Randomized Controlled Trial of Treatment of Male Partners of Women With BV

• Sponsor: University of Alabama at Birmingham (Other)
• Overall Status: Completed
• CT.gov ID: NCT02209519
• Collaborator: Wayne State University (Other)
• Enrollment: 214
• Location: 1
• Arms: 2
• Actual Duration (Months): 48.9
• Patients Per Site Per Month: 4.4

Study Details

Study Description

Brief Summary

Male partners of womoen with recurrent bacteria vaginosis are randomized to treatment with metronidazole or placebo to compare the rates of recurrent BV in the women

Condition or Disease	Intervention/Treatment	Phase
Recurrent Bacterial Vaginosis	Drug: Metronidazole (male partner); Other: Placeob (male partner)	Phase 3

Detailed Description

This study will be performed as a phase III randomized, double-blinded trial to evaluate the efficacy of 1) metronidazole 500 mg PO BID for 7 days versus 2) placebo capsules alone for treatment of the male sexual partner of women with recurrent BV. The primary outcome is the rates of recurrent BV between these two groups. Although this is a phase III study we will carefully monitor potential toxicity in the males since it is currently not standard of care to treat males for this indication.

Women with symptomatic BV defined by Amsel criteria 1 and no evidence of STD will be invited to participate. Inclusion criteria are that the woman be at least 18 years of age, heterosexual, have symptoms of vaginal odor and/or discharge, meet the modified clinical (Amsel) criteria for BV (all must have a vaginal pH of >4.5, a positive whiff test, and clue cells to be eligible), have an enrollment Nugent score of 7 or greater, and a history of 2 or more episodes of BV in the previous year. She must have a regular current sex partner who would be willing to participate. We will exclude women who have had recurrent BV for greater than 3 years as well as women who have failed previous treatment studies since it is likely that these women are having recurrent BV as a result of relapse of the BV biofilm as opposed to reinfection.

Follow-up visits will be conducted at day 21, 8 and 16 weeks. At each follow-up visit, a questionnaire will be administered, diary reviewed, pelvic examination conducted and specimens (Gram stain, Amsel criteria, G vaginalis culture and detection of novel organisms) obtained as done at the enrollment visit. Participants will be asked to return the medication packages, a standard way of assessing adherence to the regimen. Cure will be ascertained using the clinical criteria for BV of Amsel 1 as well as the Nugent scoring system 16. The persistence or disappearance of specific organisms will be analyzed in relationship to these standard definitions of cure. Women who fail initial therapy or have recurrence of symptomatic BV during the course of the study will be re-treated with 7 days of metronidazole and dropped from the study at that time. Any woman found to have a positive screening test for gonorrhea or chlamydia will be treated appropriately and instructed to notify her partner of the need to be treated. Women with intercurrent vaginal yeast infections, which may occur, will be treated with oral fluconazole and continued in the study. Women with a positive culture for trichomonas will be dropped from the study as their male partners will require treatment with metronidazole.

Male Study Procedures

Males referred by their female sexual partner will be seen within 48 hours of enrollment of the female. Males will be consented and asked behavioral and historical questions using a gender appropriate questionnaire, with special emphasis on number of current sexual partners. A couple verification screening tool will be utilized to be certain they are current sexual partners48. The confidentiality of their answers will be emphasized. They will be examined and a urethral swab specimen obtained to be used for G vaginalis culture and then archived. Following the swabs, two external swabs from the coronal sulcus and a 10 ml first void urine specimen will be obtained. These specimens will also be used for G vaginalis culture and archived for possible use in detection of novel organisms. The urine will also be used for NAATS for N gonorrhoeae and C trachomatis and for the determining the presence or absence of

Gardnerella biofilm24. They will then be randomized to one of two treatment arms:

1. Metronidazole 500 mg PO twice a day for 7 days .

2. Placebo capsules PO twice a day for 7 days.

Both arms will also contain an instruction sheet on metronidazole.

Study Design

• Study Type: Interventional
• Actual Enrollment: 214 participants
• Allocation: Randomized
• Intervention Model: Single Group Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Randomized Controlled Trial of Treatment of Male Partners of Women With BV
• Actual Study Start Date: Feb 1, 2015
• Actual Primary Completion Date: Mar 1, 2019
• Actual Study Completion Date: Mar 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Metronidazole Male Partner: metronidazole 500 mg PO BID x 7days Female Partner: metronidazole 500 mg PO BID x 7days	Drug: Metronidazole (male partner); 500 mg PO BID for 7 days
Placebo Comparator: Placebo Male Partner: one tablet PO BID for 7 days Female Partner: metronidazole 500 mg PO BID x 7days	Other: Placeob (male partner); matching placebo capsules PO BID for 7 days

Outcome Measures

Primary Outcome Measures

1. Number of Female Partners Whose Male Partners Received Metronidazole Versus Females Whose Male Partners Did Not Receive Metrodiazole With Recurrence of BV in the Female [16 weeks post start of receipt of study drug]

   the female partners will be assessed for recurrence/persistence of BV. tRecurrence/persistence is measured by - Positive 3 - 4 Amsel criteria (vaginal pH > 4.7, clue cells, positive whiff test, homogenous discharge); Nugent score >3 No Recurrence/Persistence is measured by: - Presence of 0 -2 Amsel criteria; Nugent score 0-3.

Secondary Outcome Measures

1. Time to Recurrence of BV in Women Whose Partner Received Metronidazole Versus Females Whose Partners Did Not Receive Metronidazole [from the end of week 1 up to 16 weeks]

   time to recurrence measured in days

Eligibility Criteria

Criteria

• Ages Eligible for Study: 19 Years to 50 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria: Female

1. At least 18 years of age (19 years of age in Alabama due to State law)

2. Sexual partner to a female who meets study eligibility

3. Willingness to provide informed consent

4. Willingness to abstain from sexual intercourse or use condoms

5. Willingness to abstain from alcohol for the first week of the study

Inclusion Criteria: Male

1. At least 18 years of age (19 years of age in Alabama due to State law)

2. Heterosexual with a regular partner

3. History of 2 or more episodes of BV in the previous 12 months

4. Symptoms of BV including vaginal discharge and/or odor

5. Positive Amsel criteria for BV including vaginal pH >4.5, positive whiff test, presence of clue cells

6. Willingness to provide informed consent

7. Willingness to abstain from sexual intercourse or use condoms

8. Willingness to abstain from alcohol for the first week of the study

Exclusion criteria (both genders)

1. Allergy to metronidazole

2. Failure of the male partner to keep his appointment to be seen within 48 hours

3. Pregnant or breast feeding (females)

4. HIV or other chronic disease which in the opinion of the investigator would interfere with the ability to participate in this study

5. Subject requires concurrent lithium, coumadin, dilantin, or antabuse

6. Presence of trichomonas on wet prep of vaginal fluid (females)

7. Women with a history of recurrent BV for >3 years or women who have failed previous treatment studies for BV

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Jane Schwebke	Pell City	Alabama	United States	35128

Sponsors and Collaborators

• University of Alabama at Birmingham
• Wayne State University

Investigators

• Principal Investigator: jane Schwebke, MD, University of Alabama at Birmingham

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Feb 26, 2020

More Information

Publications

None provided.

• Responsible Party: Jane Schwebke, Principal Investigator, University of Alabama at Birmingham
• ClinicalTrials.gov Identifier: NCT02209519
• Other Study ID Numbers: 001
• First Posted: Aug 6, 2014
• Last Update Posted: Apr 27, 2020
• Last Verified: Apr 1, 2020

• Keywords provided by Jane Schwebke, Principal Investigator, University of Alabama at Birmingham: bacterial vaginosis; recurrence; male partner
• Additional relevant MeSH terms: Vaginosis, Bacterial; Vaginal Diseases; Metronidazole

Study Results

Participant Flow

Arm/Group Title	Metronidazole	Placebo
Arm/Group Description	Male Partner: metronidazole 500 mg PO BID x 7days Female Partner: metronidazole 500 mg PO BID x 7days Metronidazole (male partner): 500 mg PO BID for 7 days	Male Partner: one tablet PO BID for 7 days Female Partner: metronidazole 500 mg PO BID x 7days Placebo (male partner): matching placebo capsules PO BID for 7 days
Period Title: Overall Study
STARTED	107	107
COMPLETED	107	107
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Metronidazole	Placebo	Total
Arm/Group Description	Male Partner: metronidazole 500 mg PO BID x 7days Female Partner: metronidazole 500 mg PO BID x 7days Metronidazole (male partner): 500 mg PO BID for 7 days	Male Partner: one tablet PO BID for 7 days Female Partner: metronidazole 500 mg PO BID x 7days Placebo (male partner): matching placebo capsules PO BID for 7 days	Total of all reporting groups
Overall Participants	107	107	214
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	31.5 (6.9)	32.8 (8.1)	32.1 (7.5)
Sex: Female, Male (Count of Participants)
Female	107 100%	107 100%	214 100%
Male	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Count of Participants)
white	14 13.1%	15 14%	29 13.6%
african american	89 83.2%	88 82.2%	177 82.7%
multiracial	4 3.7%	4 3.7%	8 3.7%
hispanic	6 5.6%	4 3.7%	10 4.7%
non-hispanic	101 94.4%	103 96.3%	204 95.3%
Region of Enrollment (participants) [Number]
United States	107 100%	107 100%	214 100%

