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

Tomusiak A, Strus M, Heczko PB, Adamski P, Stefański G, Mikołajczyk-Cichońska A, Suda-Szczurek M - Drug Des Devel Ther (2015)

Bottom Line: Drug safety evaluation was based on analysis of the types and occurrence of adverse events.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology, Jagiellonian University Medical College, Kraków, Poland.

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.

No MeSH data available.


Related in: MedlinePlus

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.
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f4-dddt-9-5345: 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.

Mentions: The efficacy analysis based on 112 participants was based on vaginal pH, microbiological Nugent score, and degree and persistence of vaginal colonization by at least one of Lactobacillus strains from the active product. Statistical analysis of the data revealed the following four main results: First, the group of women that received the probiotic experienced a significant reduction of vaginal pH between visits I and III – from 5.03 to 4.71 (P<0.0016) and between visits I and IV – from 5.03 to 4.66 (P<0.0001). A gradual decrease in vaginal pH was also seen in the placebo group; however, the change over time was not significant (Figure 2). Second, administration of the probiotic preparation resulted in a significant decrease in Nugent score between visit I and visits III – from 2.12 to 1.25 (P=0.0001) and IV – from 2.12 to 0.9 (P<0.0001). Additionally, the Nugent score decreased significantly between visits III and IV from 1.25 to 0.9 (P=0.0238), which occurred approximately 14 days after cessation of inVag treatment. This suggests that a 7-day treatment cycle with inVag results in significant improvement of the vaginal microflora. The Nugent score also decreased significantly between visit I and visits III (P<0.0001) and IV (P=0.0002), in women who received placebo, but this group did not show the continuous decrease between visits III and IV (Figure 3). Changes in the vaginal microflora in women who used the probiotic preparation (according to Nugent score) are shown in Figure 4. Third, women who used the active product had a significant increase of the abundance of L. plantarum and L. fermentum in their vaginal microbiota. These species increased approximately 1,000 times over the 7 days (on average) after completion of the treatment (visit III), and then they slowly declined over the subsequent 8 days until visit IV. In patients who received the placebo, the abundance of L. plantarum and L. fermentum increased much more slowly than in patients who received the probiotic product. In this group, numbers of these strains only increased by ~10 times by the fourth visit. The change in abundance of L. acidophilus and L. gasseri was similar in both treatment groups (Figure 5). Finally, the degree and sustainability of vaginal colonization by at least one Lactobacillus strain from the active product, based on molecular typing tests, confirmed colonization of the vaginal epithelium by L. fermentum 57A, L. plantarum 57B, and L. gasseri 57C in 82% of women who received the probiotic on visit III and 47.5% on visit IV.


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

Tomusiak A, Strus M, Heczko PB, Adamski P, Stefański G, Mikołajczyk-Cichońska A, Suda-Szczurek M - Drug Des Devel Ther (2015)

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.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4590344&req=5

f4-dddt-9-5345: 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.
Mentions: The efficacy analysis based on 112 participants was based on vaginal pH, microbiological Nugent score, and degree and persistence of vaginal colonization by at least one of Lactobacillus strains from the active product. Statistical analysis of the data revealed the following four main results: First, the group of women that received the probiotic experienced a significant reduction of vaginal pH between visits I and III – from 5.03 to 4.71 (P<0.0016) and between visits I and IV – from 5.03 to 4.66 (P<0.0001). A gradual decrease in vaginal pH was also seen in the placebo group; however, the change over time was not significant (Figure 2). Second, administration of the probiotic preparation resulted in a significant decrease in Nugent score between visit I and visits III – from 2.12 to 1.25 (P=0.0001) and IV – from 2.12 to 0.9 (P<0.0001). Additionally, the Nugent score decreased significantly between visits III and IV from 1.25 to 0.9 (P=0.0238), which occurred approximately 14 days after cessation of inVag treatment. This suggests that a 7-day treatment cycle with inVag results in significant improvement of the vaginal microflora. The Nugent score also decreased significantly between visit I and visits III (P<0.0001) and IV (P=0.0002), in women who received placebo, but this group did not show the continuous decrease between visits III and IV (Figure 3). Changes in the vaginal microflora in women who used the probiotic preparation (according to Nugent score) are shown in Figure 4. Third, women who used the active product had a significant increase of the abundance of L. plantarum and L. fermentum in their vaginal microbiota. These species increased approximately 1,000 times over the 7 days (on average) after completion of the treatment (visit III), and then they slowly declined over the subsequent 8 days until visit IV. In patients who received the placebo, the abundance of L. plantarum and L. fermentum increased much more slowly than in patients who received the probiotic product. In this group, numbers of these strains only increased by ~10 times by the fourth visit. The change in abundance of L. acidophilus and L. gasseri was similar in both treatment groups (Figure 5). Finally, the degree and sustainability of vaginal colonization by at least one Lactobacillus strain from the active product, based on molecular typing tests, confirmed colonization of the vaginal epithelium by L. fermentum 57A, L. plantarum 57B, and L. gasseri 57C in 82% of women who received the probiotic on visit III and 47.5% on visit IV.

Bottom Line: Drug safety evaluation was based on analysis of the types and occurrence of adverse events.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology, Jagiellonian University Medical College, Kraków, Poland.

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.

No MeSH data available.


Related in: MedlinePlus