<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/NCT02225717</url>
  </required_header>
  <id_info>
    <org_study_id>P140502</org_study_id>
    <nct_id>NCT02225717</nct_id>
  </id_info>
  <brief_title>Identification of Spontaneous Delivery Markers</brief_title>
  <acronym>TrophY2</acronym>
  <official_title>Markers of Fetal Membranes Remodelling in Cervicovaginal Fluid and Delivery</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Assistance Publique - Hôpitaux de Paris</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Assistance Publique - Hôpitaux de Paris</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The investigators project aims to identify, in pregnant women, discriminating molecules to&#xD;
      allow an early detection of women who will spontaneously deliver prematurely, suitable in&#xD;
      routine clinical practice.&#xD;
&#xD;
      Human parturition is tightly correlated with hormonal changes at the maternal-fetal interface&#xD;
      during pregnancy, that may control cell interactions and fetal membranes (the water bag)&#xD;
      remodelling. Precocious remodelling may lead to a premature onset of labor, associated or not&#xD;
      with premature rupture of membrane whether the cause is infectious or not.&#xD;
&#xD;
      In this regard, remodelled fetal membranes overlying the cervix may discharge signals that&#xD;
      could be detectable in cervico-vaginal fluids and serve as biomarkers of the imminence of&#xD;
      delivery. Such information on delivery timing may be of great importance for an adequate&#xD;
      prediction that would change drastically the management of threatening preterm delivery.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Prematurity is a major Public Health concern in developed countries, since it is the first&#xD;
      cause of perinatal morbi-mortality and of cerebral palsy in early childhood. Premature birth&#xD;
      rate has risen by 36 percent over the last 25 years to reach 7.2% in 2010 in France.&#xD;
      Antenatal corticosteroids administration before 34 weeks and in utero transfer in&#xD;
      high-qualified maternity wards are ones of the rare antenatal therapies recommended to&#xD;
      improve neonatal complications of preterm delivery. Early identification of women with high&#xD;
      risk of preterm birth should be helpful to implement those prophylactic measures. Moreover&#xD;
      discriminating true preterm labor (PTL) vs. symptoms of PTL in women, who will finally&#xD;
      deliver at term, would reduce unnecessary hospitalizations and prescriptions.&#xD;
&#xD;
      During human gestation, fetal membranes (the &quot;water bag&quot;) encompass the amnion, facing the&#xD;
      amniotic cavity, and the chorion, lining the maternal decidua and comprising trophoblast&#xD;
      cells. Membranes usually remain intact until their spontaneous rupture, close to the first&#xD;
      stage of labor at term. Often seen as a simple inert shell, with a role of &quot;airbag&quot; for the&#xD;
      developing fetus, the membranes provide yet a large surface of interaction between maternal&#xD;
      and fetal tissues and function as a transient endocrine organ with immune properties.&#xD;
&#xD;
      Specific remodelling of the membranes is observed at term prior to delivery. During this&#xD;
      remodelling, drastic changes in extracellular matrix occur, with the secretion of specific&#xD;
      molecules. The investigators hypothesize that premature fetal membranes remodelling occurs&#xD;
      weeks prior to actual birth and may be able to be detected in women at risk for preterm&#xD;
      birth, i.e. presenting signs of PTL. This study investigates if the detection of fetal&#xD;
      membranes remodelling in cervico-vaginal fluids can accurately identify those women at&#xD;
      greatest risk for preterm birth. A prospective cohort of pregnant women will before 32 weeks&#xD;
      of gestation with symptoms of preterm labor be enrolled. As negative controls, healthy&#xD;
      pregnant women at 12-15 or 35-36 weeks of gestation or non-pregnant women will be recruited.&#xD;
      As positive controls, healthy pregnant woman at term (over 38 weeks of gestation) will be&#xD;
      enrolled. The main outcome assessed is preterm delivery.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 14, 2014</start_date>
  <completion_date type="Actual">April 16, 2018</completion_date>
  <primary_completion_date type="Actual">November 14, 2017</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Screening</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Delivery</measure>
    <time_frame>until Day 14</time_frame>
    <description>Assessed among patients in preterm labor between 24 - 32 GA</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Delivery before 34 GA</measure>
    <time_frame>until Day 14</time_frame>
    <description>Assessed among patients in preterm labor between 24 - 32 GA</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>composite Prenatal maternal care</measure>
    <time_frame>until Delivery</time_frame>
    <description>Assessed by :&#xD;
number of hospitalization,&#xD;
total duration of hospitalization for preterm labor,&#xD;
use of tocolytic treatment, administration of prenatal corticotherapy,&#xD;
time between the last injection of corticosteroids and birth</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>composite Neonatal outcome</measure>
    <time_frame>At Birth</time_frame>
    <description>Assessed by :&#xD;
birth weight,&#xD;
Apgar score at 5 minutes,&#xD;
arterial cord pH,&#xD;
transfer to neonatology unit or neonatal intensive care,&#xD;
death,&#xD;
In case of transfer neonatal unit or neonatal intensive care : duration of hospitalization, use of respiratory assistance</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>composite Obstetric outcome</measure>
    <time_frame>At Delivery</time_frame>
    <description>Assessed by :&#xD;
pregnancy term,&#xD;
way to start labor (spontaneous, induction, caesarean before labor)&#xD;
duration of labor,&#xD;
maternal fever,&#xD;
antibiotics during labor,&#xD;
mode of delivery,&#xD;
indications of cesarean</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">238</enrollment>
  <condition>Preterm Labor (24 GA - 32 GA)</condition>
  <arm_group>
    <arm_group_label>Non pregnant women</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Healthy pregnancy : women 15-16 weeks of gestation, at 35-36 weeks of gestation, and &gt;37 weeks of gestation and planed cesarean prior labor</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Preterm Labor</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Pregnant women admitted for preterm labor</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Healthy pregnancy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Healthy pregnancy : women 15-16 weeks of gestation, at 35-36 weeks of gestation, and &gt;37 weeks of gestation and planed cesarean prior labor</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Cervicovaginal swab</intervention_name>
    <description>Sample of cervicovaginal secretions made by the surgical team using a sterile swab introduced directly into the posterior fornix of vagina for one minute during the insertion of the urinary catheter</description>
    <arm_group_label>Healthy pregnancy</arm_group_label>
    <arm_group_label>Non pregnant women</arm_group_label>
    <arm_group_label>Preterm Labor</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        - Singleton pregnancy, monitored in Port Royal or secondarily transferred, between 24 and&#xD;
        32 GA. Hospitalization for preterm labor (cervix &lt; 25 mm at transvaginal cervical&#xD;
        ultrasound) or -Singleton pregnancy, monitered in Port Royal between 15-16 weeks of&#xD;
        gestation, without complication.&#xD;
&#xD;
        or - Singleton pregnancy, monitered in Port Royal between 35-36 weeks of gestation, without&#xD;
        complication.&#xD;
&#xD;
        or - Healthy woman, no pregnancy.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Minor&#xD;
&#xD;
          -  Not affiliated to health insurance&#xD;
&#xD;
          -  Persons under guardianship or judicial protection&#xD;
&#xD;
          -  Infection with HIV, Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV)&#xD;
&#xD;
          -  Diabetes or chronic inflammatory disease&#xD;
&#xD;
          -  Carrier of B streptococcus&#xD;
&#xD;
          -  Cervical strapping&#xD;
&#xD;
          -  Fetus with chromosomal abnormalities&#xD;
&#xD;
          -  Infections&#xD;
&#xD;
          -  Premature rupture of membrane&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Celine MEHATS, PhD</last_name>
    <role>Study Director</role>
    <affiliation>INSERM U1016 - Cochin Hospital Public Hospitals of Paris</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Maternité Port Royal-Cochin</name>
