Clinical trial NCT01479478: Effects of Oral Probiotic Supplementation on Group B Strep (GBS) Rectovaginal Colonization in Pregnancy
Official title: Oral Probiotic Supplementation and Group B Streptococcus Rectovaginal Colonization in Pregnant Women: a Randomized Double-blind Placebo-controlled Trial.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Infection
Pregnancy
Lead sponsor: Stanford University
Sponsor class: OTHER
First posted: 2011-11-24
Enrollment: 251
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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.

Eligibility 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)

Primary outcomes:
measure: Count of Participants With Positive Group B Streptococcus Rectovaginal Colonization Status at 35- 37 Weeks' Gestational Age
timeFrame: 35 to 37 weeks gestational age
Secondary outcomes:
measure: Count of Participants With Urinary Tract Infection
timeFrame: From enrollment up to delivery hospitalization (up to 42 weeks gestation)
measure: Count of Participants With Intrapartum Chorioamnionitis
timeFrame: From time of labor onset until delivery (up to 42 weeks of gestation)
measure: Count of Participants With Endometritis
timeFrame: From time of delivery up to 6 weeks postpartum
measure: Count of Participants With Cellulitis
timeFrame: From time of delivery up to 6 weeks postpartum
measure: Count of Participants With Bacteremia
timeFrame: From time of labor onset up to 6 weeks postpartum
measure: Count of Participants With Sepsis
timeFrame: From labor onset up to 6 weeks postpartum
measure: Count of Participants With Other Infectious Morbidity
timeFrame: From time of labor onset up to 6 weeks postpartum
measure: Gestational Age at Delivery
timeFrame: At time of delivery (up to 42 weeks of gestation)
measure: Apgar Score at 1 and 5 Minutes Following Delivery
timeFrame: At time of delivery (up to 42 weeks of gestation)
measure: Neonatal Bilirubin Level
timeFrame: Up to 14 days following delivery
measure: Neonatal C-reactive Protein Level
timeFrame: Up to 14 days following delivery
measure: Count of Neonates Requiring a "Rule-out Sepsis Evaluation"
timeFrame: Up to 14 days following delivery
measure: Count of Neonates With Sepsis
timeFrame: Up to 14 days following delivery
measure: Count of Neonates With Pneumonia
timeFrame: Up to 14 days following delivery
measure: Count of Neonates With Meningitis
timeFrame: Up to 14 days following delivery
measure: Count of Neonates With Intensive-care Unit Admission
timeFrame: Up to 14 days following delivery
measure: Length of Neonatal Hospital Stay
timeFrame: Up to 14 days following delivery
Other outcomes:
Locations:
city: Aptos
country: United States
facility: Aptos Women's Health Center
state: California
city: Santa Cruz
country: United States
facility: Dominican Hospital
state: California
city: Stanford
country: United States
facility: Stanford University School of Medicine/Lucile Packard Children's Hospital
state: California
Study officials:
affiliation: Stanford University School of Medicine/Lucile Packard Children's Hospital
name: Natali Aziz, MD
role: PRINCIPAL_INVESTIGATOR
References: