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

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ClinicalTrials.gov Identifier: NCT02795845
Recruitment Status : Recruiting
First Posted : June 10, 2016
Last Update Posted : September 24, 2019
Sponsor:
Information provided by (Responsible Party):
HaEmek Medical Center, Israel

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.

Condition or disease Intervention/treatment Phase
Bacterial Vaginosis and Vaginal Candidiasis at Pregnancy Dietary Supplement: Probiotic Capsule containing L. acidophilus, L. Paracasei, L. Rhamnosus, streptococcus thermophilus and Bifidobacterium bifidum Other: Placebo Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 250 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Oral Probiotics for the Treatment and Prevention of Vulvovaginal Infections in Pregnancy - Double-blind, Randomized, Placebo-controlled Study
Actual Study Start Date : November 2016
Estimated Primary Completion Date : July 2021
Estimated Study Completion Date : September 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Primary prevention- probiotic capsules

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.

Dietary Supplement: Probiotic Capsule containing L. acidophilus, L. Paracasei, L. Rhamnosus, streptococcus thermophilus and Bifidobacterium bifidum
Probiotic

Placebo Comparator: Primary prevention - Placebo
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.
Other: Placebo
capsule without active ingredient

Experimental: Secondary prevention - 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 probiotic capsules.
Dietary Supplement: Probiotic Capsule containing L. acidophilus, L. Paracasei, L. Rhamnosus, streptococcus thermophilus and Bifidobacterium bifidum
Probiotic

Placebo Comparator: Secondary prevention - Placebo
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.
Other: Placebo
capsule without active ingredient




Primary Outcome Measures :
  1. The degree of vaginal lactobacilli colonization in the probiotic formula group versus placebo [ Time Frame: Around 4 months ]
    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.

  2. 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) ]
  3. 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 Measures :
  1. 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) ]
  2. The number of episodes of vaginal infections during pregnancy (either AVF/BV or VVC). [ Time Frame: From randomization until delivery (around 4 months) ]
  3. The rate of women, who suffer from obstetrical complications [ Time Frame: From randomization until delivery (around 4 months) ]
    preterm labor, intrauterine growth restriction (IUGR), PPROM, chorioamnionitis, post-partum fever, post-partum endometritis

  4. 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) ]
  5. Number of urinary tract infections during the study period [ Time Frame: From randomization until delivery (around 4 months) ]
  6. The rate of neonatal complications [ Time Frame: 30 days after delivery ]
    Neonatal acute respiratory distress syndrome, intraventricular hemorrhage, neonatal sepsis, admission to the neonatal intensive care unit

  7. 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) ]
  8. 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) ]
  9. 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) ]
  10. 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) ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02795845


Contacts
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Contact: ENAV YEFET, MD/PhD +972-4-6494516 enavy1@gmail.com

Locations
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Israel
Departement of obstetric and gynecology, HaEmek medical center Recruiting
Afula, Israel
Contact: Zohar Nachum, MD    +972-4-6494516    enavy1@gmail.com   
Women Helth center - Clalit Recruiting
Afula, Israel
Contact: Shlomo Betino, MD       battino@clalit.org.il   
Principal Investigator: Shlomo Betino, MD         
The holy family hospital Recruiting
Nazareth, Israel
Contact: Abeer Suliman, MD       abeersulim@gmail.com   
Principal Investigator: Abeer Suliman, MD         
Sponsors and Collaborators
HaEmek Medical Center, Israel
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Responsible Party: HaEmek Medical Center, Israel
ClinicalTrials.gov Identifier: NCT02795845    
Other Study ID Numbers: 0079-15
First Posted: June 10, 2016    Key Record Dates
Last Update Posted: September 24, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Additional relevant MeSH terms:
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Candidiasis
Vaginosis, Bacterial
Candidiasis, Vulvovaginal
Mycoses
Vaginal Diseases
Bacterial Infections
Vaginitis
Vulvovaginitis
Vulvitis
Vulvar Diseases