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Trial registered on ANZCTR


Registration number
ACTRN12622001431718
Ethics application status
Approved
Date submitted
18/10/2022
Date registered
8/11/2022
Date last updated
7/10/2023
Date data sharing statement initially provided
8/11/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
Partner Cohort Treatment Study (PACT study) for bacterial vaginosis
Scientific title
A pilot randomised Partner Cohort Treatment Study for monogamous couples who are in the LGBTQIA+ community, where one person has bacterial vaginosis
Secondary ID [1] 306833 0
none
Universal Trial Number (UTN)
U1111-1284-0518
Trial acronym
BV PACT Study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
bacterial vaginosis 325918 0
Condition category
Condition code
Infection 323232 323232 0 0
Other infectious diseases
Renal and Urogenital 325059 325059 0 0
Other renal and urogenital disorders
Reproductive Health and Childbirth 325060 325060 0 0
Other reproductive health and childbirth disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The PACT study is a partner-treatment study for monogamous couples who are in the LGBTQIA+ community, where one person has a vagina and is diagnosed with bacterial vaginosis (BV) and their partner, regardless of their genitals or their gender identity (excluding cisgender-men). All couple will receive treatment, as outlined below.

Initially, participants will be asked if they have any allergies or contraindications prior to determination of their treatment. Couples will be treated with the same regimen in most cases (with some exceptions, see below).

If both partners have a vagina and can tolerate both first-line medications: both will be randomised to one of two treatment groups:

Group 1: Both receive oral metronidazole 400mg twice daily for 7 days

Group 2: Both receive combination of oral metronidazole 400mg twice daily for 7 days AND clindamycin 2% cream intravaginally once a day at night for 7 nights

If one or both partners cannot tolerate oral metronidazole or topical clindamycin cream, they will both receive treatment with the regimen that one/both can tolerate (i.e. both will receive oral metronidazole 400mg twice daily for 7 days, or both will receive topical clindamycin cream intravaginally once daily at night for 7 nights).

Couples will be excluded from the primary analysis and not form part of the main evaluation group in the following circumstances:
• Partner with a vagina who does not have BV and declines treatment; The couples will still be followed for 9 weeks and asked to self-collect specimens and complete questionnaires. This sub-group will be able to access treatment at a later time point if they request it.
• Partner with a penis; The participant will receive oral metronidazole 400mg twice daily and topical 2% clindamycin cream to be applied to the glans penis (under the foreskin if uncircumcised) and upper shaft twice daily (morning and night) for 7 days.
• Partner with a neovagina; The participant will receive oral metronidazole 400mg twice daily and topical 2% intravaginal clindamycin cream once a day at night for 7 nights.
• Partner with a vagina taking testosterone; The participant will receive antibiotics with partner as randomised above.

All participants will be sent an SMS the day after they are due to finish treatment which will ask about their adherence to the treatment/s they received.
Intervention code [1] 324657 0
Treatment: Drugs
Comparator / control treatment
The control arm is couples receiving mono-therapy with oral metronidazole 400mg twice daily for 7 days (i.e. group 1)
Control group
Active

Outcomes
Primary outcome [1] 332834 0
The acceptability, tolerability and adherence to concurrent partner treatment (whole population) as a composite outcome.
Adherence and tolerability will be assessed by audit of participant questionnaire designed specifically for this study and to be filled-out the day after treatment is expected to be completed (i.e. day 8). Acceptability will be assessed by audit of participation in the trial by partners of an index with bacterial vaginosis diagnosed - i.e. proportion of index BV participants whose partners received treatment.
Timepoint [1] 332834 0
Adherence tolerability and acceptability will be assessed at day 8 post-intervention commencement
Primary outcome [2] 332836 0
Establish the effect of both treatment strategies on the genital microbiota of couples using genomic sequencing of genital swabs.
Timepoint [2] 332836 0
This will be assessed at baseline, and day 8 as well as weekly for 9 weeks post-treatment commencement. All specimens will be included.
Secondary outcome [1] 414817 0
1) BV recurrence within 9 weeks of treatment in all study groups/populations. This will be assessed using vaginal smears provided each week by participants, which will undergo Nugent scoring by an experienced microscopist. Two sequential Nugent scores of 7-10 will indicate BV.
Timepoint [1] 414817 0
Recurrence will be assessed weekly for 9 weeks post-treatment commencement
Secondary outcome [2] 414818 0
2) BV recurrence within 4 weeks of treatment in all study groups/populations.
BV will be assessed using vaginal smears provided each week by participants, which will undergo Nugent scoring by an experienced microscopist. Two sequential Nugent scores of 7-10 will indicate BV.
Timepoint [2] 414818 0
Recurrence will be assessed weekly for 4 weeks post-treatment commencement
Secondary outcome [3] 414819 0
3) BV recurrence within 9 weeks of treatment assessed separately (stratified) according to treatment regimen (Arm 1 and 2)
BV will be assessed using vaginal smears provided each week by participants, which will undergo Nugent scoring by an experienced microscopist. Two sequential Nugent scores of 7-10 will indicate BV. The two treatment arms will not be able to be directly compared but the findings will be used to generate recurrence rates and confidence intervals by treatment arm.
Timepoint [3] 414819 0
Recurrence will be assessed weekly for 9 weeks post-treatment commencement
Secondary outcome [4] 414820 0
4) The acceptability, tolerability and adherence will be assessed as a composite secondary outcome. The findings will be stratified by the two different treatment regimens in the principal study population (Arm 1 and 2).
Adherence and tolerability will be assessed by audit of participant questionnaire administered the day after treatment is expected to be completed (i.e. day 8) - this questionnaire has been designed for this study.

Acceptability will be assessed by audit of participation in the trial by partners of an index with bacterial vaginosis diagnosed (e.g. proportion of index BV participants whose partners also received treatment). These data will be separately assessed according to treatment arm.
Timepoint [4] 414820 0
Adherence tolerability and acceptability will be assessed at day 8 post-intervention commencement
Secondary outcome [5] 414821 0
5) The effect of treatment on the genital microbiome of couples over 9 weeks, assessed by (stratified) the two different treatment regimens in the principal study population (Arm 1 and 2), using genomic sequencing of genital swabs. This outcome may not be statistically powered to directly compare the two arms, however the results will be separately analysed.
Timepoint [5] 414821 0
This will be assessed at baseline, and day 8 as well as weekly for 9 weeks post-treatment commencement. All specimens will be included.
Secondary outcome [6] 414822 0
6) The effect of concurrent partner treatment on the oral microbiome of couples over 9 weeks (including oral specimens from both the index with BV at enrolment and partner), using genomic sequencing of saliva samples.
Timepoint [6] 414822 0
This will be assessed at baseline, and day 8 as well as weekly for 9 weeks post-treatment commencement. All oral specimens will be included.
Secondary outcome [7] 414983 0
7) The effect of concurrent partner treatment on the gut microbiome of couples over 9 weeks (including specimens from both the index with BV at enrolment and partner), using genomic sequencing of rectal swabs.
Timepoint [7] 414983 0
This will be assessed at baseline, and day 8 as well as weekly for 9 weeks post-treatment commencement. All rectal swab specimens will be included.

Eligibility
Key inclusion criteria
Index participants will be eligible if they are:
i) Are diagnosed with BV
ii) Aged 18 years to pre-menopausal (i.e. not more than 12 consecutive months after the last menstrual period/menopause)
iii) Have an partner who meets the study criteria
iv) Sufficient English to understand study procedures
v) Provide written informed consent and is willing to comply with study procedures
vi) Able to complete study protocol requirements

The partner will be eligible if they:
i) Have an partner (the index) who has been diagnosed with BV (they do not need to have a BV diagnosis as well)
ii) Are aged 18 years or older
iii) For partners of an index who attended clinic: enrol within 3 business days of their partner being diagnosed with BV (or the index agrees to waits before starting treatment so that couples are aligned with therapy)
iv) For partners at home: return baseline procedures/screening packs to determine BV-status if applicable
v) Have sufficient English to understand study procedures
vi) Provide written informed consent and is willing to comply with study procedures
vii) Able to complete study protocol requirements
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Participants will be ineligible if they:
i) Are confirmed to be pregnant or breastfeeding, or planning to conceive in the next 9 weeks
ii) Are unwilling or unable to comply with the requirements of the study protocol
iii) Have other concurrent sexual partners
iv) Are a current sex worker
v) Have an allergy or contraindication to both first-line antibiotics for BV, metronidazole, and clindamycin
vi) Have taken metronidazole or clindamycin in the 2 weeks prior to enrolment
vii) Are being prescribed 14 days of metronidazole for PID treatment
Additionally, the partner will be ineligible if they:
i) Identify as a cis-gender male and have a cis-gender female partner (heterosexual couples will be offered participation in Step Up RCT, ANZCTR: ACTRN12619000196145 )
ii) Had metronidazole in the week prior to enrolment or are being prescribed 14d of metronidazole for PID treatment
iii) Has a contraindication/allergy that means they cannot receive treatment

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
After performing the screening and eligibility assessments, the research nurse will confirm whether the couple are eligible to receive either treatments (mono or combo-therapy). In the trial password-protected online database (REDCap hosted and managed by HELIX at Monash University), the research nurse will then click "randomise" to find out the group that the couple are allocated to.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
For couples eligible for randomisation, a randomisation sequence will be generated by an independent biostatistician and a staff member will upload the sequence to the online database, REDCap. A 1:1 randomisation ratio, in blocks of size four-six will be used. The randomisation allocation button will only be visible once all the required information has been entered and the couple are deemed eligible. REDCap will then retrieve the next ‘sealed’ allocation.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
All couples will be randomised to treatment, unless the require genital-directed treatment or have a contraindication (these couples will receive the treatment they can tolerate or that is appropriate for their genitals).

If a protocol violation occurs after randomisation (defined above), reasons will be collected, and the participant will be deemed either lost to follow up or withdrawal if this is formally what they decide to do. Couples who fail screening will not be included in the evaluable population for analyses and therefore the next “sealed” allocation can be used to recruit an additional couple.

As this is an open-label RCT, both the research nurse performing randomisation and the participants will know which group they are in. However, the microscopists performing Nugent scoring and Clue cell reporting will be blinded to the treatment that the couple receive and therefore the primary outcome is blinded to those reporting it.

Phase
Phase 3
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Analysis of primary and secondary outcomes
Data will be transferred to STATA for analysis. Kaplan Meier methods will be used to generate survival curves for time until recurrence of BV for index participants and to abnormal microbiota (i.e. a genital microbiota dominated by BV-associated bacteria). Recurrence rates and their 95% CI will be calculated for all treated couples combined, regardless of treatment. Additional risk factors associated with recurrence of BV will be investigated using Cox regression. Rate ratios and robust standard errors will be calculated using this methodology.

While we will generate efficacy estimates with 95%CI for the two treatment arms, we will not be powered to compare the two different treatment arms, so we will look at the recurrence rates between the two groups as a sensitivity analysis.

Microbiota analysis
The exact methods used are to be determined, but all microbiota analysis will be conducted with the aim of characterising the genital, oral and gut microbiota, and will be conducted on samples that are coded with a unique identifier, date of birth and date of collection only.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
9/10/2023
Actual
Date of last participant enrolment
Anticipated
31/12/2025
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
148
Accrual to date
0
Final
Recruitment in Australia
Recruitment state(s)
ACT,NSW,NT,QLD,SA,TAS,WA,VIC
Recruitment hospital [1] 23378 0
Melbourne Sexual Health Centre (MSHC) - Carlton
Recruitment postcode(s) [1] 38775 0
3053 - Carlton

