Regular Monitoring (Every 2 Months) But no Treatment
Chlamydia and gonococcal infections were determined by vaginal swab testing collected at 4, 8, and 12 months after enrollment. Specimens were evaluated using the BD ProbeTec Amplified DNA AssayTM (Becton-Dickson, Inc. Sparks, MD). The primary outcome measure is the combined number of chlamydia and gonococcal infections.
Time frame: At 4, 8, and 12 months after enrollment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Control | One-year Incidence of Chlamydial and Gonococcal Infections in Women Who Receive Screening (Every 2 Months) and Treatment for Asymptomatic Bacterial Vaginosis as Compared to a Control Group With Regular Monitoring (Every 2 Months) But no Treatment | 19.2 Number infections per 100 person-years |
| Intervention | One-year Incidence of Chlamydial and Gonococcal Infections in Women Who Receive Screening (Every 2 Months) and Treatment for Asymptomatic Bacterial Vaginosis as Compared to a Control Group With Regular Monitoring (Every 2 Months) But no Treatment | 18.3 Number infections per 100 person-years |
p-value: 0.75495% CI: [-12, 10.1]Two-sample test, Poisson
Secondary
Percentage of Women Testing Positive for Bacterial Vaginosis (BV) Through 12 Months
Percentage of women testing positive for BV at any follow-up visit. The outcome of BV status was determined by self-collected vaginal swab specimens that were evaluated by the Nugent criteria. A Nugent score of 7-10 indicates positive for BV.
Time frame: 2, 4, 6, 8, 10, 12 months after enrollment
Population: All randomized participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Control | Percentage of Women Testing Positive for Bacterial Vaginosis (BV) Through 12 Months | 92.5 percentage of participants |
| Intervention | Percentage of Women Testing Positive for Bacterial Vaginosis (BV) Through 12 Months | 82.6 percentage of participants |
p-value: <0.001Fisher Exact