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Clinical Trials/NCT03407157
NCT03407157Active, not recruitingPhase 3

Oral Probiotic Supplementation in Pregnancy to Reduce Group B Streptococcus Colonization

University of British Columbia2 sites in 1 country168 target enrollmentStarted: January 16, 2020Last updated:
Conditions
Interventions

Trial Snapshot

Phase
Phase 3
Status
Active, not recruiting
Enrollment
168
Locations
2
Primary Endpoint
The primary outcome will be vaginal/rectal GBS colonization status at delivery

Study Overview

Brief Summary

This is a double-blind randomized placebo controlled trial that will investigate whether the use of three specific species of probiotics taken orally in pregnancy from 25 weeks gestation will reduce the incidence of Group B Streptococcus (GBS) colonization. Participants will take 2 capsules and 1 lozenge per day of either probiotic or placebo from 25 weeks gestation. The primary outcome will be the study-specific vaginal/rectal swab collected after 35 weeks gestation and before delivery. A reduction in women testing positive for GBS would lead to a decrease risk to infants of GBS infection and a reduction in the use of antibiotics leading to less maternal and neonatal antibiotic exposure.

Detailed Description

Background:

Group B streptococcus (GBS) infection of the newborn is a leading cause of neonatal morbidity and mortality in North America. Up to 30% of pregnant women are colonized with GBS. Half of the babies born to colonized mothers will become colonized themselves, and of those, about 1-2% may develop early onset GBS infection (EOGBS), which is associated with significant mortality (between 5% and 20%) and morbidity (71% bacteremia, 11% meningitis, 19% pneumonia). The current recommendation is for routine administration of IPA to women who test positive for GBS at term. Although IPA therapy may reduce the incidence of neonatal GBS infection, it can increase the risk of other infections such as E. Coli, neonatal thrush, and ampicillin resistant Enterobacteriaceae.

There is also accumulating evidence linking antibiotics in pregnancy with childhood asthma, childhood obesity, and obesity in later life. IPA is also associated with antibiotic resistance, diarrhoea (including Clostridium difficile), and fungal infections. There is a growing worldwide interest in utilizing probiotics to enhance and manipulate the human microbiome in order to reduce a wide range of communicable and non-communicable diseases. Probiotics have been studied extensively in pregnant women and are considered safe and well tolerated when ingested or used vaginally.

Probiotics in pregnancy may reduce GBS colonization and the need for intrapartum antibiotic prophylaxis through a number of mechanisms. Some probiotics produce antibacterial substances and film-like barriers to pathogens. By adhering to vaginal epithelial cells, probiotics also displace pathogens such as GBS. S. salivarius K12 has been shown to inhibit several GBS strains, including disease-implicated isolates from newborns and colonizing isolates from the vaginal tract of pregnant women. In vivo and in vitro studies demonstrate its ability to adhere to the vaginal epithelium and directly impair the growth and adherence of GBS.

Several pilot randomized trials of L. reuteri and L. rhamnosus show promise in their their ability to reduce GBS colonization and have been shown to be safe. In vivo and in vitro studies of various lactobacillus strains, including rhamnosus and reuteri, have demonstrated an inhibitory effect on GBS.

Study Design

Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel
Primary Purpose
Prevention
Masking
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description

The randomisation process will assign each participant with a unique study ID number. This study ID number will be required when allocating study drug bottles and lozenge packages and for recording data on the case report form (CRF). The drug bottle number and lozenge packs will be dispensed by a study team member directly to the participant. Probiotics and placebos will look and taste identical and drug bottles and lozenge packs and labels will look identical.

Eligibility Criteria

Ages
18 Years to 55 Years (Adult)
Sex
Female
Accepts Healthy Volunteers
Yes

Inclusion Criteria

  • Pregnant with a singleton
  • Gestational age between 23 and 25+0 weeks
  • Over the age of 18
  • Registered for delivery, at one of the participating centres
  • Under the care of a regulated maternity care provider (midwife, obstetrician (OB), or family physician).

Exclusion Criteria

  • Unable to provide consent
  • Fetus has known major anomalies
  • Significant immunosuppression
  • Type I or Type II diabetes (non-gestational)
  • Previous infant with GBS (these women will automatically be advised to be treated with IV antibiotic therapy)
  • GBS bacteriuria diagnosed in present pregnancy (reasoning as per above)
  • Plans to use oral or vaginal probiotic supplementation/therapy (capsules/tablets/lozenges/drinks) during their pregnancy (outside of natural food sources; yogurt, kimchi, kombucha etc)
  • Enrolled in another study that involves the administration of a drug/product

Arms & Interventions

Intervention

Experimental

Probiotic supplementation

Intervention: Probiotic supplementation (Dietary Supplement)

Control

Placebo Comparator

Placebo

Intervention: Placebo (Other)

Outcomes

Primary Outcomes

The primary outcome will be vaginal/rectal GBS colonization status at delivery

Time Frame: Last vaginal/rectal swab taken after 35 weeks gestation and prior to delivery

Measured using the study-specific rectal/vaginal swab

Secondary Outcomes

  • Maternal urinary tract infections(Questionnaires administered at intake (22-25 weeks), mid-term (29-33 weeks), term (35-37 weeks) and chart review (6 weeks post-birth))
  • Maternal vaginal candida infections(Questionnaires administered at intake (22-25 weeks), mid-term (29-33 weeks), term (35-37 weeks) and chart review (4-6 weeks postpartum))
  • Maternal antibiotic exposure(Questionnaires administered at intake (22-25 weeks), mid-term (29-33 weeks), term (35-37 weeks) and chart review (6 weeks post-birth))
  • Maternal bacterial vaginosis infections(Questionnaires administered at intake (22-25 weeks), mid-term (29-33 weeks), term (35-37 weeks) and chart review (6 weeks post-birth))

Investigators

Sponsor Class
Other
Responsible Party
Principal Investigator
Principal Investigator

Michelle Butler

Principal Investigator

University of British Columbia

Study Sites (2)

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