Oral Probiotic Supplementation in Pregnancy to Reduce Group B Streptococcus Colonization

NCT03407157 | Unknown Phase 3 DMC

• 1 other identifier: H17-02189
• Study Type: interventional
• Target: 168
• Locations: 1 country
• Sites: 2

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.

Conditions

Group B Streptococcus Carrier in Childbirth

Keywords

Probiotics; Pregnancy; GBS; Group B Streptococcus

Outcome Measures

Primary Outcomes (1)

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

  Measured using the study-specific rectal/vaginal swab

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

Secondary Outcomes (4)

• 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 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 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)

• 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)

Other Outcomes (13)

• Passage of probiotic strains to gastrointestinal tract and vaginal epithelium and adherence

  Oral and vaginal/rectal swabs taken at 23-25 weeks, 29-33 weeks, and 35 weeks

• Adverse events

  From the time of randomisation to 28 days of discontinuing the study supplements

• Gestational diabetes

  Number of Participants with gestational diabetes recorded in chart review at 4-6 weeks postpartum

Study Arms (2)

Intervention

EXPERIMENTAL

Probiotic supplementation

Dietary Supplement: Probiotic supplementation

Control

PLACEBO COMPARATOR

Placebo

Other: Placebo

Interventions

Probiotic supplementation DIETARY_SUPPLEMENT

Participants will take two capsules daily of Urex Plus VCap-5 (each containing 2.5 billion CFUs of L. rhamnosus and L. reuteri) and one lozenge of Blis K12 (1 billion CFUs of streptococcus Salivarius)

Intervention

Placebo OTHER

Participants will be asked to take 2 placebo capsules and 1 placebo lozenge daily from 25 weeks pregnancy

Control

Eligibility Criteria

• Age: 18 Years - 55 Years
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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).

You may not qualify if:

• 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

Sponsors & Collaborators

• University of British Columbia: lead
• Dublin City University: collaborator

Study Sites (2)

BC Women's Hospital

Vancouver, British Columbia, V6H 3N1, Canada

Location

St. Paul's Hospital

Vancouver, British Columbia, V6Z 1Y6, Canada

Location

Related Publications (22)

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  PMID: 18381532 BACKGROUND

• Cox LM, Blaser MJ. Antibiotics in early life and obesity. Nat Rev Endocrinol. 2015 Mar;11(3):182-90. doi: 10.1038/nrendo.2014.210. Epub 2014 Dec 9.

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• de Vrese M. Health benefits of probiotics and prebiotics in women. Menopause Int. 2009 Mar;15(1):35-40. doi: 10.1258/mi.2009.009008.

  PMID: 19237621 BACKGROUND

• Glasgow TS, Young PC, Wallin J, Kwok C, Stoddard G, Firth S, Samore M, Byington CL. Association of intrapartum antibiotic exposure and late-onset serious bacterial infections in infants. Pediatrics. 2005 Sep;116(3):696-702. doi: 10.1542/peds.2004-2421.

  PMID: 16140710 BACKGROUND

• 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.

  PMID: 24754328 BACKGROUND

• Elias J, Bozzo P, Einarson A. Are probiotics safe for use during pregnancy and lactation? Can Fam Physician. 2011 Mar;57(3):299-301.

  PMID: 21402964 BACKGROUND

• Money D, Allen VM; INFECTIOUS DISEASES COMMITTEE. The prevention of early-onset neonatal group B streptococcal disease. J Obstet Gynaecol Can. 2013 Oct;35(10):939-948. doi: 10.1016/S1701-2163(15)30818-5.

  PMID: 24165063 BACKGROUND

• Mueller NT, Whyatt R, Hoepner L, Oberfield S, Dominguez-Bello MG, Widen EM, Hassoun A, Perera F, Rundle A. Prenatal exposure to antibiotics, cesarean section and risk of childhood obesity. Int J Obes (Lond). 2015 Apr;39(4):665-70. doi: 10.1038/ijo.2014.180. Epub 2014 Oct 9.

  PMID: 25298276 BACKGROUND

• Ohlsson A, Shah VS. Intrapartum antibiotics for known maternal Group B streptococcal colonization. Cochrane Database Syst Rev. 2013 Jan 31;(1):CD007467. doi: 10.1002/14651858.CD007467.pub3.

  PMID: 23440815 BACKGROUND

• PHAC (2011) Steptococcus Agalactiae, Pathogen Safety Data Sheet. Public Health Agency of Canada. Available at: http://www.phac-aspc.gc.ca/lab-bio/res/psds-ftss/streptococcus-agalactiae-eng.php

  BACKGROUND

• Stensballe LG, Simonsen J, Jensen SM, Bonnelykke K, Bisgaard H. Use of antibiotics during pregnancy increases the risk of asthma in early childhood. J Pediatr. 2013 Apr;162(4):832-838.e3. doi: 10.1016/j.jpeds.2012.09.049. Epub 2012 Nov 6.

  PMID: 23140881 BACKGROUND

• Juarez Tomas MS, Ocana VS, Nader-Macias ME. Viability of vaginal probiotic lactobacilli during refrigerated and frozen storage. Anaerobe. 2004 Feb;10(1):1-5. doi: 10.1016/j.anaerobe.2004.01.002.

