Clinical trial NCT02511444: Intrapartum Rapid GBS Testing in Patients Presenting With Threatened Preterm Labor
Official title: Intrapartum Rapid GBS Testing in Patients Presenting With Threatened Preterm Labor
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Group B Streptococcus
Keywords: GBS
GBS culture
GBS PCR
GBS colonization
Lead sponsor: MemorialCare Health System
Sponsor class: OTHER
First posted: 2015-07-30
Enrollment: 342
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: The purpose of this study is to evaluate the test characteristics of a rapid intrapartum real- time polymerase chain reaction (RT-PCR) compared to the intrapartum GBS culture as the standard in preterm patients presenting with threatened preterm labor or with obstetric indications for preterm delivery.

Detailed description: Group B streptococcus (GBS) or Streptococcus agalactiae is a gram-positive bacterium that colonizes 10-40% of maternal gastrointestinal and urogenital tract sites. Maternal colonization remains the primary risk factor and the leading cause of early onset GBS disease in infants in the United States. Transmission of GBS to the neonate in early onset GBS cases occurs at the time of labor and delivery, with a transmission rate of 52.5% if no intrapartum antibiotics are used. Of those neonates, 1-2% term infants and 8% of preterm infants will develop early onset disease.

The Centers for Disease Control (CDC) recommends universal screening at 35-37 weeks via culture of the vagina and rectum. If this is performed ≤5 weeks before delivery, it has a sensitivity of 85% and a negative predictive value of 95-98%. There is a downside to screening remote from delivery however; vaginal GBS colonization fluctuates in the same woman over time, thus rendering possibly inaccurate GBS results. It has been reported that at least 10% of antenatal GBS negative women turned positive at the time of labor. This may suggest that screening at the time of delivery is a more accurate method of predicting actual GBS colonization status. In fact, a majority of neonatal GBS sepsis occurs in infants born to mothers with a negative antepartum screening culture.

Currently, a standard GBS culture may take up to 3 days to obtain results. A rapid diagnostic test has more recently been studied as a possible method of GBS screening - real-time polymerase chain reaction (RT-PCR). Prior studies of RT-PCR, specifically the Cepheid GeneXpert GBS assay used at Miller's Children's and Women's Hospital, have reported sensitivity from 85-98.5% and specificity of 96-99.6% using data from term gestations. The CDC currently permits the use of RT-PCR as a rapid screening test for those with unknown status at term.

Several reports demonstrate that RT-PCR is a rapid, more sensitive method than standard culture for determining the intrapartum GBS colonization status. Some studies have also demonstrated the ability of RT-PCR to identify patients who would otherwise be missed by traditional GBS culture. A study by Mueller et al demonstrated that out of 64 patients with positive RT-PCR results, 10 were actually negative on culture. A cost-effectiveness analysis has demonstrated that PCR intrapartum screening strategy is not any less cost-effective than traditional culture and confers a significant decrease in early onset GBS disease in term gestations.

Preterm infants suffer the highest rate of mortality from GBS infection, with up to 30% mortality in those \< 33 weeks affected by GBS sepsis. Identifying GBS colonization is thus imperative in the 7-11% of all pregnancies affected by preterm labor, given that they will not have undergone universal screening yet (which typically occurs at 35-37 weeks). While the CDC recommends giving antibiotics to patients with unknown GBS status at substantial risk for preterm delivery, implementation of this recommendation is poor.

Advantages of the RT-PCR are that its results will come back much more rapidly than the standard culture and may assist in management of these critical patients, 75 min vs 3 days, respectively. Accurate screening for GBS in a rapid fashion, especially in preterm infants, where the risk of GBS infection is most serious, can potentially allow antibiotics to be used appropriately.

The investigators seek to evaluate the utility of RT-PCR for screening of GBS in women at risk of preterm labor with an unknown GBS status. The investigators also aim to identify the ability of RT-PCR to identify GBS colonization in patients who would have otherwise been missed by culture.

Eligibility criteria: Inclusion Criteria:

* Age ≥ 18 years
* Pregnant women presenting for unplanned obstetrical care at a participating clinical study site
* Gestational age between 21 6/7 and 36 6/7 weeks
* Subject has not participated in the study before
* Subject agrees to complete all aspects of the study and provide informed consent in accordance with applicable regulations
* Signs and/or symptoms suggestive of preterm labor, whereby the managing clinician suspects preterm labor
* Uterine contractions (with or without pain)
* Intermittent lower abdominal pain, dull backache, pelvic pressure
* Vaginal bleeding during the second and third trimester
* Menstrual-like intestinal cramping (with or without diarrhea)
* Change in vaginal discharge (amount, color, or consistency)
* Vague sense of discomfort characterized as "not feeling right"
* Change in cervical exam (cervical dilation, effacement, or consistency)
* Signs and symptoms necessitating preterm delivery (i.e abruption, preeclampsia, hemolysis elevated liver enzymes, low platelet (HELLP) syndrome, ruptured membranes, chorioamnionitis, fetal indications)

Exclusion Criteria:

* Exposure to antibiotics within 1 week prior to enrollment (15)
* Known GBS bacteriuria at the time of enrollment
* Prior history of neonatal GBS sepsis

Primary outcomes:
measure: Sensitivity of intrapartum GBS real time PCR compared to intrapartum GBS culture
timeFrame: up to one and a half year
measure: Positive predictive value of GBS Real time PCR performed intrapartum
timeFrame: up to one and a half year
measure: Negative predictive value of GBS real time PCR performed intrapartum
timeFrame: up to one and a half year
measure: Specificity of intrapartum GBS real time PCR compared to intrapartum GBS
timeFrame: up to one and a half year
Secondary outcomes:
measure: Neonatal GBS septicemia
timeFrame: up to one and a half year
measure: Composite neonatal morbidity
timeFrame: up to one and a half year
measure: number of neonatal intensive care unit days
timeFrame: up to one and a half year
measure: Neonatal mortality rate
timeFrame: up to one and a half year
measure: necrotizing enterocolitis
timeFrame: up to one and a half year
measure: Gestational age at delivery
timeFrame: up to one and a half year
measure: vaginal delivery
timeFrame: up to one and a half year
measure: Postpartum hemorrhage
timeFrame: up to one and a half year
measure: Maternal intrapartum chorioamnionitis
timeFrame: up to one and a half year
measure: Maternal postpartum endometritis
timeFrame: up to one and a half year
measure: Neonatal respiratory distress
timeFrame: up to one and half year
Other outcomes:
measure: Neonatal intraventricular hemorrhage
timeFrame: up to one and half year
measure: Neonatal pneumonia
timeFrame: up to one and half year
measure: Neonatal osteomyelitis
timeFrame: up to one and half year
measure: Neonatal bacteremia
timeFrame: up to one and half year
measure: Neonatal meningitis
timeFrame: up to one and half year
measure: cesarean delivery
timeFrame: up to one and half year
measure: composite maternal morbidity
timeFrame: up to one and half year
Locations:
city: Long Beach
country: United States
facility: Miller Children's & Women's Hospital Long Beach
state: California
Study officials:
affiliation: Maternal Fetal Medicine
name: Alex Fong, MD
role: PRINCIPAL_INVESTIGATOR
References:
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