CCA of SGB PCR Versus SGB Culture at 35-38 SA in the Optimization of Intrapartum Antibiotic Prophylaxis

Study Overview
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Brief Summary
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Early-onset neonatal infection (EONI), occur within 7 days of birth. They are most often due to Streptococcus B (GBS) and are associated with heavy and costly morbidity and mortality. The strategy combining antenatal detection (PV9) of GBS colonization and intrapartum antibiotic therapy has led to a spectacular decrease in the number of GBS EONI's that have become rare (0.3/1000 births). Current detection is based on the culture of a vaginal swab taken between 35 and 38 SA. Because the positive predictive value of PV9 compared to a culture on the day of delivery is 60%, two problems persist: i) 20% of women and newborns are sometimes unnecessarily exposed to antibiotics with known short-term and long-term harmful effects; ii) more than half of newborns developing EONI are born to mothers with negative PV9. There is a risk of not treating intrapartum colonization when PV9 is negative, and overtreating an uncolonized PV9-positive woman at the time of delivery. These inappropriate antibiotic therapies generate additional maternal-fetal care, examinations, treatments and hospitalizations with significant costs. Today, a feasible, rapid, sensitive (90-95%) and specific (95-98%) PCR test (Xpert GBS, CEPHEID) can be used to detect women colonized with GBS at the beginning of labor. A recent study (submitted for publication) including 782 women with risk factors for infection (intrapartum fever or prolonged rupture of membranes) who were subjected to PV9 and intrapartum PCR (IP PCR), identified 19% potential reclassification of GBS status, with a potential saving of 6% intrapartum antibiotic. We postulate that the replacement of PV9 by the generalized use of GBS intrapartum detection would optimize the indications for intrapartum antiobiotherapy, avoiding (i) unnecessary and deleterious care consumption in the absence of intrapartum GBS colonization, and (ii) avoidable EONIs occurring in the absence of intrapartum antiobiotherapy when GBS colonization has not been diagnosed. We propose to conduct a cost-consequence study because the criteria for clinically relevant judgments do not allow for cost-effectiveness or cost-utility analysis. Indeed, the intrapartum PCR strategy has consequences for both mother and child and these consequences cannot be aggregated. Thus, cost-consequence analysis based on criteria validated by clinicians and the literature seemed to us to be the most pragmatic approach and the most likely to help public decision making. The objective of this work is therefore to carry out a cost-consequence analysis comparing the intrapartum antibiotic prophylaxis strategy based on intrapartum GBS colonization screening by PCR, with the current strategy based on antenatal screening by culture between 35 and 38 SA.

Detailed Description
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• Inclusion visit : The patient is included in the GBS culture group or in the GBS PCR group determined by the randomization of the hospital in which she gives birth. A sample to perform the GBS PCR will be taken or not depending on the strategy in place in the center at the time of inclusion. The patient's management will be adapted according to the test result. The administration of intrapartum antibiotic therapy will be decided by the clinician in charge of the patient based on the result of antenatal GBS screening (PCR or culture) and taking into account the risk factors for EONI. In the GBS PCR group, the clinician will not have access to the result of the antenatal detection, even if the result is forgotten or technically impossible. • M1 follow-up visit (+/-5 days) by phone The study coordinator will follow up the patient by phone. The data collected are as below: Neonatal infection occurring within the first 6 days of life (this diagnosis requires hospital treatment by intravenous route, and will be verified on the hospitalization report), Endometritis in the first month after birth, Maternal and/or newborn antibiotic therapy (which one? how long? in which indication?) Hospitalization of the mother and/or newborn (which hospital, which department, how long? for what reason). Hospitalization report.

Official Title
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Cost-consequence Analysis of Intrapartum Streptococcal B Detection by PCR Versus Antenatal Culture at 35-38 SA in the Optimization of Intrapartum Antibiotic Prophylaxis

Conditions
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Streptococcus Agalactiae

Intervention / Treatment
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* Diagnostic Test: SGB PCR
* Diagnostic Test: SGB culture


