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Trial registered on ANZCTR


Registration number
ACTRN12618000219280
Ethics application status
Approved
Date submitted
5/02/2018
Date registered
9/02/2018
Date last updated
8/04/2020
Date data sharing statement initially provided
3/04/2019
Date results information initially provided
3/04/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Pilot study to determine the acceptability and tolerability of male partner treatment in women with bacterial vaginosis (BV) - stage 2
Scientific title
Combined oral and topical antimicrobial therapy for male partners of women with bacterial vaginosis: acceptability, tolerability and impact on the genital microbiota of couples - stage 2
Secondary ID [1] 293796 0
None
Universal Trial Number (UTN)
Trial acronym
Step Up
Linked study record
ACTRN12617001302347

Health condition
Health condition(s) or problem(s) studied:
Bacterial vaginosis 306202 0
Condition category
Condition code
Infection 305309 305309 0 0
Sexually transmitted infections
Renal and Urogenital 305310 305310 0 0
Other renal and urogenital disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
There are two treatment arms in this study:

Arm 1 (Dual-partner treatment): Women with BV receive standard treatment for their bacterial vaginosis (oral metronidazole 400 mg twice daily for seven days, or another first line treatment option if metronidazole was contraindicated or declined eg 2% vaginal clindamycin cream as one applicator vaginally for seven nights or a 5-day regimen of Metrogel). Male partners receive oral metronidazole 400mg twice daily and 2% clindamycin cream applied topically to the head of the penis and upper shaft (under the foreskin if uncircumcised) twice daily for seven days.

Arm 2 (Female only treatment): Women with BV receive standard treatment for their bacterial vaginosis (oral metronidazole 400 mg twice daily for seven days, or another first line treatment option if metronidazole was contraindicated or declined eg 2% vaginal clindamycin cream as one applicator vaginally for seven nights or a 5-day regimen of Metrogel). Male partners are untreated.

Adherence and side effects to treatment were self-reported by participants in a questionnaire on day 8 at the end of the treatment period.
Intervention code [1] 300050 0
Treatment: Drugs
Comparator / control treatment
The comparator is a female only treatment arm where the female receives standard treatment for her BV and her male partner does not receive treatment.
Control group
Active

Outcomes
Primary outcome [1] 304468 0
To determine the acceptability and tolerability of male partner treatment in women with BV. This is a composite primary outcome. Participants will self-report adherence to treatment and any side effects (e.g. nausea, headache, skin irritation, rash, vomiting) experienced at day 8. These data will be used as a measure of acceptability and tolerability of treatment.
Timepoint [1] 304468 0
Day 8 - at the end of treatment period
Secondary outcome [1] 342056 0
To determine if dual partner treatment (both the female and the male) for BV is associated with a sustained reduction in load of key BV-associated bacteria (BVAB) in the male and female genital tract over four months following treatment

The genital microbiota will be characterized using 16S rRNA gene sequencing. Changes in the composition of the genital microbiota will be assessed using Bray-Curtis scores. Changes in bacterial diversity (calculated using the Shannon diversity index) as well as changes in the abundance and prevalence of specific bacteria will be measured.
Timepoint [1] 342056 0
Baseline (day 0) and 3 months from baseline

Eligibility
Key inclusion criteria
Women will be eligible if they:
1. are 18-55 years of age
2. have symptomatic BV, microbiologically defined as a Nugent score of 4-10 and 3-4 Amsel criteria,
3. are willing and able to comply with protocol requirements
4. have a regular male partner who is willing to be enrolled in the trial
5. must have been in a relationship with their regular male partner for at least two months at the time of enrolment

Men will be eligible if:
1. their regular female partner meets the eligibility criteria
2. they are willing and able to comply with protocol requirements, which includes enrolling within a week of their partner
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Women will be ineligible if they:
1. are HIV positive
2. are pregnant or breast feeding
3. are diagnosed with current PID
4. have an allergy to both first line antibiotics for BV, metronidazole and clindamycin
5. test positive for C.trachomatis, N.gonorrhoeae or T.vaginalis at baseline
6. have other current sexual partners
7. are a current sex worker

Men will be ineligible if they:
1. report a drug allergy to metronidazole or clindamycin,
2. are HIV positive
3. have other current sexual partners
4. are a current sex worker

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Not applicable
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Not applicable
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Safety
Statistical methods / analysis
40 couples will be enrolled as a convenience sample to determine the acceptability and feasibility of male partner treatment.