  PMID: 16701493 BACKGROUND

• Reid G. Probiotic and prebiotic applications for vaginal health. J AOAC Int. 2012 Jan-Feb;95(1):31-4. doi: 10.5740/jaoacint.sge_reid.

  PMID: 22468339 BACKGROUND

• Kaewsrichan J, Peeyananjarassri K, Kongprasertkit J. Selection and identification of anaerobic lactobacilli producing inhibitory compounds against vaginal pathogens. FEMS Immunol Med Microbiol. 2006 Oct;48(1):75-83. doi: 10.1111/j.1574-695X.2006.00124.x.

  PMID: 16965354 BACKGROUND

• Ortiz L, Ruiz F, Pascual L, Barberis L. Effect of two probiotic strains of Lactobacillus on in vitro adherence of Listeria monocytogenes, Streptococcus agalactiae, and Staphylococcus aureus to vaginal epithelial cells. Curr Microbiol. 2014 Jun;68(6):679-84. doi: 10.1007/s00284-014-0524-9. Epub 2014 Jan 28.

  PMID: 24469557 BACKGROUND

• Pascual LM, Daniele MB, Ruiz F, Giordano W, Pajaro C, Barberis L. Lactobacillus rhamnosus L60, a potential probiotic isolated from the human vagina. J Gen Appl Microbiol. 2008 Jun;54(3):141-8. doi: 10.2323/jgam.54.141.

  PMID: 18654035 BACKGROUND

• Patras KA, Wescombe PA, Rosler B, Hale JD, Tagg JR, Doran KS. Streptococcus salivarius K12 Limits Group B Streptococcus Vaginal Colonization. Infect Immun. 2015 Sep;83(9):3438-44. doi: 10.1128/IAI.00409-15. Epub 2015 Jun 15.

  PMID: 26077762 BACKGROUND

• Ho M, Chang YY, Chang WC, Lin HC, Wang MH, Lin WC, Chiu TH. Oral Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 to reduce Group B Streptococcus colonization in pregnant women: A randomized controlled trial. Taiwan J Obstet Gynecol. 2016 Aug;55(4):515-8. doi: 10.1016/j.tjog.2016.06.003.

  PMID: 27590374 BACKGROUND

• Wickens KL, Barthow CA, Murphy R, Abels PR, Maude RM, Stone PR, Mitchell EA, Stanley TV, Purdie GL, Kang JM, Hood FE, Rowden JL, Barnes PK, Fitzharris PF, Crane J. Early pregnancy probiotic supplementation with Lactobacillus rhamnosus HN001 may reduce the prevalence of gestational diabetes mellitus: a randomised controlled trial. Br J Nutr. 2017 Mar;117(6):804-813. doi: 10.1017/S0007114517000289. Epub 2017 Apr 3.

  PMID: 28367765 BACKGROUND

• Di Pierro F, Colombo M, Zanvit A, Risso P, Rottoli AS. Use of Streptococcus salivarius K12 in the prevention of streptococcal and viral pharyngotonsillitis in children. Drug Healthc Patient Saf. 2014 Feb 13;6:15-20. doi: 10.2147/DHPS.S59665. eCollection 2014.

  PMID: 24600248 BACKGROUND

• Acikgoz ZC, Gamberzade S, Gocer S, Ceylan P. [Inhibitor effect of vaginal lactobacilli on group B streptococci]. Mikrobiyol Bul. 2005 Jan;39(1):17-23. Turkish.

  PMID: 15900833 BACKGROUND

• Hayes K, Janssen P, Payne BA, Jevitt C, Johnston W, Johnson P, Butler M. Oral Probiotic Supplementation in Pregnancy to Reduce Group B Streptococcus Colonisation (OPSiP trial): study protocol for a double-blind parallel group randomised placebo trial. BMJ Open. 2024 Feb 5;14(2):e076455. doi: 10.1136/bmjopen-2023-076455.

  PMID: 38316588 DERIVED

Study Officials

• Michelle M Butler, PhD, RM

  Dublin City University

  PRINCIPAL INVESTIGATOR

• Patricia Janssen, PhD

  UBC School of Population and Public Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Randomisation will be centrally controlled using iSTAR, a web-based computerised randomisation platform at the BC Children's Hospital Research Institute, run by the PRE-EMPT (Pre-eclampsia Eclampsia Monitoring Prevention and Treatment) research group, UBC. PRE-EMPT will provide the randomisation platform, and web-linked drug supply management system. Randomisation will occur in random blocks of 2 and 4. Women will be randomised on a 1:1 ratio to probiotic:placebo.

Study Record Dates

• First Submitted: December 7, 2017
• First Posted: January 23, 2018
• Study Start: January 16, 2020
• Primary Completion: December 31, 2023
• Study Completion: December 31, 2024
• Last Updated: September 13, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: After primary trial results have been accepted for publication
• Access Criteria: Access criteria are de-identified data only and requires approval as stated above from the trial working group and local REB

Locations

CA (2)