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Oral Probiotics for the Treatment and Prevention of Vulvovaginal Infections in Pregnancy - Double-blind, Randomized, Placebo-controlled Study

Primary Purpose

Bacterial Vaginosis and Vaginal Candidiasis at Pregnancy

Status
Completed
Phase
Not Applicable
Locations
Israel
Study Type
Interventional
Intervention
Probiotic Capsule containing L. acidophilus, L. Paracasei, L. Rhamnosus, streptococcus thermophilus and Bifidobacterium bifidum
Placebo
Sponsored by
HaEmek Medical Center, Israel
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Bacterial Vaginosis and Vaginal Candidiasis at Pregnancy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleAccepts Healthy Volunteers

Inclusion criteria:

  1. Women who will report on vaginal discharge or signs/symptoms consistent with vaginal/vulvar infection
  2. Above 18 years old
  3. pregnant women until 30th weeks of gestation
  4. Willing to participate and singed on consent form

Exclusion criteria:

  1. Patient refuse to participate in the study
  2. Women with preterm premature rupture of the membranes (at enrollment)
  3. Immunocompromised women (e.g. autoimmune diseases treated medically)
  4. Failure to eradicate BV/AVF and/or VVC after 2 treatment cycles
  5. Trichomonas infection at enrollment
  6. Allergy to Soy (The capsules are manufactured in same line as Soy and fish therefore may contain those allergens)
  7. Allergy to Fish (The capsules are manufactured in same line as Soy and fish therefore may contain those allergens)
  8. Women who take probiotic treatment orally or vaginally that refuse to discontinue treatment.
  9. Vaginal swab result suitable for study arm in which enrollment was completed

Sites / Locations

  • Departement of obstetric and gynecology, HaEmek medical center
  • Women Helth center - Clalit
  • The holy family hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Arm Label

Primary prevention- probiotic capsules

Primary prevention - Placebo

Secondary prevention - probiotic capsules

Secondary prevention - Placebo

Arm Description

patients with normal vaginal flora in the experimental arm will be treated with Probiotic capsules (containing L. acidophilus, L. Paracasei, L. Rhamnosus, streptococcus thermophilus, Bifidobacterium bifidum and B. Lactis). one capsule twice a day until delivery.

patients with normal vaginal flora in the placebo arm will be treated with a capsule without active ingredient, one capsule twice a day until delivery.

Patients with abnormal vaginal flora/bacterial vaginosis or vaginal candidiasis in the experimental arm will be treated with antibiotic (either clindamycin, metronidazole or both if necessary) or antimycotic treatment. Once the infection was eradicated, the patient will be given probiotic capsules.

Patients with abnormal vaginal flora/bacterial vaginosis or vaginal candidiasis in the experimental arm will be treated with antibiotic (either clindamycin, metronidazole or both if necessary) or antimycotic treatment. Once the infection was eradicated, the patient will be given placebo without active ingredient.

Outcomes

Primary Outcome Measures

The degree of vaginal lactobacilli colonization in the probiotic formula group versus placebo
Lactobacilli culture will be made from a vaginal specimen. The pattern of bacterial growth will be used for a semi-quantitative interpretation in a scale of 0-no vaginal colonization to 4-substantial colonization.
The rate of women in the primary prevention group, who developed any vaginal infection (BV/AVF/VVC) during the study period until delivery in the probiotic formula group versus placebo.
The rate of women in the second prevention group who developed any vaginal infection (BV/AVF/VVC) during the study period until delivery in the probiotic formula group versus placebo.

Secondary Outcome Measures

Duration of time from the beginning of the study until an episode of vaginal infection (either AVF/BV or VVC).
The number of episodes of vaginal infections during pregnancy (either AVF/BV or VVC).
The rate of women, who suffer from obstetrical complications
preterm labor, intrauterine growth restriction (IUGR), PPROM, chorioamnionitis, post-partum fever, post-partum endometritis
The rate and type of adverse effects in the probiotic versus placebo groups (e.g gastrointestinal symptoms).
Number of urinary tract infections during the study period
The rate of neonatal complications
Neonatal acute respiratory distress syndrome, intraventricular hemorrhage, neonatal sepsis, admission to the neonatal intensive care unit
The rate of women in the primary prevention group who developed AVF/BV during the study period until delivery in the probiotic formula group versus placebo.
The rate of women in the primary prevention group who developed VVC during the study period until delivery in the probiotic formula group versus placebo.
The rate of women in the second prevention group who developed AVF/BV during the study period until delivery in the probiotic formula group versus placebo.
The rate of women in the second prevention group who developed VVC during the study period until delivery in the probiotic formula group versus placebo.

