Treating male partners of women with bacterial vaginosis (StepUp): a protocol for a randomised controlled trial to assess the clinical effectiveness of male partner treatment for reducing the risk of BV recurrence

Abstract

Background: Bacterial vaginosis (BV) is estimated to affect 1 in 3 women globally and is associated with obstetric and gynaecological sequelae. Current recommended therapies have good short-term efficacy but 1 in 2 women experience BV recurrence within 6 months of treatment. Evidence of male carriage of BV-organisms suggests that male partners may be reinfecting women with BV-associated bacteria (henceforth referred to as BV-organisms) and impacting on the efficacy of treatment approaches solely directed to women. This trial aims to determine the effect of concurrent male partner treatment for preventing BV recurrence compared to current standard of care.

Methods: StepUp is an open-label, multicentre, parallel group randomised controlled trial for women diagnosed with BV and their male partner. Women with clinical-BV defined using current gold standard diagnosis methods (≥3 Amsel criteria and Nugent score (NS) = 4-10) and with a regular male partner will be assessed for eligibility, and couples will then be consented. All women will be prescribed oral metronidazole 400 mg twice daily (BID) for 7 days, or if contraindicated, a 7-day regimen of topical vaginal 2% clindamycin. Couples will be randomised 1:1 to either current standard of care (female treatment only), or female treatment and concurrent male partner treatment (7 days of combined antibiotics - oral metronidazole tablets 400 mg BID and 2% clindamycin cream applied topically to the glans penis and upper shaft [under the foreskin if uncircumcised] BID). Couples will be followed for up to 12 weeks to assess BV status in women, and assess the adherence, tolerability and acceptability of male partner treatment. The primary outcome is BV recurrence defined as ≥3 Amsel criteria and NS = 4-10 within 12 weeks of enrolment. The estimated sample size is 342 couples, to detect a 40% reduction in BV recurrence rates from 40% in the control group to 24% in the intervention group within 12 weeks.

Discussion: Current treatments directed solely to women result in unacceptably high rates of BV recurrence. If proven to be effective the findings from this trial will directly inform the development of new treatment strategies to impact on BV recurrence.

Trial registration: The trial was prospectively registered on 12 February 2019 on the Australian and New Zealand Clinical Trial Registry (ACTRN12619000196145, Universal Trial Number: U1111-1228-0106, https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=376883&isReview=true ).

Keywords: Antibiotic treatment; Bacterial vaginosis; Clindamycin; Couple treatment; Metronidazole; Recurrence; StepUp.

Fig. 1

Participant flow through the study from recruitment to study endpoint. ¹been together ≥8 weeks, indicated/confirmed on phone that RSP likely to participate; ²refer to eligibility criteria; ³protocol violation means not in modified intention-to-treat (mITT) primary analysis or per protocol analysis; ⁴eligible for mITT and per protocol analyses if week 4 and/or 12 provided but with missing data, not eligible for safety analysis; ⁵if female participant does not attend clinic visits but does return a swab, eligible for secondary endpoints; ⁶if female attends at week 4 but not week 12, still be eligible for mITT; if no visits but returns a swab, eligible for secondary endpoints; if no visits or swabs, protocol violation. Abbreviations: LTFU, Loss to follow up; W, withdrawn

Fig. 2

Summary of study schedule and procedures for women and men at each time point