Outcome Measures

1. Primary Outcome

Title	Number of Female Partners Whose Male Partners Received Metronidazole Versus Females Whose Male Partners Did Not Receive Metrodiazole With Recurrence of BV in the Female
Description	the female partners will be assessed for recurrence/persistence of BV. tRecurrence/persistence is measured by - Positive 3 - 4 Amsel criteria (vaginal pH > 4.7, clue cells, positive whiff test, homogenous discharge); Nugent score >3 No Recurrence/Persistence is measured by: - Presence of 0 -2 Amsel criteria; Nugent score 0-3.
Time Frame	16 weeks post start of receipt of study drug

Outcome Measure Data

Analysis Population Description

those completing the study

Arm/Group Title	Metronidazole	Placebo
Arm/Group Description	Male Partner: metronidazole 500 mg PO BID x 7days Female Partner: metronidazole 500 mg PO BID x 7days Metronidazole (male partner): 500 mg PO BID for 7 days	Male Partner: one tablet PO BID for 7 days Female Partner: metronidazole 500 mg PO BID x 7days Placebo (male partner): matching placebo capsules PO BID for 7 days
Measure Participants	107	107
Count of Participants [Participants]	87 81.3%	86 80.4%

2. Secondary Outcome

Title	Time to Recurrence of BV in Women Whose Partner Received Metronidazole Versus Females Whose Partners Did Not Receive Metronidazole
Description	time to recurrence measured in days
Time Frame	from the end of week 1 up to 16 weeks

Outcome Measure Data

Analysis Population Description

unable to collect data due to lab issues

Arm/Group Title	Metronidazole	Placebo
Arm/Group Description	Male Partner: metronidazole 500 mg PO BID x 7days Female Partner: metronidazole 500 mg PO BID x 7days Metronidazole (male partner): 500 mg PO BID for 7 days	Male Partner: one tablet PO BID for 7 days Female Partner: metronidazole 500 mg PO BID x 7days Placeob (male partner): matching placebo capsules PO BID for 7 days
Measure Participants	0	0

Adverse Events

Time Frame	baseline through 16 weeks
Arm/Group Title	Metronidazole		Placebo
Arm/Group Description	Male Partner: metronidazole 500 mg PO BID x 7days Female Partner: metronidazole 500 mg PO BID x 7days Metronidazole (male partner): 500 mg PO BID for 7 days		Male Partner: one tablet PO BID for 7 days Female Partner: metronidazole 500 mg PO BID x 7days Placebo (male partner): matching placebo capsules PO BID for 7 days
All Cause Mortality
	Metronidazole		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/107 (0%)		0/107 (0%)
Serious Adverse Events
	Metronidazole		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/107 (0%)		1/107 (0.9%)
Musculoskeletal and connective tissue disorders
trauma	0/107 (0%)		1/107 (0.9%)
Other (Not Including Serious) Adverse Events
	Metronidazole		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	29/107 (27.1%)		31/107 (29%)
Gastrointestinal disorders
gastrointestinal	5/107 (4.7%)	5	5/107 (4.7%)	5
Infections and infestations
Infections and infestations	18/107 (16.8%)	18	21/107 (19.6%)	21
Injury, poisoning and procedural complications
Injury	0/107 (0%)	0	1/107 (0.9%)	1
Musculoskeletal and connective tissue disorders
musculoskelatal	1/107 (0.9%)	1	0/107 (0%)	0
Nervous system disorders
nervous	1/107 (0.9%)	1	3/107 (2.8%)	3
Psychiatric disorders
psychiatric	1/107 (0.9%)	1	0/107 (0%)	0
Reproductive system and breast disorders
reproductive system	1/107 (0.9%)	1	0/107 (0%)	0
Respiratory, thoracic and mediastinal disorders
respiratory	1/107 (0.9%)	1	1/107 (0.9%)	1
Skin and subcutaneous tissue disorders
skin	1/107 (0.9%)	1	0/107 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.