The Efficacy of Probiotics to Reduce Antepartum Group B Streptococcus Colonization.

• ClinicalTrials.gov Identifier: NCT03696953
• Recruitment Status: Active, not recruiting
• First Posted: October 5, 2018
• Last Update Posted: September 21, 2021
• Sponsor: Marquette University
• Collaborators: Aurora Health Care; University of Wisconsin, Madison
• Information provided by (Responsible Party): Marquette University

Study Description

Brief Summary:

This study is a randomized double blind, placebo controlled trial to determine the efficacy of an oral probiotic in reducing antenatal Group B Streptococcus colonization. The goal of this study is to demonstrate that women in the probiotics group will experience; (1) reduced GBS prenatal colonization at 36± 2 weeks gestation and lower levels of GBS colonization, (2) less need for intrapartum antibiotic prophylaxis and (3) fewer prenatal gastrointestinal symptoms compared to women in the placebo group.

Intrapartum measures were added and IRB approved in Feb 2020 as a pilot and feasiblity substudy. The goals of this study are as follows: (1) Explore the effect of antepartum exposure to Florajen3 on maternal and neonatal residual GBS and the maternal microbiome. We anticipate that (1)At the time of labor, more women in the probiotics group will test negative for GBS on vaginal to rectal swabs compared to those in the placebo group and (2) Fewer neonates born to women in the probiotic group will have GBS on nasal-oral pharynx cultures within several hours of birth compared to those born to neonates in the control group.

Condition or disease	Intervention/treatment	Phase
Group B Streptococcus Carrier in Childbirth; Gastrointestinal Symptoms	Biological: Florajen3	Phase 2

Detailed Description:

Group B streptococcus (GBS) is the most prevalent cause of perinatal infection, with mortality and profound comorbidities for neonates. Vaginal and gastrointestinal (GI) colonization with GBS occurs in up to 30% of adult women, with highest rates in African Americans. Pregnant women can pass GBS to their fetuses during vaginal birth, putting them at risk for Early Onset Group B Streptococcus Disease (EOGBSD), which is associated with a neonatal mortality rate of 5-10% and morbidity of approximately 50%. The Centers for Disease Control and Prevention (CDC) 2010 guidelines require universal antepartum GBS screening by vaginal to rectal cultures of all women at 35-37 weeks gestation, and intravenously administered intrapartum antibiotic prophylaxis (IAP) of two or more doses if a woman is found to be colonized with GBS. While use of these guidelines has significantly reduced EOGBSD incidence from 1.7 per 1,000 live births to 0.34-0.37, up to 30% of laboring women and their fetuses are exposed to IAP. Complications associated with IAP are significant for both the mother (increased incidence of antibiotic resistance, allergic sensitization, diarrhea including Clostridium difficile, and fungal infections) and neonate (gut dysbiosis, opportunistic infections, and allergic risk). The proposed study will test a low-cost, safe, innovative approach to reduce prenatal colonization with GBS, while adhering to CDC guidelines for EOGBSD prevention. Investigators hypothesize that women who ingest a commercially available oral probiotic combination product (Florajen3, containing Lactobacillus acidophilus, Bifidobacterium lactis, and Bifidobacterium longum) daily from 28 weeks gestation through the time of labor will have a lower risk of GBS colonization compared to women taking placebo. The purpose of this Phase 2 placebo-controlled, double blind, randomized controlled trial (RCT) is to determine the efficacy of once daily ingestion of Florajen3 by healthy low-risk pregnant women from 28 weeks gestation until the time of labor to (a) reduce the proportion of women with GBS colonization and thus (b) reduce the number of women who receive IAP. Investigators expect this intervention to alter the vaginal and rectal microbiota by (c) increasing Lactobacillus colony counts, (d) decreasing GBS colony counts, and (e) reducing GI symptoms. In preparation for this RCT, the research team conducted two preliminary studies (one in vitro, one in vivo), an integrative review of the literature regarding the use of prenatal probiotics, and a systematic review on probiotics and urogynecologic infections. The literature and preliminary work support the safety, tolerability, and potentially high impact of the oral probiotic as an innovative, low-risk, easy-to-use intervention to reduce GBS colonization during pregnancy and significantly reduce exposure of mothers and infants to IAP and the associated complications. If positive, findings from this study will shift the paradigm in clinical practice and be used to design and conduct a larger RCT to extend the science of nursing, midwifery, obstetrics, microbiology, clinical nutrition, and infectious disease for care of pregnant women and their infants.

Approximately 10% of women who tested negative for GBS at 36 weeks will become positive at the time of labor and birth. This "residual GBS" may be responsible for cases of EOGBSD cases.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 116 participants
• Allocation: Randomized
• Intervention Model: Factorial Assignment
• Intervention Model Description: Healthy pregnant participants will be randomly assigned to one of two groups (Probiotic vs Placebo) that are blind to participants and researchers. Both groups will take one capsule daily and have the same study measures at the same times.
• Masking: Triple (Participant, Care Provider, Investigator)
• Masking Description: Double Blind Randomized Placebo Controlled Trial.
• Primary Purpose: Prevention
• Official Title: The Efficacy of Probiotics to Reduce Antepartum Group B Streptococcus Colonization
• Actual Study Start Date: February 1, 2019
• Estimated Primary Completion Date: June 30, 2022
• Estimated Study Completion Date: December 30, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: Probiotic; Florajen3 Combination Probiotic Product 15 billion CFU per capsule 1 capsule daily from 28 weeks until the time of birth.	Biological: Florajen3; Probiotic combination product One capsule daily by mouth.
No Intervention: Placebo; Microcrystalline Cellulose

Outcome Measures

Primary Outcome Measures :

1. Proportion of participants with positive qualitative GBS culture [ Time Frame: 36 weeks gestation ]
   Qualitative

Secondary Outcome Measures :

1. GBS quantitive colony counts in colony forming units (CFU) [ Time Frame: 36 weeks gestation ]
   quantitative GBS colonization
2. Gastrointestinal (GI) symptom score [ Time Frame: 36 weeks gestation ]
   GI symptoms on Modified Severity of Dyspepsia non-pain symptom sub scale

Other Outcome Measures:

1. Maternal residual GBS [ Time Frame: On admission to labor and delivery ]
   Qualitative GBS (positive/negative) vaginal to rectal swab intrapartum
2. Neonatal GBS colonization [ Time Frame: 1-2 hours of life ]
   Qualitative GBS (positive/negative) oral/nasal swab

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Gender Based Eligibility: Yes
• Gender Eligibility Description: Pregnancy
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Healthy adult (≥ 18 years of age) pregnant women who are 28±2 weeks gestation at enrollment [calculated from the first day of Last Normal Menstrual Period (LNMP) and/or ultrasound (US)]
• With: No obstetric complication* (e.g., pre-eclampsia, gestational diabetes, multiple gestation)
• No fetal complication (e.g., birth defect, intrauterine growth restriction)
• No medical complication (e.g., hypertension, diabetes mellitus)
• Who do not currently ingest an over the counter probiotic supplement (not including yogurt)
• Who can both speak and read English
• Who regularly attend prenatal care (defined as not > 1 prior missed appointment during this pregnancy)
• No Hypersensitivity reaction to β-lactam antibiotics

Exclusion Criteria:

• Those less than 18 years of age
• Non-pregnant women
• Later in pregnancy than 30 weeks gestation at enrollment [per LNMP and/or US]
• Those with an obstetric, fetal or medical complication of pregnancy
• Pregnant women who have a history of GBS bacteriuria during the current pregnancy or have previously given birth to a GBS affected child
• Women who are currently ingesting an over the counter probiotic supplement (except for yogurt)
• Women who are planning an elective repeat cesarean birth
• Women who do not speak and read English
• Women with a history of missing more than one scheduled prenatal visit during this pregnancy
• Hypersensitivity reaction to β-lactam antibiotics

Contacts and Locations

Locations

United States, Wisconsin

Aurora Sinai Medical Center

Milwaukee, Wisconsin, United States, 53233

Sponsors and Collaborators

Marquette University

Aurora Health Care

University of Wisconsin, Madison

Investigators

• Principal Investigator: Lisa C Hanson, PhD; Marquette University, College of Nursing

More Information

Publications:

Hanson L, Vandevusse L, Duster M, Warrack S, Safdar N. Feasibility of oral prenatal probiotics against maternal group B Streptococcus vaginal and rectal colonization. J Obstet Gynecol Neonatal Nurs. 2014 May-Jun;43(3):294-304. doi: 10.1111/1552-6909.12308. Epub 2014 Apr 22.

Hanson L, VandeVusse L, Jermé M, Abad CL, Safdar N. Probiotics for Treatment and Prevention of Urogenital Infections in Women: A Systematic Review. J Midwifery Womens Health. 2016 May;61(3):339-55. doi: 10.1111/jmwh.12472. Review.

VandeVusse L, Hanson L, Safdar N. Perinatal outcomes of prenatal probiotic and prebiotic administration: an integrative review. J Perinat Neonatal Nurs. 2013 Oct-Dec;27(4):288-301; quiz E1-2. doi: 10.1097/JPN.0b013e3182a1e15d. Review.

Hanson L, Vandevusse L. Probiotics are food; herbs are plants; what's the risk? Informed consent for complementary and integrative therapies. J Perinat Neonatal Nurs. 2010 Jul-Sep;24(3):201-4. doi: 10.1097/JPN.0b013e3181e8f930. Review.

• Responsible Party: Marquette University
• ClinicalTrials.gov Identifier: NCT03696953
• Other Study ID Numbers: 1R21HD095320-01 ( U.S. NIH Grant/Contract )
• First Posted: October 5, 2018
• Last Update Posted: September 21, 2021
• Last Verified: September 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Marquette University:

Probiotics; Pregnancy; Group B Streptococcus; Gastrointestinal symptoms