<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/NCT03289611</url>
  </required_header>
  <id_info>
    <org_study_id>P161101</org_study_id>
    <nct_id>NCT03289611</nct_id>
  </id_info>
  <brief_title>Preeclampsia Ratio (sFlt-1/PlGF)</brief_title>
  <acronym>PRECOG</acronym>
  <official_title>Preeclampsia Ratio (sFlt-1/PlGF) Evaluation for Clinical and Obstetrical Guidance</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Assistance Publique - Hôpitaux de Paris</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>INSERM CESP1018</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Assistance Publique - Hôpitaux de Paris</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 aim of the PRECOG study is to determine in a prospective interventional randomized study&#xD;
      whether the implementation of a predictive test based on the sFLT-1/PlGF ratio improves&#xD;
      perinatal care and reduces costs, in patients with suspected preeclampsia before 35 weeks of&#xD;
      gestation.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Preeclampsia is a hypertensive disorder of pregnancy associated with placental insufficiency&#xD;
      and is one of the major important of prematurity and maternal mortality worldwide. It&#xD;
      complicates 2 to 7% of pregnancies. It is currently considered that preeclampsia is&#xD;
      associated with maternal endothelial dysfunction induced by the release into the maternal&#xD;
      circulation of excess placental factors (such as sFLT-1 a soluble receptor for VEGF and&#xD;
      PlGF). There is currently no curative treatment, and only childbirth and delivery of the&#xD;
      placenta alleviate the mother's symptoms. Moreover, the evolution from case with mild&#xD;
      symptoms to a severe case of preeclampsia is often is often rapid and difficult to&#xD;
      anticipate. Therefore, it is recommended to manage patients with preeclampsia in hospital and&#xD;
      cases of suspected preeclampsia are usually admitted in prenatal units. Each year thousands&#xD;
      of patients are hospitalized for surveillance and blood/urine analysis to rule out the&#xD;
      diagnosis of preeclampsia. A biological test to predict preeclampsia would therefore be of&#xD;
      particular interest in order to:&#xD;
&#xD;
        -  identify patients without preeclampsia and therefore void costs and iatrogenic&#xD;
           complications related to unnecessary hospitalization&#xD;
&#xD;
        -  identify patients at high risk of maternal and perinatal complications in order to&#xD;
           anticipate in utero transfer, optimize maternal and fetal surveillance and administrate&#xD;
           steroids.&#xD;
&#xD;
      It has recently been demonstrated that sFLT-1 and PlGF have a high predictive value for the&#xD;
      diagnosis and the prediction of preeclampsia, but the interest of introducing these markers&#xD;
      in clinical practice has not been demonstrated yet. The diagnostic and predictive value of&#xD;
      the sFlt-1/PlGF ratio in patients at risk of placenta-related disorders has been shown in the&#xD;
      recent literature and estimation of the sFlt-1/PlGF ratio has become an additional tool in&#xD;
      the management of these disorders, primarily PE. This ratio can distinguish the patients that&#xD;
      develop maternal or perinatal complications in the next 7-14 days from those with&#xD;
      uncomplicated pregnancy. Women with an sFlt-1/PlGF ratio&lt;38 do not have PE at the time of the&#xD;
      test and in all likelihood will not develop PE for at least 1week; it is thereby of great&#xD;
      value for reassuring the clinician and the patient. Up to 80% of patients are supposed to be&#xD;
      in this patient group; therefore, clinicians are able to exclude the majority of patients and&#xD;
      focus on those who need more attention and care. On contrary women with a sFlt-1/PlGF ratio &gt;&#xD;
      38 and more specifically those with a ratio over 85 are highly likely to develop preeclampsia&#xD;
      and should be managed according to local practice/guidelines. Thus the use of such predictive&#xD;
      tool appear very promising but its interest has not been demonstrated in prospective&#xD;
      intervention studies.&#xD;
&#xD;
      The aim of the PRECOG study is to determine in a prospective interventional randomized study&#xD;
      whether the implementation of a predictive test based on the sFLT-1/PlGF ratio improves&#xD;
      perinatal care and reduces costs, in patients with suspected preeclampsia before 35 WG.&#xD;
      costs, in patients with suspected preeclampsia before 35 WG.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 26, 2018</start_date>
  <completion_date type="Actual">August 27, 2020</completion_date>
  <primary_completion_date type="Actual">August 27, 2020</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Health Services Research</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>number of patients hospitalised for more than 24 hours</measure>
    <time_frame>up to 12 weeks</time_frame>
    <description>Duration in hours, from admission to discharge from hospital at initial hospitalisation</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Maternal and fetal morbidity</measure>
