Clinical trial NCT02795845: 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
Overall status: COMPLETED
Phase: NA
Conditions: Bacterial Vaginosis and Vaginal Candidiasis At Pregnancy
Lead sponsor: HaEmek Medical Center, Israel
Sponsor class: OTHER
First posted: 2016-06-10
Enrollment: 157
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: The degree of vaginal lactobacilli colonization in the probiotic formula group versus placebo
timeFrame: Around 4 months
measure: 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.
timeFrame: From date of randomization until the date of first documented episode or until delivery (around 4 months)
measure: 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.
timeFrame: Until delivery (around 4 months)
Secondary outcomes:
measure: Duration of time from the beginning of the study until an episode of vaginal infection (either AVF/BV or VVC).
timeFrame: From randomization until delivery (around 4 months)
measure: The number of episodes of vaginal infections during pregnancy (either AVF/BV or VVC).
timeFrame: From randomization until delivery (around 4 months)
measure: The rate of women, who suffer from obstetrical complications
timeFrame: From randomization until delivery (around 4 months)
measure: The rate and type of adverse effects in the probiotic versus placebo groups (e.g gastrointestinal symptoms).
timeFrame: From randomization until two weeks after delivery (around 4 months)
measure: Number of urinary tract infections during the study period
timeFrame: From randomization until delivery (around 4 months)
measure: The rate of neonatal complications
timeFrame: 30 days after delivery
measure: 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.
timeFrame: From randomization until delivery (around 4 months)
measure: 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.
timeFrame: From randomization until delivery (around 4 months)
measure: 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.
timeFrame: From randomization until delivery (around 4 months)
measure: 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.
timeFrame: From randomization until delivery (around 4 months)
Other outcomes:
Locations:
city: Afula
country: Israel
facility: Departement of obstetric and gynecology, HaEmek medical center
city: Afula
country: Israel
facility: Women Helth center - Clalit
city: Nazareth
country: Israel
facility: The holy family hospital
Study officials:
References: