<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03251885</url>
  </required_header>
  <id_info>
    <org_study_id>0188-16-NHR</org_study_id>
    <nct_id>NCT03251885</nct_id>
  </id_info>
  <brief_title>Extended-spectrum β-lactamase -Producing Enterobacteriaceae (ESBL) Vertical Transmission in Women With Preterm Labor Versus Those in Term Pregnancy</brief_title>
  <official_title>Extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL) Vertical Carriage and Transmission Rates in Women With Preterm Labor Versus Women With Term Pregnancy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Western Galilee Hospital-Nahariya</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Western Galilee Hospital-Nahariya</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The aims of the study are to evaluate the rate of ESBL-producing Enterobacteriaceae&#xD;
      colonization among women in preterm labor and term labor, the incidence of maternal vertical&#xD;
      transmission of ESBL, and the clinical significance of ESBL in preterm infants.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Preterm delivery occurs before 37 weeks of gestation. Worldwide the preterm birth rate is&#xD;
      estimated to be about 11% and in Israel the preterm birth rate is approximately 7% (1, 2).&#xD;
      Preterm birth is the leading direct cause of neonatal death (death in the first 28 days of&#xD;
      life), and is responsible for 27% of neonatal deaths worldwide. Preterm births are divided to&#xD;
      spontaneous, due to preterm labor or preterm premature rupture of membrane, or iatrogenic&#xD;
      with labor induction due to maternal or fetal complications. The major risk factors for&#xD;
      spontaneous preterm birth include previous preterm delivery, multiple gestation, uterine&#xD;
      anomaly, systemic infection, history of cervical surgery and short cervical length. The&#xD;
      clinical findings of true labor (contractions plus cervical changes) are the same whether&#xD;
      labor occurs preterm or at term (3).&#xD;
&#xD;
      Treatment of women &lt;34 weeks of gestation with suspected preterm labor consist of a course of&#xD;
      betamethasone to reduce neonatal morbidity and mortality associated with preterm birth,&#xD;
      tocolytic drugs for up to 48 hours to delay delivery, antibiotics for Group B Streptococcus&#xD;
      (GBS) chemoprophylaxis and magnesium sulfate for pregnancies at 24 to 32 weeks of gestation&#xD;
      to provide neuroprotection against cerebral palsy and other types of severe motor dysfunction&#xD;
      (4). A 2014 Cochrane review of randomized trials of intrapartum antibiotic treatment of women&#xD;
      colonized with GBS found that intrapartum antibiotic prophylaxis resulted in a significant&#xD;
      reduction in early-onset neonatal GBS infection and a non-significant reduction in neonatal&#xD;
      mortality (5). Intrapartum antibiotic prophylaxis is given in cases of positive screening&#xD;
      culture for GBS from either vagina or rectum, positive history of birth of an infant with&#xD;
      early-onset GBS disease or GBS bacteriuria during the current pregnancy (6, 7, 8). Other risk&#xD;
      factors of developing early-onset sepsis include Intrapartum fever ≥38ºC, preterm labor (&lt;37&#xD;
      weeks of gestation) and prolonged rupture of membranes (≥18 hours); women who have these risk&#xD;
      factors should receive antibiotic prophylaxis in labor (9).&#xD;
&#xD;
      The Israeli Center for Disease Control report concerning early-onset neonatal invasive GBS&#xD;
      disease showed a relatively similar incidence of invasive disease over the years 2006-2015&#xD;
      (10). In contrast, a recent report showed a marked increase in Gram-negative early-onset&#xD;
      sepsis. The incidence of early-onset Gram-negative sepsis in Israel during the years&#xD;
      2008-2014 was 0.49 for 1000 live births and increased from 0.16 per 1000 in 2008 to 0.32 in&#xD;
      2014 (11). The incidence of E.coli early-neonatal sepsis rises significantly in preterm&#xD;
      births (55 in preterm births vs. 26 in term) and in 2014 the burden of disease caused by&#xD;
      E.coli was higher than GBS.&#xD;
&#xD;
      Most Gram-negative pathogens are resistant to ampicillin. Resistance of isolated E.coli to&#xD;
      second and third generation cephalosporins was noted in 8.3% of early-onset infections,&#xD;
      particularly in preterm and low-birth weight neonates and imply transmission of resistant&#xD;
      strains during labor. Extended-spectrum β- lactamase-producing Enterobacteriaceae (ESBL) are&#xD;
      pathogens which are practically resistant to all penicillins and cephalosporines. ESBL-&#xD;
      producing Enterobacteriaceae may also harbor additional antibiotic-resistant genes against&#xD;
      aminoglycosides, trimethoprim-sulfamethoxazole, ciprofloxacin and other agents (12). Although&#xD;
      the prevalence of ESBL carriage is unknown, it is clearly increasing in the community and in&#xD;
      many parts of the world 10-40% of strains of E.coli and Klebsiella pneumoniae express ESBL.&#xD;
      However, there are no guidelines concerning surveillance cultures of pregnant women both in&#xD;
      term or preterm labor for ESBL colonization although neonatal screening in neonatal intensive&#xD;
      care units (NICU), on admission and periodically after, is accepted in order to prevent ESBL&#xD;
      transmission in the NICU. In addition, we would like to compare the rate of ESBL carriage&#xD;
      rate in women in preterm versus term labor.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">April 12, 2017</start_date>
  <completion_date type="Anticipated">June 2022</completion_date>
  <primary_completion_date type="Anticipated">December 2021</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Maternal rectal and vaginal specimens will be compared to assess influence of culturing site and admission and labor specimens will be compared for possible influence of hospitalization on ESBL carriage</measure>
    <time_frame>two years</time_frame>
    <description>positive ESBL vs. negative ESBL</description>
  </primary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Anticipated">300</enrollment>
  <condition>Preterm Labor</condition>
  <arm_group>
    <arm_group_label>women with preterm labor</arm_group_label>
    <description>pregnant women &lt; 37 weeks of gestations with regular uterine contractions and &gt; 3 cm dilation, &gt; 80% effacement</description>
  </arm_group>
  <arm_group>
    <arm_group_label>women with term pregnancy</arm_group_label>
    <description>pregnant women &gt; 37 weeks of gestation</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>swabs</intervention_name>
    <description>Two swabs will be taken at each screen: one from the vagina and the other from the rectum for vaginal and rectal assessment of maternal colonization</description>
    <arm_group_label>women with preterm labor</arm_group_label>
    <arm_group_label>women with term pregnancy</arm_group_label>
  </intervention>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Two swabs will be taken at each screen: one from the vagina and the other from the rectum for&#xD;
      vaginal and rectal assessment of maternal colonization. Maternal colonizing ESBL strain will&#xD;
      be compared with infant's strain, if detected by the routine weekly NICU rectal surveillance&#xD;
      for ESBL carriage.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        women in preterm labor women in term labor&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Preterm delivery &lt;37 weeks of gestation&#xD;
&#xD;
          -  term delivery &gt; 37 weeks of gestation&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Unknown gestational age&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <gender_based>Yes</gender_based>
    <gender_description>female only</gender_description>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>45 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Maya Wolf, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Galilee Medical Center</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Maya Wolf, MD</last_name>
    <phone>972--507887800</phone>
    <email>mayaw@gmc.gov.il</email>
  </overall_contact>
  <location>
    <facility>
      <name>Galil Medical Center</name>
      <address>
        <city>Nahariyya</city>
        <country>Israel</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Maya Wolf, MD</last_name>
      <phone>972-507887800</phone>
      <email>homesickid@yahoo.com</email>
    </contact>
  </location>
  <location_countries>
    <country>Israel</country>
  </location_countries>
  <verification_date>March 2021</verification_date>
  <study_first_submitted>August 14, 2017</study_first_submitted>
  <study_first_submitted_qc>August 14, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 16, 2017</study_first_posted>
  <last_update_submitted>March 3, 2021</last_update_submitted>
  <last_update_submitted_qc>March 3, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">March 8, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Western Galilee Hospital-Nahariya</investigator_affiliation>
    <investigator_full_name>Dr. Maya Wolf</investigator_full_name>
    <investigator_title>MD</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Premature Birth</mesh_term>
    <mesh_term>Obstetric Labor, Premature</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03251885
org study id: 0188-16-NHR
nct id: NCT03251885
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The aims of the study are to evaluate the rate of ESBL-producing Enterobacteriaceae
      colonization among women in preterm labor and term labor, the incidence of maternal vertical
      transmission of ESBL, and the clinical significance of ESBL in preterm infants.
Preterm delivery occurs before 37 weeks of gestation. Worldwide the preterm birth rate is
      estimated to be about 11% and in Israel the preterm birth rate is approximately 7% (1, 2).
      Preterm birth is the leading direct cause of neonatal death (death in the first 28 days of
      life), and is responsible for 27% of neonatal deaths worldwide. Preterm births are divided to
      spontaneous, due to preterm labor or preterm premature rupture of membrane, or iatrogenic
      with labor induction due to maternal or fetal complications. The major risk factors for
      spontaneous preterm birth include previous preterm delivery, multiple gestation, uterine
      anomaly, systemic infection, history of cervical surgery and short cervical length. The
      clinical findings of true labor (contractions plus cervical changes) are the same whether
      labor occurs preterm or at term (3).

