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Trial registered on ANZCTR


Registration number
ACTRN12613001147774
Ethics application status
Approved
Date submitted
10/10/2013
Date registered
15/10/2013
Date last updated
11/06/2019
Date data sharing statement initially provided
11/06/2019
Date results information initially provided
11/06/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Randomised controlled trial of the oral contraceptive pill use to reduce bacterial vaginosis (BV) recurrence following recommended antibiotic therapy
Scientific title
In women with bacterial vaginosis (BV), does taking the oral contraceptive pill in addition to recommended antibiotic therapy, compared to taking recommended antibiotic therapy alone, reduce the risk of BV recurrence?
Secondary ID [1] 283364 0
Nil
Universal Trial Number (UTN)
U1111-1148-7961
Trial acronym
SToPBV: Strategies to prevent bacterial vaginosis
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Bacterial vaginosis 290262 0
Condition category
Condition code
Infection 290652 290652 0 0
Sexually transmitted infections

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a randomised controlled open-label trial of the oral contraceptive pill for prevention of BV recurrence following recommended antibiotic therapy. All participants in this trial will be given current recommended antibiotic treatment for BV, in keeping with standard of care, prior to being assessed for eligibility for the trial. This antibiotic will predominantly be metronidazole orally 400 mg twice a day for 7 days, however, clinicians will be able to prescribe a 7-day regimen of oral or vaginal clindamycin, which has equivalent efficacy, if patients are unable to tolerate metronidazole or it is contraindicated.

Intervention:
Arm one: Combined oestrogen and progesterone containing oral contraceptive pill (OCP) commencing on day 8 and administered for six months.

Randomisation will be occurring for the OCP which will be a standard monophasic 30mcg ethinyl oestradiol pill with 150 mcg of levonorgesterol, unless otherwise clinically indicated, or preferred by the participant or clinician. It will be prescribed in the standard 21 day active, 7 day placebo pill regimen.

Adherence to the OCP will be monitored by monthly self-report within questionnaires.
Intervention code [1] 288089 0
Treatment: Drugs
Comparator / control treatment
The control group will not receive the intervention of the oral contraceptive pill for 6 months, however will receive standard recommended antibiotic treatment (ie oral metronidazole for 7 days) in keeping with standard clinical care.
Control group
Active

Outcomes
Primary outcome [1] 290668 0
Recurrence of BV defined as 3-4/4 Amsel criteria and a Nugent score of 4-10.
Timepoint [1] 290668 0
within 6 months of randomisation
Secondary outcome [1] 305002 0
Recurrence of BV defined by Amsel method (3-4/4 Amsel criteria) and Nugent score 4-10
Timepoint [1] 305002 0
within 3 months of randomisation
Secondary outcome [2] 305003 0
Recurrence of BV defined by Nugent score 7-10
Timepoint [2] 305003 0
at 1 month, and within 3 and 6 months, of randomisation

Eligibility
Key inclusion criteria
Women will be eligible if they:
i) Are 18-45 years of age,
ii) Are symptomatic with BV, defined as a Nugent score of 4-10 and 3-4 Amsel criteria,
Minimum age
18 Years
Maximum age
45 Years
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
Women will be ineligible if they are:
i) concurrently diagnosed with pelvic inflammatory disease (PID)
ii) confirmed to be pregnant at the time of recruitment, or wish to conceive within the next 6 months,
iii) known to be HIV positive,
iv) unwilling or unable to comply with the requirements of the study protocol,
v) already currently using a hormonal method of contraception,
vi) known to have contraindications to OCP according to WHO criteria (e.g. focal migraine, history of deep venous thrombosis [DVT], hypertension etc)

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)
Sampling frame:
Women for this study will be recruited from Melbourne Sexual Health Clinic (MSHC), and referred to the service from Family Planning Victoria (FPV) and local general practices which specialise in women’s health. MSHC is the largest sexual health service in Victoria and diagnoses 500-550 cases of BV annually and has established relationships with FPV and local general practices.

Randomisation:
Women that consent will be randomly assigned to one of the two study arms using a computer-generated sequence. A researcher, with no clinical input into this trial, will generate and hold the random number sequence. Randomisation will occur in blocks to ensure that the allocation of women to the two arms occurs at a similar rate over the recruitment period.

Allocation concealment: Once a woman is enrolled in the study, the research nurse will open the next consecutive sealed envelope to determine her group allocation.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
A researcher, with no clinical input into this trial, will generate and hold the random number sequence. Randomisation will occur in blocks to ensure that the allocation of women to the two arms occurs at a similar rate over the recruitment period.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2 / Phase 3
Type of endpoint/s
Efficacy
Statistical methods / analysis
Data will be analysed using STATA and SPSS. Cumulative recurrence of BV will be determined for the overall study population and by randomisation group at each interval of follow-up. Proportions will be compared using Chi-square and Fisher’s Exact tests where appropriate, and 95% confidence intervals (CIs) will be calculated. All statistical tests will be two-sided and a level of p<0.05 considered significant. Kaplan-Meier methods will be used to generate survival curves and estimate time until BV recurrence by randomisation group. The log rank test will be used to compare survival distributions between the two randomised groups. Cox proportional hazards models will be used to estimate the hazard ratio and 95% CIs for the effect of randomisation assignment on time to first BV recurrence. The primary analysis will be an intention to treat. Secondary analyses will include modified intention to treat and per-protocol analyses, and multivariate and cox regression analyses to account for any differences in baseline characteristics between treatment groups, and for factors known to be clinically-associated with BV recurrence.

With a total sample size of 266 (133 per group) we will have 80% power to detect a 40% reduction in BV recurrence from 40% in the control group to 24% in the OCP group (2-alpha=5%). Assuming a six month loss to follow-up of 15% in keeping with our previous trials, 314 women will be recruited (157 per arm).

Recruitment
Recruitment status
Stopped early
Data analysis
Data collected is being analysed
Reason for early stopping/withdrawal
Lack of funding/staff/facilities
Date of first participant enrolment
Anticipated
1/11/2013
Actual
2/07/2014
Date of last participant enrolment
Anticipated
Actual
2/03/2016
Date of last data collection
Anticipated
2/09/2016
Actual
24/08/2016
Sample size
Target
314
Accrual to date
Final
95
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 1580 0
The Alfred - Prahran
Recruitment postcode(s) [1] 7415 0
3053 - Carlton

Funding & Sponsors
Funding source category [1] 288092 0
Government body
Name [1] 288092 0
National Health and Medical Research Council (NHMRC)
Country [1] 288092 0
Australia
Funding source category [2] 288093 0
University
Name [2] 288093 0
The University of Melbourne
Country [2] 288093 0
Australia
Funding source category [3] 297320 0
University
Name [3] 297320 0
Monash University Central Clinical School
Country [3] 297320 0
Australia
Primary sponsor type
University
Name
The University of Melbourne
Address
Grattan St, Parkville, Vic 3010
Country
Australia
Secondary sponsor category [1] 286839 0
Hospital
Name [1] 286839 0
Alfred Health
Address [1] 286839 0
55 Commercial Road, Melbourne, Vic 3004
Country [1] 286839 0
Australia
Secondary sponsor category [2] 296291 0
University
Name [2] 296291 0
Monash University
Address [2] 296291 0
Monash University Central Clinical School
Level 6 of the Alfred Centre
99 Commercial Rd, Melbourne VIC 3004
Country [2] 296291 0
Australia
Other collaborator category [1] 277644 0
Government body
Name [1] 277644 0
Burnet Institute
Address [1] 277644 0
A/Prof Gilda Tachedjian
Burnet Institute
85 Commercial Road
Melbourne
Victoria
3004
Country [1] 277644 0
Australia
Other collaborator category [2] 277645 0
University
Name [2] 277645 0
The University of Sydney
Address [2] 277645 0
Dr Jim Manos
Department of Infectious Diseases & Immunology, Sydney Medical School
The University of Sydney
Room 671, Blackburn Building D06,
The University of Sydney, NSW, 2006
Country [2] 277645 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 290017 0
The Alfred Health Human Ethics Committee
Ethics committee address [1] 290017 0
The Alfred Hospital, 55 Commercial Road, Melbourne, Victoria 3004, Australia
Ethics committee country [1] 290017 0
Australia
Date submitted for ethics approval [1] 290017 0
04/09/2013
Approval date [1] 290017 0
08/10/2013
Ethics approval number [1] 290017 0
404/13