      <address>
        <city>Paris</city>
        <zip>75014</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <reference>
    <citation>Larroque B, Ancel PY, Marret S, Marchand L, Andre M, Arnaud C, Pierrat V, Roze JC, Messer J, Thiriez G, Burguet A, Picaud JC, Breart G, Kaminski M; EPIPAGE Study group. Neurodevelopmental disabilities and special care of 5-year-old children born before 33 weeks of gestation (the EPIPAGE study): a longitudinal cohort study. Lancet. 2008 Mar 8;371(9615):813-20. doi: 10.1016/S0140-6736(08)60380-3.</citation>
    <PMID>18328928</PMID>
  </reference>
  <reference>
    <citation>McLaren J, Malak TM, Bell SC. Structural characteristics of term human fetal membranes prior to labour: identification of an area of altered morphology overlying the cervix. Hum Reprod. 1999 Jan;14(1):237-41. doi: 10.1093/humrep/14.1.237.</citation>
    <PMID>10374127</PMID>
  </reference>
  <reference>
    <citation>Malak TM, Bell SC. Structural characteristics of term human fetal membranes: a novel zone of extreme morphological alteration within the rupture site. Br J Obstet Gynaecol. 1994 May;101(5):375-86. doi: 10.1111/j.1471-0528.1994.tb11908.x.</citation>
    <PMID>8018607</PMID>
  </reference>
  <verification_date>June 2018</verification_date>
  <study_first_submitted>August 7, 2014</study_first_submitted>
  <study_first_submitted_qc>August 25, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 26, 2014</study_first_posted>
  <last_update_submitted>June 15, 2018</last_update_submitted>
  <last_update_submitted_qc>June 15, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">June 18, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Preterm labor</keyword>
  <keyword>cervicovaginal secretions</keyword>
  <keyword>markers of fetal membranes remodelling</keyword>
  <keyword>Multiplex test</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <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/NCT02225717
org study id: P140502
nct id: NCT02225717
lead sponsor: 
has dmc: No
The investigators project aims to identify, in pregnant women, discriminating molecules to
      allow an early detection of women who will spontaneously deliver prematurely, suitable in
      routine clinical practice.

      Human parturition is tightly correlated with hormonal changes at the maternal-fetal interface
      during pregnancy, that may control cell interactions and fetal membranes (the water bag)
      remodelling. Precocious remodelling may lead to a premature onset of labor, associated or not
      with premature rupture of membrane whether the cause is infectious or not.

      In this regard, remodelled fetal membranes overlying the cervix may discharge signals that
      could be detectable in cervico-vaginal fluids and serve as biomarkers of the imminence of
      delivery. Such information on delivery timing may be of great importance for an adequate
      prediction that would change drastically the management of threatening preterm delivery.
Prematurity is a major Public Health concern in developed countries, since it is the first
      cause of perinatal morbi-mortality and of cerebral palsy in early childhood. Premature birth
      rate has risen by 36 percent over the last 25 years to reach 7.2% in 2010 in France.
      Antenatal corticosteroids administration before 34 weeks and in utero transfer in
      high-qualified maternity wards are ones of the rare antenatal therapies recommended to
      improve neonatal complications of preterm delivery. Early identification of women with high
      risk of preterm birth should be helpful to implement those prophylactic measures. Moreover
      discriminating true preterm labor (PTL) vs. symptoms of PTL in women, who will finally
      deliver at term, would reduce unnecessary hospitalizations and prescriptions.

      During human gestation, fetal membranes (the "water bag") encompass the amnion, facing the
      amniotic cavity, and the chorion, lining the maternal decidua and comprising trophoblast
      cells. Membranes usually remain intact until their spontaneous rupture, close to the first
      stage of labor at term. Often seen as a simple inert shell, with a role of "airbag" for the
      developing fetus, the membranes provide yet a large surface of interaction between maternal
      and fetal tissues and function as a transient endocrine organ with immune properties.