    <time_frame>up to 13 weeks</time_frame>
    <description>severe preeclampsia, eclampsia, HELLP syndrome, Disseminated intravascular coagulation, abruptio placenta, delivery before 34 WA, IUGR&lt; 3°P, Fetal death</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maternal morbidity</measure>
    <time_frame>up to 13 weeks</time_frame>
    <description>High blood pressure, preeclampsia, caesarean section, postpartum hemorrhage&gt; 500 ml</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Severe Maternal morbidity (Composite outcome )</measure>
    <time_frame>up to 13 weeks</time_frame>
    <description>eclampsia, HELLP syndrome, Disseminated intravascular coagulation, Abruption placenta</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of days between randomisation and delivery</measure>
    <time_frame>up to 12 weeks</time_frame>
    <description>Number of days between randomisation and delivery</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mode of delivery</measure>
    <time_frame>At delivery</time_frame>
    <description>Cesarean, vaginal delivery</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Gestational age</measure>
    <time_frame>at delivery</time_frame>
    <description>Gestational age at delivery</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Birth weight centile</measure>
    <time_frame>At delivery</time_frame>
    <description>Centile of birth weight</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fetal death</measure>
    <time_frame>up to 13 weeks</time_frame>
    <description>Fetal death diagnosed at ultrasound before delivery</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Prematurity before 37 WG</measure>
    <time_frame>up to 13 weeks</time_frame>
    <description>Delivery before 37 WG + 0 days</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Prematurity before 34 WG</measure>
    <time_frame>Delivery</time_frame>
    <description>Delivery before 34 WG + 0 days</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Prematurity before 32 WG</measure>
    <time_frame>Delivery</time_frame>
    <description>Delivery before 32 WG + 0 days</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Perinatal morbidity (Composite outcome)</measure>
    <time_frame>At delivery</time_frame>
    <description>prematurity, birth weight &lt;10 ° P</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Severe Perinatal morbidity (Composite outcome)</measure>
    <time_frame>At delivery</time_frame>
    <description>perinatal mortality, prematurity &lt;34 SA, birth weight &lt;3 ° P</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Costs</measure>
    <time_frame>up to 14 weeks</time_frame>
    <description>direct costs of prenatal care, direct costs of neonatal care, total costs</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Satisfaction form</measure>
    <time_frame>Day 3 after delivery</time_frame>
    <description>Satisfaction concerning the management of pregnancy and duration of hospitalisation</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">84</enrollment>
  <condition>Preeclampsia</condition>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Usual management</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Experimental</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Ambulatory management if sFlt-1 / PlGF ratio is below 38 Usual management if sFlt-1/PlGF is between 38 and 85. If the ratio is &gt; 85, monitoring will be intensified and patient hospitalization will be continued</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>sFlt-1 / PlGF ratio</intervention_name>
    <description>Ambulatory management if sFlt-1 / PlGF ratio is below 38&#xD;
usual management if sFlt-1/PlGF is between 38 and 85.&#xD;
If the ratio is &gt; 85, monitoring will be intensified and patient hospitalization will be continued</description>
    <arm_group_label>Experimental</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Patient hospitalized for suspected preeclampsia between 24WG+ 0 days and 35WG + 6 days,&#xD;
&#xD;
        Patiente with at least one of the following criteria:&#xD;
&#xD;
          -  Arterial hypertension defined by systolic BP ≥ 140 mm Hg or diastolic blood pressure ≥&#xD;
             90 mm Hg&#xD;
&#xD;
          -  Proteinuria greater than 0.3g / 24h or 0.3g / l or ≥ 3+&#xD;
&#xD;
          -  Proteinuria / creatinine ratio ≥ 30 mg / mmol&#xD;
&#xD;
          -  Pain in the epigastric bar&#xD;
&#xD;
          -  Generalized edema&#xD;
&#xD;
          -  Hepatic cytolysis&gt; 1.5N&#xD;
&#xD;
          -  Thrombocytopenia &lt;150000 / mm3 Informed consent signed by both parties Non-opposition&#xD;
             was accepted by parental authority Age ≥ 18 years&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Diagnosis of preeclampsia (arterial pressure&gt; 140/90 and proteinuria&gt; 0.3g / 24h or urine&#xD;
        test&gt; 3+) or complete HELLP syndrome (Platelets &lt;100000 / mm3 and SGOT&gt; 2N and LDH and&#xD;
        collapsed Haptoglobin)&#xD;
&#xD;
        IUGR with absent or reverse diastolic umbilical flow&#xD;
&#xD;
        Fetal heart rate abnormalities&#xD;
&#xD;
        Gestational age &lt;24 WG and&gt; 35 WG&#xD;
&#xD;
        Multiple pregnancy&#xD;
