Efficacy and safety of a vaginal medicinal product containing three strains of probiotic bacteria: a multicenter, randomized, double-blind, and placebo-controlled trial

Abstract

Objective: The main objective of this study was to evaluate whether vaginal administration of probiotic Lactobacillus results in their colonization and persistence in the vagina and whether Lactobacillus colonization promotes normalization and maintenance of pH and Nugent score.

Patients and methods: The study was a multicenter, randomized, double-blind, and placebo-controlled trial. Altogether, 376 women were assessed for eligibility, and signed informed consent. One hundred and sixty eligible women with abnormal, also called intermediate, vaginal microflora, as indicated by a Nugent score of 4-6 and pH >4.5 and zero or low Lactobacillus count, were randomized. Each participant was examined four times during the study. Women were randomly allocated to receive either the probiotic preparation inVag(®), or a placebo (one capsule for seven consecutive days vaginally). The product inVag includes the probiotic strains Lactobacillus fermentum 57A, Lactobacillus plantarum 57B, and Lactobacillus gasseri 57C. We took vaginal swabs during visits I, III, and IV to determine the presence and abundance of bacteria from the Lactobacillus genus, measure the pH, and estimate the Nugent score. Drug safety evaluation was based on analysis of the types and occurrence of adverse events.

Results: Administration of inVag contributed to a significant decrease (between visits) in both vaginal pH (P<0.05) and Nugent score (P<0.05), and a significant increase in the abundance of Lactobacillus between visit I and visits III and IV (P<0.05). Molecular typing revealed the presence of Lactobacillus strains originating from inVag in 82% of women taking the drug at visit III, and 47.5% at visit IV. There was no serious adverse event related to inVag administration during the study.

Conclusion: The probiotic inVag is safe for administration to sustainably restore the healthy vaginal microbiota, as demonstrated by predominance of the Lactobacillus bacteria in vaginal microbiota.

Keywords: Lactobacillus; aerobic vaginitis; bacterial vaginosis; probiotics.

Figure 1

Flowchart of the clinical study. Note: ^aAs per protocol, a participant could be withdrawn from the clinical trial for more than one reason.

Figure 2

Changes in vaginal pH in patients receiving inVag^® or placebo at subsequent visits.

Figure 3

Changes in Nugent score in patients receiving inVag^® or placebo at subsequent visits.

Figure 4

Representative images of the improvement in vaginal vaginosis in one woman after vaginal application of inVag. Notes: Gram-stained preparations evaluated under 1,000× magnification according to the 10-point Nugent scale. (A) A vaginal specimen obtained at visit I assessed at six points in Nugent scale. (B) A vaginal specimen obtained on the third visit assessed at zero points in Nugent scale.

Figure 5

Comparison of changes in the abundance of L. fermentum, L. plantarum, and acidophilic Lactobacillus species in vaginal smears of patients receiving either inVag^® or placebo. Abbreviations: CFU, colony forming units; L. fermentum, Lactobacillus fermentum; L. plantarum, Lactobacillus plantarum.