Randomized Trial of Periodic Presumptive Treatment With High-Dose Intravaginal Metronidazole and Miconazole to Prevent Vaginal Infections in HIV-negative Women

Abstract

Background: Vaginal infections are common, frequently recur, and may increase women's risk for sexually transmitted infections (STIs). We tested the efficacy of a novel regimen to prevent recurrent vaginal infections.

Methods: Human immunodeficiency virus (HIV)-negative women 18-45 years old with 1 or more vaginal infections, including bacterial vaginosis (BV), vulvovaginal candidiasis (VVC), or Trichomonas vaginalis (TV), were randomly assigned to receive vaginal suppositories containing metronidazole 750 mg plus miconazole 200 mg or matching placebo for 5 consecutive nights each month for 12 months. Primary endpoints, evaluated every 2 months, were BV (Gram stain) and VVC (positive wet mount and culture).

Results: Participants (N = 234) were randomly assigned to the intervention (N = 118) or placebo (N = 116) arm. Two hundred seventeen (93%) women completed an end-of-study evaluation. The intervention reduced the proportion of visits with BV compared to placebo (21.2% vs 32.5%; relative risk [RR] 0.65, 95% confidence interval [CI] .48-.87). In contrast, the proportion of visits with VVC was similar in the intervention (10.4%) versus placebo (11.3%) arms (RR 0.92, 95% CI .62-1.37).

Conclusions: Monthly treatment with intravaginal metronidazole plus miconazole reduced the proportion of visits with BV during 12 months of follow-up. Further study will be important to determine whether this intervention can reduce women's risk of STIs.

Keywords: Trichomonas vaginalis; bacterial vaginosis; metronidazole; miconazole; periodic presumptive treatment; vulvovaginal candidiasis.

Figure 1.

The figure shows the flow of participants from screening through randomization and follow-up to completion of the study. While the study protocol allowed investigators to exclude women if a medical condition or situation was present, such that participation was not advisable, no exclusions were made based on this criterion alone. In the intervention arm, 30 (25.4%) of 118 women were not included in the per-protocol population; 9 (7.6%) completed less than 4 follow-up examination visits and 21 (17.8%) used less than 48 of 60 possible doses of study product. In the placebo arm, 24 (%) of 116 women were not included in the per-protocol population; 6 (%) completed less than 4 follow-up visits and 16 (%) used less than 48 of 60 possible doses of study product.