The Association Between the Transfer of Lactobacilli From the Gastrointestinal Tract to the Vagina and the Prevention / Eradication of Abnormal Vaginal Flora in High Risk Pregnancies

Pregnant women at high risk for preterm labor from at least 13 weeks of gestation will be tested to detect abnormal vaginal flora (AVF) or its severe form - bacterial vaginosis (BV) by taking vaginal smear. Treatment will be given according to the results.

Study Overview

• Status: Terminated
• Conditions: Pregnancy
• Intervention / Treatment: Other: Placebo; Dietary supplement: Urex Plus; Dietary supplement: Probotic capsule containing L. rhamnosus GR-1and L. reuteri RC-14

Detailed Description

Pregnant women at high risk for preterm labor from at least 13 weeks of gestation will be tested to detect AVF/BV by taking vaginal smear. Diagnosis will be according to the Nugent score criteria. Treatment will be given according to the results:

Patient with a positive smear for AVF- patients tested positive will be treated with either clindamycin or metronidazole. Following treatment another smear will be taken according to which the patients will be divided into 2 research groups: (1) Assessing the effectiveness of probiotic formula to prevent AVF re-infection (secondary infection) - this group includes patients with normal vaginal flora following antibiotic administration. (2) Assessing the effectiveness of probiotic formula to eradicate AVF - this group includes patients with persistent AVF following antibiotic administration (first and second line). In each group the patients will be divided into a research group which will receive the probiotic formula UREX PLUS (containing L. rhamnosus GR-1and L. reuteri RC-14) and a control group which will receive a placebo twice a day until 36.6 weeks of gestation.

Patient with a negative smear for AVF - in those patients the effectiveness of probiotic formula will be tested for primary prevention. These patients will be divided into a research group which will receive the probiotic formula UREX PLUS and a control group which will receive a placebo twice a day until 36.6 weeks of gestation.

Finally, the colonization of lactobacilli in the vaginal flora will be examined by dividing patients with normal vaginal flora into one group receiving a probiotic capsule containing L. rhamnosus GR-1 and L. reuteri RC-14 twice a day for 2 months and a second group without intervention. After two months the group receiving probiotic capsule will receive no treatment and the second group will receive probiotic capsule containing L. rhamnosus GR-1and L. reuteri RC-14 twice a day for 2 months.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Israel
  • Afula, Israel
    • Haemek Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• pregnant women from at least 13 weeks of gestation with a risk factor for preterm labor

Exclusion Criteria:

• Women with preterm premature rupture of the membranes
• Immunocompromised women
• Planned elective preterm birth for reasons other than preterm premature rupture of membranes

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Primary prevention - Urex Plus; Patients with Normal vaginal flora in the experimental arm will be treated with UREX PLUS	Dietary supplement: Urex Plus; Probiotic
Placebo Comparator: Primary prevention - Placebo; Patients with Normal vaginal flora in the Placebo arm will be treated with a capsule without active ingredient	Other: Placebo; capsule without active ingredient
Experimental: Secondary prevention - Urex Plus; Patients with abnormal vaginal flora in the experimental arm will be treated with antibiotic (either clindamycin, metronidazole or both if one was not effective), Once AVF/BV was eradicated, the patient will be given UREX PLUS	Dietary supplement: Urex Plus; Probiotic
Placebo Comparator: Secondary prevention - Placebo; Patients with abnormal vaginal flora in the Placebo arm will be treated with antibiotic (either clindamycin, metronidazole or both if one was not effective), Once AVF/BV was eradicated, the patient will be given placebo without active ingredient	Other: Placebo; capsule without active ingredient
Experimental: Eradication - Urex Plus; Patients with persistent abnormal vaginal flora following treatment with clindamycin and metronidazole in the experimental arm will be treated with UREX PLUS	Dietary supplement: Urex Plus; Probiotic
Placebo Comparator: Eradication - Placebo; Patients with persistent abnormal vaginal flora following treatment with clindamycin and metronidazole in the placebo arm will be treated with placebo without active ingredient	Other: Placebo; capsule without active ingredient
Other: Lactobacilli transfer - probiotic capsule; Patients with Normal vaginal flora will be treated with a probotic capsule containing L. rhamnosus GR-1and L. reuteri RC-14 for two months afterwhich they will receive no treatment for additional two months. Lactobacili colonization in the vaginal flora will be tested	Dietary supplement: Probotic capsule containing L. rhamnosus GR-1and L. reuteri RC-14
Other: Lactobacilli transfer - probiotic capsule after 2 months; Patients with Normal vaginal flora will be followed for two months without intervention afterwhich they will receive a probotic capsule containing L. rhamnosus GR-1and L. reuteri RC-14 for two months. Lactobacili colonization in the vaginal flora will be tested.	Dietary supplement: Probotic capsule containing L. rhamnosus GR-1and L. reuteri RC-14

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The amount of lactobacilli in the vaginal	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.	once a month until week 36.6 of labor
The rate of women with normal vaginal flora at enrollment, who developed AVF/BV during the study period		From date of randomization until the date of first documented episode or until delivery (around 4 months)
The rate of women with AVF/BV at enrollment whose infection was eradicated following antibiotics, who developed AVF/BV during the study period		From date of randomization until the date of first documented episode or until delivery (around 4 months)
The rate of women with AVF/BV at enrollment whose infection was not eradicated following antibiotics, who restored the normal vaginal flora during the study period		Until delivery (around 4 months)

Secondary Outcome Measures

Outcome Measure	Time Frame
Duration of time from the beginning of the study until an episode of AVF/BV	From date of randomization until the date of first documented episode or until delivery (around 4 months)
The number of episodes of BV/AVF during pregnancy	Until delivery (around 4 months)
The rate of women, who suffer from obstetrical outcomes(preterm labor, intrauterine growth restriction, preterm premature rupture of membranes, chorioamnionitis, post-partum fever, post-partum endometritis, neonatal sepsis and neonatal complications)	Until delivery (around 4 months)
The rate and type of adverse effects in the probiotic versus placebo groups	Until delivery (around 4 months)
Number of urinary tract infections during the study period	Until delivery (around 4 months)

Collaborators and Investigators

• Sponsor: HaEmek Medical Center, Israel
• Investigators: Principal Investigator: ENAV YEFET, MD/PhD, HaEmek Medical Center , Afula

Study record dates

Study Major Dates

• Study Start: January 1, 2016
• Primary Completion (Actual): March 14, 2017
• Study Completion (Actual): January 10, 2019

Study Registration Dates

• First Submitted: April 20, 2015
• First Submitted That Met QC Criteria: April 25, 2015
• First Posted (Estimate): April 30, 2015

Study Record Updates

• Last Update Posted (Actual): December 17, 2019
• Last Update Submitted That Met QC Criteria: December 15, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Other Study ID Numbers: 0096-13