      Specific remodelling of the membranes is observed at term prior to delivery. During this
      remodelling, drastic changes in extracellular matrix occur, with the secretion of specific
      molecules. The investigators hypothesize that premature fetal membranes remodelling occurs
      weeks prior to actual birth and may be able to be detected in women at risk for preterm
      birth, i.e. presenting signs of PTL. This study investigates if the detection of fetal
      membranes remodelling in cervico-vaginal fluids can accurately identify those women at
      greatest risk for preterm birth. A prospective cohort of pregnant women will before 32 weeks
      of gestation with symptoms of preterm labor be enrolled. As negative controls, healthy
      pregnant women at 12-15 or 35-36 weeks of gestation or non-pregnant women will be recruited.
      As positive controls, healthy pregnant woman at term (over 38 weeks of gestation) will be
      enrolled. The main outcome assessed is preterm delivery.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Screening
masking: None (Open Label)
measure: Delivery
time frame: until Day 14
description: Assessed among patients in preterm labor between 24 - 32 GA
measure: Delivery before 34 GA
time frame: until Day 14
description: Assessed among patients in preterm labor between 24 - 32 GA
measure: composite Prenatal maternal care
time frame: until Delivery
description: Assessed by :
number of hospitalization,
total duration of hospitalization for preterm labor,
use of tocolytic treatment, administration of prenatal corticotherapy,
time between the last injection of corticosteroids and birth
measure: composite Neonatal outcome
time frame: At Birth
description: Assessed by :
birth weight,
Apgar score at 5 minutes,
arterial cord pH,
transfer to neonatology unit or neonatal intensive care,
death,
In case of transfer neonatal unit or neonatal intensive care : duration of hospitalization, use of respiratory assistance
measure: composite Obstetric outcome
time frame: At Delivery
description: Assessed by :
pregnancy term,
way to start labor (spontaneous, induction, caesarean before labor)
duration of labor,
maternal fever,
antibiotics during labor,
mode of delivery,
indications of cesarean
arm group label: Non pregnant women
arm group type: Experimental
description: Healthy pregnancy : women 15-16 weeks of gestation, at 35-36 weeks of gestation, and >37 weeks of gestation and planed cesarean prior labor
arm group label: Preterm Labor
arm group type: Experimental
description: Pregnant women admitted for preterm labor
arm group label: Healthy pregnancy
arm group type: Experimental
description: Healthy pregnancy : women 15-16 weeks of gestation, at 35-36 weeks of gestation, and >37 weeks of gestation and planed cesarean prior labor
intervention type: Procedure
intervention name: Cervicovaginal swab
description: Sample of cervicovaginal secretions made by the surgical team using a sterile swab introduced directly into the posterior fornix of vagina for one minute during the insertion of the urinary catheter
arm group label: Healthy pregnancy
arm group label: Non pregnant women
arm group label: Preterm Labor
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Celine MEHATS, PhD
role: Study Director
affiliation: INSERM U1016 - Cochin Hospital Public Hospitals of Paris
facility: 
country: France
citation: Larroque B, Ancel PY, Marret S, Marchand L, Andre M, Arnaud C, Pierrat V, Roze JC, Messer J, Thiriez G, Burguet A, Picaud JC, Breart G, Kaminski M; EPIPAGE Study group. Neurodevelopmental disabilities and special care of 5-year-old children born before 33 weeks of gestation (the EPIPAGE study): a longitudinal cohort study. Lancet. 2008 Mar 8;371(9615):813-20. doi: 10.1016/S0140-6736(08)60380-3.
PMID: 18328928
citation: McLaren J, Malak TM, Bell SC. Structural characteristics of term human fetal membranes prior to labour: identification of an area of altered morphology overlying the cervix. Hum Reprod. 1999 Jan;14(1):237-41. doi: 10.1093/humrep/14.1.237.
PMID: 10374127
citation: Malak TM, Bell SC. Structural characteristics of term human fetal membranes: a novel zone of extreme morphological alteration within the rupture site. Br J Obstet Gynaecol. 1994 May;101(5):375-86. doi: 10.1111/j.1471-0528.1994.tb11908.x.
PMID: 8018607
responsible party type: Sponsor
mesh term: Obstetric Labor, Premature