Summary
Brief summary
OVERALL AIM: This randomised controlled trial is aiming to establish if women who take the oral contraceptive pill (OCP) have a lower risk of getting bacterial vaginosis back again (called BV relapse or recurrence) after routine recommended antibiotic treatment.

OTHER AIMs: we also aim to determine the mechanisms, or reasons, as to how using the OCP may be reducing women’s risk of getting BV back again. This will involve exploring the effects of oral contraception on healthy vaginal bacteria and BV-associated bacteria, and the effects on natural vaginal sugars and acids and immune markers.

BACKGROUND AND SIGNIFICANCE: Bacterial vaginosis is the commonest causes 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 and low birth weight, pelvic infection, and increased susceptibility to HIV and sexually transmitted infections (STIs). We have shown that BV relapse is common even after recommended treatment. However, we have found in two studies that women using combined (oestrogen & progesterone containing) hormonal contraception appeared to have half the risk of BV recurrence following recommended antibiotics compared to women not taking the pill. We further confirmed this finding by meta-analysis of published literature in which we showed that in 55 studies, women using hormonal contraception had a reduced risk of BV recurrence. However, no randomised controlled trials have been conducted and how hormonal contraception reduces a women’s risk of BV is unknown. We hypothesise that this could be happening via different mechanisms/actions such as increasing the levels of natural vaginal acids and by altering the vaginal immune response which may cause normally occurring “healthy” vaginal bacteria to increase and for less healthy BV-associated bacteria to decrease.

HOW WILL WE DO THIS: This is a trial of 314 women who have been diagnosed with BV and prescribed the standard antibiotic treatment. Half of the participants (157 women) will be randomised to the oral contraceptive pill for 6 months, and the other half to no OCP for 6 months. We anticipate that those who take the pill will have a reduced risk of getting BV back again but this remains to be proven in this trial.
Trial website
http://www.mshc.org.au/stopbv/
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 43494 0
A/Prof Catriona Bradshaw
Address 43494 0
Melbourne Sexual Health Centre
Alfred Health
580 Swanston St
Carlton Victoria, 3053
Country 43494 0
Australia
Phone 43494 0
+61 3 9341 6253
Fax 43494 0
+61 3 9347 6757
Email 43494 0
[email protected]
Contact person for public queries
Name 43495 0
Catriona Bradshaw
Address 43495 0
Melbourne Sexual Health Centre
Alfred Health
580 Swanston St
Carlton Victoria, 3053
Country 43495 0
Australia
Phone 43495 0
+61 3 9341 6253
Fax 43495 0
+61 3 9347 6757
Email 43495 0
[email protected]
Contact person for scientific queries
Name 43496 0
Catriona Bradshaw
Address 43496 0
Melbourne Sexual Health Centre
Alfred Health
580 Swanston St
Carlton Victoria, 3053
Country 43496 0
Australia
Phone 43496 0
+61 3 9341 6253
Fax 43496 0
+61 3 9347 6757
Email 43496 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
TypeIs Peer Reviewed?DOICitations or Other DetailsAttachment
Study results articleYes L A. Vodstrcil, E Plummer, C K. Fairley, G Tached... [More Details] 365109-(Uploaded-11-06-2019-09-17-09)-Journal results publication.pdf

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseCombined oral contraceptive pill-exposure alone does not reduce the risk of bacterial vaginosis recurrence in a pilot randomised controlled trial.2019https://dx.doi.org/10.1038/s41598-019-39879-8
N.B. These documents automatically identified may not have been verified by the study sponsor.