Title: Dequalinium versus usual care antibiotics for the treatment of bacterial vaginosis (DEVA): a multicentre randomised, open label, non-inferiority trial
Funder: Department of Health and Social Care

Abstract: Bacterial vaginosis (BV) causes a vaginal discharge that has an unpleasant smell. It is the most common cause of discharge and up to a third of women will get it at some time in their lives. We do not know why BV occurs but there is a change in the balance of the vaginal bacteria with a reduction in the ‘good’ bacteria that protect against infections and an increase in many other bacteria. Current treatments often do not not cure BV completely, but treating BV is important as the symptoms are unpleasant. Also, it can cause miscarriage, premature birth and it increases the risk of catching HIV and other sexually transmitted infections._x000D_ _x000D_ Oral or vaginal antibiotics are recommended for treating BV. These can cause side-effects such as dizziness, nausea and vaginal soreness. Over 1 in 5 women get BV back within one month of treatment and have to take repeated courses of antibiotics. Concern about bacteria becoming resistant to antibiotics and damage to the body’s good bacteria means that non-antibiotic therapies are being considered for BV. _x000D_ _x000D_ There is a new treatment available for BV called dequalinium which works as a vaginal antiseptic. Its potential advantages are that it will not damage the good bacteria throughout the body or cause antibiotic resistance. Two studies have suggested that it could be effective and safe but the number of women included were small so the results were not conclusive. Also, dequalinium is more expensive than some of the usual care antibiotics. _x000D_ _x000D_ The aim of this study, called DEVA, is to see if dequalinium is as good at treating BV as current BV antibiotics. _x000D_ _x000D_ Our study will be involve 904 women diagnosed with BV at one of 15 UK sexual health clinics. Women will be divided in two groups at random to allow a direct and fair comparison. Half will be asked to use dequalinium vaginal pessaries for 6-nights and the other half will be asked to use a standard BV antibiotic treatment recommended by their doctor from the UK National BV Guideline._x000D_ _x000D_ The main purpose of the trial is to see if the BV symptoms have cleared 30-days after the start of treatment. This will be confirmed in a subgroup of women (who will have consented to take their own vaginal swabs at home and post them to us) by looking at a sample of vaginal discharge under a microscope as this is the most accurate way of diagnosing BV. We will also ask about the amount of treatment used, and the side effects and the acceptability of the treatment. All the women will be contacted 3-months after their treatment to see if the BV symptoms came back. We will ask the women to complete two confidential online questionnaires 30-days and 3 months after treatment in order to collect information from them. Finally, we will compare the overall costs of each treatment option and work out which represents the best value for money for the NHS. _x000D_ _x000D_ The study will will be large enough to tell us whether dequalinium is as good as current BV treatments. It will take 3 and a half years from starting the study to produce the final report. _x000D_ _x000D_ Patient input to the trial design was obtained from a focus group of seven women and a survey of 60 sexual health service users. Service users will also be involved in reviewing patient information for the trial and be invited to join the trial steering committee._x000D_ _x000D_ The study results will be presented at medical conferences, be published in medical journals and be sent to the writers of guidelines on the management of BV.

Lay abstract: Research question: Is dequalinium effective in resolving the symptoms of bacterial vaginosis (BV) compared to usual care antibiotics?_x000D_ Background: BV is the commonest cause of vaginal discharge. Usual care antibiotics produce resolution rates of 61-94% 30-days after treatment but recurrences are common. Dequalinium is a broad-spectrum antiseptic which has good activity against BV bacteria._x000D_ Aim: To determine if dequalinium is effective in the management of BV compared to usual care antibiotics_x000D_ Objectives:_x000D_ To determine:_x000D_ • The efficacy of dequalinium in resolving BV compared with usual care antibiotics_x000D_ • The side effects, acceptability of, and adherence to, dequalinium compare with usual care antibiotics_x000D_ • The cost to the NHS of using dequalinium versus usual care antibiotics_x000D_ Methods_x000D_ Design: Multi-centre, randomised, open-label, parallel, non-inferiority trial _x000D_ Setting: 15 UK Genitourinary Medicine (GUM) clinics _x000D_ Population: Women with symptomatic BV either first or recurrent episode _x000D_ Intervention: Dequalinium chloride 10mg vaginal tablet for 6 nights _x000D_ Control: Any UK guideline recommended oral or topical antibiotic treatment for BV. Clinicians will choose the comparator treatment prior to randomisation_x000D_ Outcomes _x000D_ Primary: Patient reported resolution of symptoms 30 days after starting treatment_x000D_ Secondary:_x000D_ Time to resolution of symptoms_x000D_ Microscopic resolution of BV at 30-days (in a subgroup of participants)_x000D_ Adherence to treatment_x000D_ Side effects and acceptability of treatment_x000D_ Patient reported recurrence of symptoms within 3-months_x000D_ Time to recurrence of BV symptoms_x000D_ Costs of treatment_x000D_ Sample size: Assuming 78% of participants have BV symptom resolution at 30-days in both control and intervention groups, a total sample size of 722 for analysis (361 in each group) will achieve 90% power to detect non-inferiority with a lower confidence limit for the absolute risk difference of 10%, with a 1-sided significance level of 0.025. To allow a loss of primary outcome data of up to 20% the trial will recruit 904 women. A 10% lower confidence interval for the risk of difference was acceptable to 68% of a sample of women attending two GUM clinics and 81% of clinicians experienced in treating BV._x000D_ Cost comparison: The costs associated with dequalinium will be compared with usual care antibiotics. The primary objective is to determine the non-inferiority of dequalinium so the economic analysis will focus on whether using dequalinium rather than usual care antibiotics is cost-neutral. Resource use and costs will be collected in both arms of the trial._x000D_ Timelines for delivery (42 months): 9 months setup, 21 months recruitment, 3 month follow-up, 2 month data cleaning, 7 months analysis and write up. An internal pilot at 9 months post first participants randomised will review the number of participants recruited and completing the 30-day assessment, and adherence, against pre-specified targets. Following staggered site set up recruitment will be 4 participants per month per site. In 2016 Leeds GUM clinic diagnosed 90 cases of BV per month so this target is realistic for 15 sites of varying size and research capacity._x000D_ Anticipated impact and dissemination: If dequalinium is effective in treating BV it will result in reduced antibiotic use for this common condition. The results will be presented at medical conferences, published in medical journals and highlighted to the authors of national and international BV management guidelines.

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: INFECTION