      Treatment of women <34 weeks of gestation with suspected preterm labor consist of a course of
      betamethasone to reduce neonatal morbidity and mortality associated with preterm birth,
      tocolytic drugs for up to 48 hours to delay delivery, antibiotics for Group B Streptococcus
      (GBS) chemoprophylaxis and magnesium sulfate for pregnancies at 24 to 32 weeks of gestation
      to provide neuroprotection against cerebral palsy and other types of severe motor dysfunction
      (4). A 2014 Cochrane review of randomized trials of intrapartum antibiotic treatment of women
      colonized with GBS found that intrapartum antibiotic prophylaxis resulted in a significant
      reduction in early-onset neonatal GBS infection and a non-significant reduction in neonatal
      mortality (5). Intrapartum antibiotic prophylaxis is given in cases of positive screening
      culture for GBS from either vagina or rectum, positive history of birth of an infant with
      early-onset GBS disease or GBS bacteriuria during the current pregnancy (6, 7, 8). Other risk
      factors of developing early-onset sepsis include Intrapartum fever ≥38ºC, preterm labor (<37
      weeks of gestation) and prolonged rupture of membranes (≥18 hours); women who have these risk
      factors should receive antibiotic prophylaxis in labor (9).

      The Israeli Center for Disease Control report concerning early-onset neonatal invasive GBS
      disease showed a relatively similar incidence of invasive disease over the years 2006-2015
      (10). In contrast, a recent report showed a marked increase in Gram-negative early-onset
      sepsis. The incidence of early-onset Gram-negative sepsis in Israel during the years
      2008-2014 was 0.49 for 1000 live births and increased from 0.16 per 1000 in 2008 to 0.32 in
      2014 (11). The incidence of E.coli early-neonatal sepsis rises significantly in preterm
      births (55 in preterm births vs. 26 in term) and in 2014 the burden of disease caused by
      E.coli was higher than GBS.

      Most Gram-negative pathogens are resistant to ampicillin. Resistance of isolated E.coli to
      second and third generation cephalosporins was noted in 8.3% of early-onset infections,
      particularly in preterm and low-birth weight neonates and imply transmission of resistant
      strains during labor. Extended-spectrum β- lactamase-producing Enterobacteriaceae (ESBL) are
      pathogens which are practically resistant to all penicillins and cephalosporines. ESBL-
      producing Enterobacteriaceae may also harbor additional antibiotic-resistant genes against
      aminoglycosides, trimethoprim-sulfamethoxazole, ciprofloxacin and other agents (12). Although
      the prevalence of ESBL carriage is unknown, it is clearly increasing in the community and in
      many parts of the world 10-40% of strains of E.coli and Klebsiella pneumoniae express ESBL.
      However, there are no guidelines concerning surveillance cultures of pregnant women both in
      term or preterm labor for ESBL colonization although neonatal screening in neonatal intensive
      care units (NICU), on admission and periodically after, is accepted in order to prevent ESBL
      transmission in the NICU. In addition, we would like to compare the rate of ESBL carriage
      rate in women in preterm versus term labor.
observational model: Cohort
time perspective: Prospective
measure: Maternal rectal and vaginal specimens will be compared to assess influence of culturing site and admission and labor specimens will be compared for possible influence of hospitalization on ESBL carriage
time frame: two years
description: positive ESBL vs. negative ESBL
arm group label: women with preterm labor
description: pregnant women < 37 weeks of gestations with regular uterine contractions and > 3 cm dilation, > 80% effacement
arm group label: women with term pregnancy
description: pregnant women > 37 weeks of gestation
intervention type: Other
intervention name: swabs
description: Two swabs will be taken at each screen: one from the vagina and the other from the rectum for vaginal and rectal assessment of maternal colonization
arm group label: women with preterm labor
arm group label: women with term pregnancy
Two swabs will be taken at each screen: one from the vagina and the other from the rectum for
      vaginal and rectal assessment of maternal colonization. Maternal colonizing ESBL strain will
      be compared with infant's strain, if detected by the routine weekly NICU rectal surveillance
      for ESBL carriage.
study pop: 
sampling method: Probability Sample
criteria: 
gender: Female
gender based: Yes
gender description: female only
minimum age: 18 Years
maximum age: 45 Years
healthy volunteers: No
last name: Maya Wolf, MD
role: Principal Investigator
affiliation: Galilee Medical Center
last name: Maya Wolf, MD
phone: 972--507887800
email: mayaw@gmc.gov.il
facility: 
status: Recruiting
contact: 
country: Israel
responsible party type: Principal Investigator
investigator affiliation: Western Galilee Hospital-Nahariya
investigator full name: Dr. Maya Wolf
investigator title: MD
mesh term: Premature Birth
mesh term: Obstetric Labor, Premature