A product containing healthy vaginal bacteria has proved effective against recurrent bacterial vaginosis (BV), an extremely common vaginal infection that is associated with preterm birth, HIV infection and problems with in vitro fertilization.
Bacterial vaginosis is one of the most frequent bacterial infections, affecting nearly 30% of women of reproductive age in the US, and anywhere from 15% to 50% of women around the world. It is associated with the spread of HIV in Africa, where women make up the majority of those infected, as well as preterm birth and low-birth weight around the world.
The findings come from a Phase IIB trial of LACTIN-V, a so-called “live bio-therapeutic,” conducted at University of California – San Francisco, University of California – San Diego, Rush University Medical Centre in Chicago, and Washington University in St Louis.
The randomised, placebo-controlled, double-blind trial showed a significant reduction in the recurrence of BV and found no safety risks from the bacteria used in the LACTIN-V formulation of the species Lactobacillus crispatus CTV-05, a common bacterium found in healthy vaginal microbiomes.
While BV is commonly treated with an antibiotic called metronidazole, up to three-quarters of women get the infection again within three months. The study found that LACTIN-V reduced these recurrences significantly. Just 30% of women who were given LACTIN-V after initial antibiotic treatment had a recurrence within 12 weeks, compared to 45% of the women who received the antibiotic and a placebo.
LACTIN-V comes in a powder form that women self-administer with a vaginal applicator. Once the healthy bacteria in the powder colonize the vagina, they produce lactic acid, which inhibits the growth of bacteria associated with BV. LACTIN-V is stable for more than a year at room temperature, and more than two years in the refrigerator.
The 228 women in the trial used LACTIN-V once a day for five days, and then twice a week for 10 weeks. Researchers said the product’s ease of use could make it an ideal medication for women around the world.
“The initial indication for LACTIN-V is for the prevention of BV, which millions of women in the US have each year,” said first author of the paper and study lead Dr Craig Cohen, professor of obstetrics, gynaecology and reproductive sciences at UCSF. “But this product also has the potential to be an effective intervention to prevent HIV infection and preterm birth.”
Before LACTIN-V can be used, however, the US Food and Drug Administration (FDA) is likely to require a successful Phase III trial with more participants.
“This is an entirely new approach that strengthens the vaginal microbiome against infections,” said Dr Anke Hemmerling, a researcher at UCSF and the senior author of the new study. “This could be a breakthrough for the long-term prevention of BV.”
Background: Bacterial vaginosis affects 15 to 50% of women of reproductive age, and recurrence is common after treatment with an antibiotic agent. The high incidence of recurrence suggests the need for new treatments to prevent recurrent bacterial vaginosis.
Methods: We conducted a randomized, double-blind, placebo-controlled, phase 2b trial to evaluate the ability of Lactobacillus crispatus CTV-05 (Lactin-V) to prevent the recurrence of bacterial vaginosis. Women 18 to 45 years of age who had received a diagnosis of bacterial vaginosis and who had completed a course of vaginal metronidazole gel as part of the eligibility requirements were randomly assigned, in a 2:1 ratio, to receive vaginally administered Lactin-V or placebo for 11 weeks; follow-up occurred through week 24. The primary outcome was the percentage of women who had a recurrence of bacterial vaginosis by week 12.
Results: A total of 228 women underwent randomization: 152 to the Lactin-V group and 76 to the placebo group; of these participants, 88% in the Lactin-V group and 84% in the placebo group could be evaluated for the primary outcome. In the intention-to-treat population, recurrence of bacterial vaginosis by week 12 occurred in 46 participants (30%) in the Lactin-V group and in 34 participants (45%) in the placebo group (risk ratio after multiple imputation for missing responses, 0.66; 95% confidence interval [CI], 0.44 to 0.87; P=0.01). The risk ratio for recurrence by week 24 (also calculated with multiple imputation for missing responses) was 0.73 (95% CI, 0.54 to 0.92). At the 12-week visit, L. crispatus CTV-05 was detected in 79% of participants in the Lactin-V group. The percentage of participants who had at least one adverse event related to Lactin-V or placebo by week 24 did not differ significantly between the groups. The percentage of participants with local or systemic adverse events was similar in the two groups.
Conclusions: The use of Lactin-V after treatment with vaginal metronidazole resulted in a significantly lower incidence of recurrence of bacterial vaginosis than placebo at 12 weeks.
Craig R Cohen, Michael R Wierzbicki, Audrey L French, Sheldon Morris, Sara Newmann, Hilary Reno, Lauri Green, Steve Miller, Jonathan Powell, Thomas Parks, Anke Hemmerling