Funding & Sponsors
Funding source category [1] 311163 0
Government body
Name [1] 311163 0
National Health and Medical Research Council Australia
Country [1] 311163 0
Australia
Primary sponsor type
University
Name
Monash University
Address
Level 1, Chancellery Building D
26 Sports Walk, Clayton Campus, Wellington Rd
Clayton 3800
VIC
Country
Australia
Secondary sponsor category [1] 314083 0
None
Name [1] 314083 0
Address [1] 314083 0
Country [1] 314083 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 310693 0
Alfred Hospital HREC
Ethics committee address [1] 310693 0
Office of ethics and research governance
Level 5, 553 St Kilda Rd,
Melbourne 3004
VIC
Ethics committee country [1] 310693 0
Australia
Date submitted for ethics approval [1] 310693 0
22/08/2022
Approval date [1] 310693 0
18/10/2022
Ethics approval number [1] 310693 0
456/22
Ethics committee name [2] 313958 0
ACON Ethics Committee
Ethics committee address [2] 313958 0
414 Elizabeth St Surry Hills NSW 2010
Ethics committee country [2] 313958 0
Australia
Date submitted for ethics approval [2] 313958 0
27/04/2023
Approval date [2] 313958 0
02/06/2023
Ethics approval number [2] 313958 0
202309

Summary
Brief summary
Current first-line antibiotic therapies for bacterial vaginosis (BV) provide cure rates of 70-80% 1 month after treatment, but >50% experience BV recurrence within 3-6 months of completing recommended treatment. There is epidemiological and microbiological evidence supporting sexual exchange of vaginal bacteria (both optimal and non-optimal) between sexual partners. BV imposes a heavy burden on the healthcare system, as recurrence results in multiple presentations to clinical services and repeated antibiotic use. In addition, the obstetric and reproductive sequelae associated with BV have significant implications for healthcare expenditure. Effective therapeutic approaches are an urgent health priority.

The LGBTQIA+ community have a higher prevalence of BV in many settings. Given the evidence of sexual exchange of bacteria between partners, treatment of only one individual in a partnership may result in re-infection when sex resumes post-treatment.

Given the high rate of BV in the LGBTQIA+ community, we hypothesise that treating the regular sexual partner of people diagnosed with BV (the index) will reduce BV recurrence. All couples will have access to treatment which will either be randomised to either one or two antibiotics (see below) or genital-directed.

We aim to recruit 74 couples (148 individuals) in Australia, and we are using a randomised study design: half of the couples will receive a single antibiotic, and half will receive combination therapy with two antibiotics. However if you cannot take the antibiotics we will provide an alternative. We will collect genital, oral and anal specimens from all participants before and after treatment, and then weekly for up to 9 weeks to see if the index gets their BV back again or not.
Trial website
https://www.mshc.org.au/research/research-studies/pact-study
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 118534 0
Prof Catriona Bradshaw
Address 118534 0
Melbourne Sexual Health Centre
580 Swanston St
Carlton 3053
VIC
Country 118534 0
Australia
Phone 118534 0
+61 3 93416253
Fax 118534 0
Email 118534 0
catriona.bradshaw@monash.edu
Contact person for public queries
Name 118535 0
Dr Lenka Vodstrcil
Address 118535 0
Melbourne Sexual Health Centre
580 Swanston St
Carlton 3053
VIC
Country 118535 0
Australia
Phone 118535 0
+61 3 93416200
Fax 118535 0
Email 118535 0
stopbv@mshc.org.au
Contact person for scientific queries
Name 118536 0
Dr Lenka Vodstrcil
Address 118536 0
Melbourne Sexual Health Centre
580 Swanston St
Carlton 3053
VIC
Country 118536 0
Australia
Phone 118536 0
+61 3 93416200
Fax 118536 0
Email 118536 0
stopbv@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?
Sequencing data with info specific to bacterial sequences will be publically available. If publishers require meta-data to be uploaded to accompany any related publications, only de-identified data of published results that is not able to be linked to any individual would be considered for data sharing, in alignment with the NHMRC statement. New ID codes would be assigned to any data to be shared.
When will data be available (start and end dates)?
From the publication date for 5 years after publication
Available to whom?
Microbiota data would be publicly available
Other meta-data would be considered by request
Available for what types of analyses?
The data would be available for microbiota analysis.
Additional data sharing may be considered for meta-analyses (however only de-identified pooled data).
How or where can data be obtained?
Any laboratory/microbiota sequencing data will be made publicly available on a repository such as Short Read Archive (SRA) as is standard practice.
Other meta-data may be uploaded with a manuscript as required by the publisher.
Additional data requests can be made to the contact author listed on any publication catriona.bradshaw@monash.edu


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
17390Study protocol    We aim to publish the study protocol. It will outl... [More Details]



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