Randomized trial of multi-strain Lactobacillus crispatus vaginal live biotherapeutic products after antibiotic therapy for bacterial vaginosis: study protocol for VIBRANT (vaginal lIve biotherapeutic RANdomized trial)

Background : Globally, approximately 30 % of women have bacterial vaginosis (BV). Antibiotic treatment is frequently followed by recurrence, likely due to lack of colonization with beneficial lactobacilli. Methods : This is a Phase 1, randomized, placebo-controlled trial of vaginal live biotherapeutic products (LBP) after antibiotic treatment for BV to establish Lactobacillus colonization. The LBP are vaginal tablets containing 6 L. crispatus strains (LC106) or 15 L. crispatus strains (LC115), at 2 x 109 colony forming units (CFU) per dose. Participants with BV in the United States and South Africa will receive seven days of oral metronidazole twice daily and will be randomized 1:1:1:1:1 to: seven days placebo; seven days LC106; three days LC106/four days placebo; seven days LC106 starting day 3 of the metronidazole course; or seven days LC115. Safety will be assessed by the number and percentage of ≥ Grade 2 related adverse events during or after product use. The primary outcome is LBP colonization defined as relative abundance ≥5 % of any LBP strain or ≥10 % of a combination of LBP strains by metagenomic sequencing any time in the 5 weeks after randomization. A generalized linear model will measure the association between treatment group and colonization, adjusting for site. Conclusions : This study seeks to establish proof of concept for a multi-strain LBP to promote vaginal L. crispatus colonization in two geographically distinct populations.