Analyses will be undertaken to examine the influence of male partner treatment on BVAB on the penile skin and urethra at one week and to examine the influence of dual partner treatment on BVAB in the male and female genital tract over one month. For this analysis, mean differences in the abundance and prevalence of BVAB between pre-treatment (Day 0) and post-antibiotic (Day 8) samples will be compared in males using paired t-test or non-parametric equivalent. Mean differences in the abundance and prevalence of BVAB between endpoint (Month 3) and pre-treatment (Day 0) samples will also be compared in males and females using paired t-test or non-parametric equivalent. Ordination analysis will be used to investigate differences in the bacterial communities between the two treatment groups. These data will be used to inform sample size calculations for a RCT of male partner treatment.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 9798 0
The Alfred - Prahran
Recruitment postcode(s) [1] 18575 0
3053 - Carlton

Funding & Sponsors
Funding source category [1] 298412 0
Hospital
Name [1] 298412 0
Alfred Health
Address [1] 298412 0
55 Commercial Rd
Melbourne
VIC 3004
Country [1] 298412 0
Australia
Primary sponsor type
University
Name
Monash University
Address
Monash University
Wellington Road, Clayton
Victoria 3800
Country
Australia
Secondary sponsor category [1] 297549 0
None
Name [1] 297549 0
Address [1] 297549 0
Country [1] 297549 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 299409 0
Alfred Health Human Research Ethics Committee
Ethics committee address [1] 299409 0
The Alfred
Old Baker Building, Level 1,
55 Commercial Rd, Melbourne VIC 3004
Ethics committee country [1] 299409 0
Australia
Date submitted for ethics approval [1] 299409 0
06/12/2017
Approval date [1] 299409 0
09/12/2017
Ethics approval number [1] 299409 0
264/15

Summary
Brief summary
OVERALL AIM: This study aims to determine the feasibility and acceptability of treatment of male partners of women with bacterial vaginosis (BV).

OTHER AIMS: To examine the impact of dual partner treatment (male and female treatment) for BV on BV-associated bacteria on the male and female genitalia for 3 months after treatment.

BACKGROUND AND SIGNIFICANCE: BV is the most common cause of abnormal vaginal discharge in women of reproductive age affecting between 12-30% of women, suggesting it may currently affect at least 1 million Australian women. It can be associated with important complications such as miscarriage, premature birth, low birth weight, pelvic infection, and increased risk of HIV and sexually transmitted infections.

We have shown that BV recurrence (getting the infection back again) in women is common even after they have taken the recommended antibiotic treatment. A number of investigators have shown that BV-associated bacteria (BVAB) are present in male partners of women with BV on the penile skin and at the end of the urethra, but men have no symptoms of BV and male partner treatment is not currently recommended by current treatment guidelines. Studies of recurrent BV indicate that reinfection from sexual partners may be contributing to the high rates of recurrence but this requires more evaluation.

Metronidazole and topical clindamycin are both antibiotics approved for use in Australia to treat BV in women. As BV has not previously been thought to affect men they have not been licensed for use to treat BV in men. Clindamycin cream and oral metronidazole are therefore considered is an experimental treatment for BV in men. This means that they are being tested to see if they are an effective treatment to get rid of BV-associated bacteria in men.

There are two treatment groups in this study. Participants will be given the opportunity to choose what group to participate in, providing the maximum number of participants allowed in that group has not been reached.

1. Dual partner treatment – both the female and her male partner will receive antibiotic treatment.
2. Female only treatment (maximum of 10 couples can participate) – only the female will receive antibiotic treatment. Her male partner will not be asked to take any antibiotics.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 80302 0
A/Prof Catriona Bradshaw
Address 80302 0
Melbourne Sexual Health Centre
Alfred Health
580 Swanston St
Carlton Victoria, 3053
Country 80302 0
Australia
Phone 80302 0
+61 3 9341 6253
Fax 80302 0
+61 3 9341 6757
Email 80302 0
cbradshaw@mshc.org.au
Contact person for public queries
Name 80303 0
A/Prof Catriona Bradshaw
Address 80303 0
Melbourne Sexual Health Centre
Alfred Health
580 Swanston St
Carlton Victoria, 3053
Country 80303 0
Australia
Phone 80303 0
+61 3 9341 6253
Fax 80303 0
+61 3 9341 6757
Email 80303 0
cbradshaw@mshc.org.au
Contact person for scientific queries
Name 80304 0
A/Prof Catriona Bradshaw
Address 80304 0
Melbourne Sexual Health Centre
Alfred Health
580 Swanston St
Carlton Victoria, 3053
Country 80304 0
Australia
Phone 80304 0
+61 3 9341 6253
Fax 80304 0
+61 3 9341 6757
Email 80304 0
cbradshaw@mshc.org.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Deidentified microbiota sequencing data will be publicly available
When will data be available (start and end dates)?
Sequencing data will be made available at time of publication
Available to whom?
Sequencing data will be made publicly available on a repository such as Short Read Archive (SRA) as is standard practice. Sequencing data only contains information related to bacterial sequences and only limited meta-data would be included - no identifying information will be included. The sequencing data will be deidentified and will be given a new ID code.
Available for what types of analyses?
The data would be available for microbiota analysis.
How or where can data be obtained?
The data will be publicly available on a repository such as Short Read Archive (SRA)
What supporting documents are/will be available?
Study protocol
How or where can supporting documents be obtained?
Type [1] 7570 0
Study protocol
Citation [1] 7570 0
The study protocol will be made available when the manuscript is published.
Link [1] 7570 0
Email [1] 7570 0
Other [1] 7570 0
Attachment [1] 7570 0
Summary results
Have study results been published in a peer-reviewed journal?
No
Other publications
Have study results been made publicly available in another format?
No
Results – basic reporting
Results – plain English summary