Effects of Oral Probiotic Supplementation on Group B Strep (GBS) Rectovaginal Colonization in Pregnancy

• ClinicalTrials.gov Identifier: NCT01479478
• Recruitment Status: Completed
• First Posted: November 24, 2011
• Results First Posted: August 20, 2018
• Last Update Posted: August 20, 2018
• Sponsor: Stanford University
• Information provided by (Responsible Party): Natali Aziz, Stanford University

Study Description

Brief Summary:

The investigators wish to determine if oral probiotic supplementation during the second half of pregnancy decreases maternal GBS recto-vaginal colonization at 35-37 weeks' gestational age, thereby decreasing need for maternal antibiotic administration at time of labor. The importance of this study is that it may offer a safer alternative to antibiotic treatment of group B Streptococcus (GBS) colonized pregnant women.

Condition or disease	Intervention/treatment	Phase
Infection; Pregnancy	Drug: Placebo; Dietary Supplement: Probiotic dietary supplement	Not Applicable

Detailed Description:

1. Screening: All pregnant women prior to 28 weeks gestational age. Patients who choose to enroll and who will not deliver at Lucile Packard Childrens Hospital at Stanford will sign release of medical information forms for study personnel to access pregnancy outcomes. Patients receiving obstetric care at any of the satellite research sites in Santa Cruz will also be offered enrollment in the study.
2. Women will continue regular and routine obstetric care and clinic visits.
3. Placebo vs probiotic daily regimen: We plan to begin administration of product and placebo at 20 weeks gestation, and no later than 28 weeks gestation until delivery. Once a women is enrolled in the study, she will be randomized to either the placebo or the probiotic group.
4. At the time of randomization, the patient will receive her month supply of 30 capsules; The allocation arm will be double-blinded.
5. The investigators will schedule the women for routine monthly obstetric visits (more often if clinically required) during which time they will also meet with one of the investigators. The investigator at each monthly visit will provide an additional monthly allotment of 30 capsules. The capsule bottle from the previous cycle will be collected and dated if there are capsules remaining in the bottle. Remaining capsules will be counted and refrigerated for future use.
6. The investigators will collect history data including safety data per the questionnaire and will document compliance with the study.
7. GBS recto-vaginal screening: The investigators will enroll the women in the study and we will perform the standard GBS colonization screening (using standard GBS recto-vaginal cultures) at 36 weeks.
8. Additionally, subjects may opt to have serial vaginal swabs collected to assess potential beneficial effects of probiotics on the vaginal microbiota and bacterial vaginosis (BV) status. Vaginal swabs will be collected (either by study personnel or self-collected by the study participant). Swabs will be inserted 1-2 inches into the vaginal introitus and spun for 20 seconds and then withdrawn. Swabs will be collected at the following time points: prior to probiotic/placebo initiation, every 1-4 weeks from time of enrollment to time of delivery, and postpartum serially up to 12 months. These swabs will be stored at -20 degrees Celsius or colder for additional microbiologic analyses.
9. Additionally, placental tissue may be collected at time of delivery for possible future microbiome and/or other analyses.
10. Women who suffer a premature rupture of the membranes, deliver before 36 weeks gestation, or go into labor before the GBS culture result is available, will receive the standard GBS antibiotic prophylaxis.
11. Labor: The patient will receive standard delivery and newborn care. Patients with a positive GBS culture will be treated with standard antibiotics in labor.
12. Postpartum and neonatal care: The patient will receive routine postpartum care per the obstetric team. Data regarding her postpartum course and neonatal outcomes will be collected.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 251 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Oral Probiotic Supplementation and Group B Streptococcus Rectovaginal Colonization in Pregnant Women: a Randomized Double-blind Placebo-controlled Trial.
• Study Start Date: November 2011
• Actual Primary Completion Date: July 26, 2017
• Actual Study Completion Date: July 26, 2017

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Probiotic dietary supplement; Probiotic dietary supplement one capsule once per day until delivery.	Dietary Supplement: Probiotic dietary supplement; Dietary Supplement: Lactobacillus rhamnosus GR-1, Lactobacillus reuteri RC -14; Other Names: Other Names:; Jarrow's fem-dophilus
Placebo Comparator: Placebo; Placebo capsule, one daily until delivery.	Drug: Placebo; One placebo capsule daily.; Other Name: Sugar pill

Outcome Measures

Primary Outcome Measures :

1. Count of Participants With Positive Group B Streptococcus Rectovaginal Colonization Status at 35- 37 Weeks' Gestational Age [ Time Frame: 35 to 37 weeks gestational age ]
   Gestational age is given in a format of full weeks.

Secondary Outcome Measures :

1. Count of Participants With Urinary Tract Infection [ Time Frame: From enrollment up to delivery hospitalization (up to 42 weeks gestation) ]
2. Count of Participants With Intrapartum Chorioamnionitis [ Time Frame: From time of labor onset until delivery (up to 42 weeks of gestation) ]
   Intrapartum chorioamnionitis is maternal temperature above 38.0 degrees Celsius and one or more of the following findings: fetal tachycardia; maternal tachycardia; uterine tenderness; purulent or malodorous amniotic fluid, or elevated maternal white blood cell count.
3. Count of Participants With Endometritis [ Time Frame: From time of delivery up to 6 weeks postpartum ]
   Endometritis is a uterine (myometrial) infection.
4. Count of Participants With Cellulitis [ Time Frame: From time of delivery up to 6 weeks postpartum ]
   Cellulitis is a bacterial skin infection.
5. Count of Participants With Bacteremia [ Time Frame: From time of labor onset up to 6 weeks postpartum ]
   Bacteremia is defined as presence of bacteria in the blood.
6. Count of Participants With Sepsis [ Time Frame: From labor onset up to 6 weeks postpartum ]
   Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated response of the body to an infection.
7. Count of Participants With Other Infectious Morbidity [ Time Frame: From time of labor onset up to 6 weeks postpartum ]
   Other infectious morbidity included maternal mastitis or pneumonia.
8. Gestational Age at Delivery [ Time Frame: At time of delivery (up to 42 weeks of gestation) ]
   Gestational age at delivery is presented as weeks.
9. Apgar Score at 1 and 5 Minutes Following Delivery [ Time Frame: At time of delivery (up to 42 weeks of gestation) ]
   Apgar score is a measure to quickly assess the neonatal health status from time of delivery. Score ranges from 0-10. Lower scores correspond to worse health state; neonates with scores below 5 are considered to have poor prognosis.
10. Neonatal Bilirubin Level [ Time Frame: Up to 14 days following delivery ]
11. Neonatal C-reactive Protein Level [ Time Frame: Up to 14 days following delivery ]
    Maximum neonatal C-reactive protein level
12. Count of Neonates Requiring a "Rule-out Sepsis Evaluation" [ Time Frame: Up to 14 days following delivery ]
    Outcome was based on performance of neonatal blood culture.
13. Count of Neonates With Sepsis [ Time Frame: Up to 14 days following delivery ]
14. Count of Neonates With Pneumonia [ Time Frame: Up to 14 days following delivery ]
15. Count of Neonates With Meningitis [ Time Frame: Up to 14 days following delivery ]
16. Count of Neonates With Intensive-care Unit Admission [ Time Frame: Up to 14 days following delivery ]
17. Length of Neonatal Hospital Stay [ Time Frame: Up to 14 days following delivery ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 55 Years (Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

1. Pregnant women between 20-28 weeks gestation.
2. 18 years of age or older.
3. Singleton gestation.

Exclusion Criteria:

1. Preexisting morbidity: Immunocompromised status (HIV +; malignancy; history of organ transplant; chronic steroid therapy; autoimmune disease requiring treatment during pregnancy, and other immunocompromised states); Type 1 diabetes and type 2 diabetes;congenital cardiac disease and cardiac valvular disease requiring antibiotic prophylaxis during procedure/labor; pulmonary disease (except mild asthma); renal disease; chronic hepatic disease (Hepatitis B, C); inflammatory bowel disease (Crohn's disease or ulcerative colitis); stomach or duodenal ulcer; bowel resection, gastric bypass, and chronic indwelling venous, bladder, or gastric catheter.
2. Multi-fetal gestation.
3. Use of probiotics preparations in the 3 months prior to beginning of the study treatment or use of any additional probiotics preparations (other than study treatment) at any time during the study period (including over the counter food supplements such as Activia, BioK, other oral or vaginal probiotics products (BUT not including other common forms of yogurt).
4. Chronic (daily) use of broad spectrum antibiotics.
5. History of infant with GBS sepsis.
6. Intrauterine Growth Restriction (IUGR), Fetal Anomalies-major diagnosed at time of second trimester anatomy ultrasound
7. Anticipated delivery <35 wks for maternal/fetal indication
8. Placenta previa or accreta (with anticipated delivery prior to 35 weeks)

Contacts and Locations

Locations

United States, California

Aptos Women's Health Center

Aptos, California, United States, 95003

Dominican Hospital

Santa Cruz, California, United States, 95065

Stanford University School of Medicine/Lucile Packard Children's Hospital

Stanford, California, United States, 94305

Sponsors and Collaborators

Stanford University

Investigators

• Principal Investigator: Natali Aziz, MD; Stanford University School of Medicine/Lucile Packard Children's Hospital

  Study Documents (Full-Text)

Documents provided by Natali Aziz, Stanford University:

Study Protocol  [PDF] November 19, 2013

Statistical Analysis Plan  [PDF] July 14, 2017

More Information

• Responsible Party: Natali Aziz, Clinical Assistant Professor, Stanford University
• ClinicalTrials.gov Identifier: NCT01479478
• Other Study ID Numbers: 18840
• First Posted: November 24, 2011
• Results First Posted: August 20, 2018
• Last Update Posted: August 20, 2018
• Last Verified: August 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No