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients admitted to the delivery room from 35SA upwards Planned vaginal delivery Patients who agreed to participate in the study and gave oral consent Patient affiliated to a social security system Exclusion Criteria: Complete dilatation (imminent delivery) Scheduled caesarean Term < 35 SA Death in utero Medical termination of pregnancy Does not speak French Opposition to participating in the study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Screening
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: intrapartum streptococcal B detection by PCR<br>The automatons will be installed by the laboratory in the delivery rooms and used delocalized by the obstetrical teams. Verification and validation of results will be ensured by the microbiology laboratory team, according to the recommendations and procedures already in use for off-site biology. | Diagnostic Test: SGB PCR<br>* This is a multi-center, randomized cluster and crossover study, and is open-label. The cluster is defined by the hospital center. Each center will therefore experiment with both strategies and the hospital centers will be randomized according to two arms: Arm n°1 : 1st period with SGB culture strategy and 2nd period with SGB PCR strategy. Arm n°2 : 1st period with SGB PCR Strategy and 2nd period with SGB culture Strategy Each inclusion period will last 6 weeks, with a 1-month wash-in period before each of the two inclusion periods of the study (training of the teams in intrapartum PCR detection). A wash-out period is not necessary in this study because the PCR machine will be removed from the centers when switching to the GBS culture strategy. During these two periods, all patients meeting the inclusion and non-inclusion criteria will be included in the study after presentation of the study and oral consent.<br>* Other names: Test Xpert® SGB and GeneXpert® Systems / GeneXpert® IV System (GX-4) - CEPHEID;|
| Active Comparator: intrapartum streptococcal B detection by SGB culture strategy<br> | Diagnostic Test: SGB culture<br>* This is a multi-center, randomized cluster and crossover study, and is open-label. The cluster is defined by the hospital center. Each center will therefore experiment with both strategies and the hospital centers will be randomized according to two arms: Arm n°1 : 1st period with SGB culture strategy and 2nd period with SGB PCR strategy. Arm n°2 : 1st period with SGB PCR Strategy and 2nd period with SGB culture Strategy Each inclusion period will last 6 weeks, with a 1-month wash-in period before each of the two inclusion periods of the study (training of the teams in intrapartum PCR detection). A wash-out period is not necessary in this study because the PCR machine will be removed from the centers when switching to the GBS culture strategy. During these two periods, all patients meeting the inclusion and non-inclusion criteria will be included in the study after presentation of the study and oral consent.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of total cost of antenatal culture versus intrapartum PCR screening strategy | Cost-consequence analysis: - Comparison of the total cost (collective perspective) of the screening strategy (expressed in euros) by antenatal culture versus intrapartum PCR from PV to 30 days postpartum. | Day 30 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neonatal morbidity-mortality criterion for NPI composite combining over the first 6 days of life | Neonatal morby-mortality criterion: composite criteria (expressed in %) | Day 6 | 
| Criteria for maternal-fetal exposure to antibiotics | Criteria for materno-foetal exposure to ATB (expressed in %) | Day 30 | 
| Maternal morbidity and mortality criteria at 30 days after delivery | a. Maternal mortality | Day 30 | 
| Proportion of appropriate intrapartum TBAs in the CRP arm compared to what would have been indicated using current recommendations | Intrapartum antibiotic therapy will be considered appropriate if i) PCR+ at time of delivery with intrapartum TBA ii) indeterminate PCRwith 2 risk factors for infection with intrapartum TBA, iii) PCR negative without intrapartum TBA iv) PCR negative or indeterminate with 0 or 1 risk factor for infection without intrapartum TBA. The comparison will focus on the proportion of TBAs administered in the SGB culture arm, which will be the state of practice and the reference in this pragmatic study. | Day 0 | 
| Feasibility criteria for the intrapartum GBS PCR screening strategy | Feasibility of off-site PCR in the birth room: % of PCRs performed for the entire eligible population Proportion of complete TBA ≥ 4h before delivery Frequency of PCR errors or invalids | Day 0 | 
| Net financial benefit (cost difference, annually and over 5 years) between different scenarios of dissemination of the strategy considered as efficient (Budget impact analysis; calculation on Excel) | Budget impact analysis allowing to evaluate the net financial benefit of the diffusion of the intrapartum antibiotic prophylaxis strategy based on the screening of GBS colonization in intrapartum by PCR, by comparing scenarios with different rates of development of this strategy, from the National Health Insurance perspective, annually and globally over a 5-year period. This analysis is performed in an Excel sheet, with the following parameters: mean cost of care for this strategy, initial market share of this strategy, expected speed of evolution of its market share compared to other existing strategies. | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Health economics, streptococcus B, screening, PCR