Full Information

First Posted
June 7, 2016
Last Updated
August 2, 2021
Sponsor
HaEmek Medical Center, Israel
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1. Study Identification

Unique Protocol Identification Number
NCT02795845
Brief Title
Oral Probiotics for the Treatment and Prevention of Vulvovaginal Infections in Pregnancy - Double-blind, Randomized, Placebo-controlled Study
Official Title
Oral Probiotics for the Treatment and Prevention of Vulvovaginal Infections in Pregnancy - Double-blind, Randomized, Placebo-controlled Study
Study Type
Interventional

2. Study Status

Record Verification Date
August 2021
Overall Recruitment Status
Completed
Study Start Date
November 2016 (Actual)
Primary Completion Date
July 2021 (Actual)
Study Completion Date
August 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
HaEmek Medical Center, Israel

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
During pregnancy, bacterial vaginosis (BV), abnormal vaginal flora (AVF) and vulvovaginal candidiasis (VVC) are associated with serious complications and discomfort. Yet, treatment options are limited. Lactobacilli administration was suggested to treat and prevent vaginal infections. However, this has not been examined in pregnant women, the information regarding oral treatment is scarce, and the mechanisms in which oral ingestion of probiotics induce vaginal lactobacilli proliferation are not well established. In the present study we will examine if oral probiotics are effective in prevention of vaginal infections by migration of lactobacilli from the digestive system to the vagina in pregnant women.
Detailed Description
During pregnancy, bacterial vaginosis (BV), abnormal vaginal flora (AVF) and vulvovaginal candidiasis (VVC) are associated with serious complications and discomfort. Yet, treatment options are limited. Lactobacilli administration was suggested to treat and prevent vaginal infections. However, this has not been examined in pregnant women, the information regarding oral treatment is scarce, and the mechanisms in which oral ingestion of probiotics induce vaginal lactobacilli proliferation are not well established. Working hypothesis: Oral probiotics will be effective in prevention of vaginal infections by migration of lactobacilli from the digestive system to the vagina in pregnant women. Type of research and methods of data collection: randomized placebo-controlled trial. Pregnant patients with symptoms consisted with vaginal infection will be examined and vaginal smear will be obtained, according to which the patients will be allocated to the following groups: Primary prevention - women with normal vaginal flora Secondary prevention - women positive for AVF/BV and/or VVC- those women will be treated with antibiotic and/or antimycotic treatment. Following treatment, another smear will be taken to confirm infection eradication. If infection is still present, additional antibiotic and/or antimycotic treatment will be administered after which additional smear will be taken. Women with normal vaginal flora (after one of two treatments) will be recruited for the secondary prevention group. In each group the patients will be divided into two subgroups, which will receive one capsule twice a day of either the Probiotic Femina ׀׀ capsules or placebo. At the initial examination and once a month all the study groups will be tested for the presence of AVF/BV and candida. Additional vaginal samples will be taken to evaluate the presence of lactobacilli from the capsule and semi-quantitative assessment of vaginal lactobacilli.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Bacterial Vaginosis and Vaginal Candidiasis at Pregnancy

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
157 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Primary prevention- probiotic capsules
Arm Type
Experimental
Arm Description
patients with normal vaginal flora in the experimental arm will be treated with Probiotic capsules (containing L. acidophilus, L. Paracasei, L. Rhamnosus, streptococcus thermophilus, Bifidobacterium bifidum and B. Lactis). one capsule twice a day until delivery.
Arm Title
Primary prevention - Placebo
Arm Type
Placebo Comparator
Arm Description
patients with normal vaginal flora in the placebo arm will be treated with a capsule without active ingredient, one capsule twice a day until delivery.
Arm Title
Secondary prevention - probiotic capsules
Arm Type
Experimental
Arm Description
Patients with abnormal vaginal flora/bacterial vaginosis or vaginal candidiasis in the experimental arm will be treated with antibiotic (either clindamycin, metronidazole or both if necessary) or antimycotic treatment. Once the infection was eradicated, the patient will be given probiotic capsules.
Arm Title
Secondary prevention - Placebo
Arm Type
Placebo Comparator
Arm Description
Patients with abnormal vaginal flora/bacterial vaginosis or vaginal candidiasis in the experimental arm will be treated with antibiotic (either clindamycin, metronidazole or both if necessary) or antimycotic treatment. Once the infection was eradicated, the patient will be given placebo without active ingredient.
Intervention Type
Dietary Supplement
Intervention Name(s)
Probiotic Capsule containing L. acidophilus, L. Paracasei, L. Rhamnosus, streptococcus thermophilus and Bifidobacterium bifidum
Intervention Description
Probiotic
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
capsule without active ingredient
Primary Outcome Measure Information:
Title
The degree of vaginal lactobacilli colonization in the probiotic formula group versus placebo
Description
Lactobacilli culture will be made from a vaginal specimen. The pattern of bacterial growth will be used for a semi-quantitative interpretation in a scale of 0-no vaginal colonization to 4-substantial colonization.
Time Frame
Around 4 months
Title
The rate of women in the primary prevention group, who developed any vaginal infection (BV/AVF/VVC) during the study period until delivery in the probiotic formula group versus placebo.
Time Frame
From date of randomization until the date of first documented episode or until delivery (around 4 months)
Title
The rate of women in the second prevention group who developed any vaginal infection (BV/AVF/VVC) during the study period until delivery in the probiotic formula group versus placebo.
Time Frame
Until delivery (around 4 months)
Secondary Outcome Measure Information:
Title
Duration of time from the beginning of the study until an episode of vaginal infection (either AVF/BV or VVC).
Time Frame
From randomization until delivery (around 4 months)
Title
The number of episodes of vaginal infections during pregnancy (either AVF/BV or VVC).
Time Frame
From randomization until delivery (around 4 months)
Title
The rate of women, who suffer from obstetrical complications
Description
preterm labor, intrauterine growth restriction (IUGR), PPROM, chorioamnionitis, post-partum fever, post-partum endometritis
Time Frame
From randomization until delivery (around 4 months)
Title
The rate and type of adverse effects in the probiotic versus placebo groups (e.g gastrointestinal symptoms).
Time Frame
From randomization until two weeks after delivery (around 4 months)
Title
Number of urinary tract infections during the study period
Time Frame
From randomization until delivery (around 4 months)
Title
The rate of neonatal complications
Description
Neonatal acute respiratory distress syndrome, intraventricular hemorrhage, neonatal sepsis, admission to the neonatal intensive care unit
Time Frame
30 days after delivery
Title
The rate of women in the primary prevention group who developed AVF/BV during the study period until delivery in the probiotic formula group versus placebo.
Time Frame
From randomization until delivery (around 4 months)
Title
The rate of women in the primary prevention group who developed VVC during the study period until delivery in the probiotic formula group versus placebo.
Time Frame
From randomization until delivery (around 4 months)
Title
The rate of women in the second prevention group who developed AVF/BV during the study period until delivery in the probiotic formula group versus placebo.
Time Frame
From randomization until delivery (around 4 months)
Title
The rate of women in the second prevention group who developed VVC during the study period until delivery in the probiotic formula group versus placebo.
Time Frame
From randomization until delivery (around 4 months)

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion criteria: Women who will report on vaginal discharge or signs/symptoms consistent with vaginal/vulvar infection Above 18 years old pregnant women until 30th weeks of gestation Willing to participate and singed on consent form Exclusion criteria: Patient refuse to participate in the study Women with preterm premature rupture of the membranes (at enrollment) Immunocompromised women (e.g. autoimmune diseases treated medically) Failure to eradicate BV/AVF and/or VVC after 2 treatment cycles Trichomonas infection at enrollment Allergy to Soy (The capsules are manufactured in same line as Soy and fish therefore may contain those allergens) Allergy to Fish (The capsules are manufactured in same line as Soy and fish therefore may contain those allergens) Women who take probiotic treatment orally or vaginally that refuse to discontinue treatment. Vaginal swab result suitable for study arm in which enrollment was completed
Facility Information:
Facility Name
Departement of obstetric and gynecology, HaEmek medical center
City
Afula
Country
Israel
Facility Name
Women Helth center - Clalit
City
Afula
Country
Israel
Facility Name
The holy family hospital
City
Nazareth
Country
Israel

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Oral Probiotics for the Treatment and Prevention of Vulvovaginal Infections in Pregnancy - Double-blind, Randomized, Placebo-controlled Study

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