&#xD;
        Patient without health insurance&#xD;
&#xD;
        Non-consent of patient&#xD;
&#xD;
        Minor patient&#xD;
&#xD;
        Congenital malformation&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jean GUIBOURDENCHE, MD, PhD</last_name>
    <role>Study Chair</role>
    <affiliation>Assistance Publique - Hôpitaux de Paris</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>CHU Cochin, Maternité Port Royal</name>
      <address>
        <city>Paris</city>
        <zip>75014</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <reference>
    <citation>Tsatsaris V, Goffin F, Munaut C, Brichant JF, Pignon MR, Noel A, Schaaps JP, Cabrol D, Frankenne F, Foidart JM. Overexpression of the soluble vascular endothelial growth factor receptor in preeclamptic patients: pathophysiological consequences. J Clin Endocrinol Metab. 2003 Nov;88(11):5555-63. doi: 10.1210/jc.2003-030528.</citation>
    <PMID>14602804</PMID>
  </reference>
  <reference>
    <citation>Sibiude J, Guibourdenche J, Dionne MD, Le Ray C, Anselem O, Serreau R, Goffinet F, Tsatsaris V. Placental growth factor for the prediction of adverse outcomes in patients with suspected preeclampsia or intrauterine growth restriction. PLoS One. 2012;7(11):e50208. doi: 10.1371/journal.pone.0050208. Epub 2012 Nov 28.</citation>
    <PMID>23209675</PMID>
  </reference>
  <reference>
    <citation>Zeisler H, Llurba E, Chantraine F, Vatish M, Staff AC, Sennstrom M, Olovsson M, Brennecke SP, Stepan H, Allegranza D, Dilba P, Schoedl M, Hund M, Verlohren S. Predictive Value of the sFlt-1:PlGF Ratio in Women with Suspected Preeclampsia. N Engl J Med. 2016 Jan 7;374(1):13-22. doi: 10.1056/NEJMoa1414838.</citation>
    <PMID>26735990</PMID>
  </reference>
  <verification_date>July 2021</verification_date>
  <study_first_submitted>September 4, 2017</study_first_submitted>
  <study_first_submitted_qc>September 20, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 21, 2017</study_first_posted>
  <last_update_submitted>July 31, 2021</last_update_submitted>
  <last_update_submitted_qc>July 31, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">August 3, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Preeclampsia</keyword>
  <keyword>pregnancy</keyword>
  <keyword>biomarkers</keyword>
  <keyword>prediction</keyword>
  <keyword>safety</keyword>
  <keyword>cost</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pre-Eclampsia</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/NCT03289611
org study id: P161101
nct id: NCT03289611
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The aim of the PRECOG study is to determine in a prospective interventional randomized study
      whether the implementation of a predictive test based on the sFLT-1/PlGF ratio improves
      perinatal care and reduces costs, in patients with suspected preeclampsia before 35 weeks of
      gestation.
Preeclampsia is a hypertensive disorder of pregnancy associated with placental insufficiency
      and is one of the major important of prematurity and maternal mortality worldwide. It
      complicates 2 to 7% of pregnancies. It is currently considered that preeclampsia is
      associated with maternal endothelial dysfunction induced by the release into the maternal
      circulation of excess placental factors (such as sFLT-1 a soluble receptor for VEGF and
      PlGF). There is currently no curative treatment, and only childbirth and delivery of the
      placenta alleviate the mother's symptoms. Moreover, the evolution from case with mild
      symptoms to a severe case of preeclampsia is often is often rapid and difficult to
      anticipate. Therefore, it is recommended to manage patients with preeclampsia in hospital and
      cases of suspected preeclampsia are usually admitted in prenatal units. Each year thousands
      of patients are hospitalized for surveillance and blood/urine analysis to rule out the
      diagnosis of preeclampsia. A biological test to predict preeclampsia would therefore be of
      particular interest in order to:

        -  identify patients without preeclampsia and therefore void costs and iatrogenic
           complications related to unnecessary hospitalization

        -  identify patients at high risk of maternal and perinatal complications in order to
           anticipate in utero transfer, optimize maternal and fetal surveillance and administrate
           steroids.

      It has recently been demonstrated that sFLT-1 and PlGF have a high predictive value for the
      diagnosis and the prediction of preeclampsia, but the interest of introducing these markers
      in clinical practice has not been demonstrated yet. The diagnostic and predictive value of
      the sFlt-1/PlGF ratio in patients at risk of placenta-related disorders has been shown in the
      recent literature and estimation of the sFlt-1/PlGF ratio has become an additional tool in
      the management of these disorders, primarily PE. This ratio can distinguish the patients that
      develop maternal or perinatal complications in the next 7-14 days from those with
      uncomplicated pregnancy. Women with an sFlt-1/PlGF ratio<38 do not have PE at the time of the
      test and in all likelihood will not develop PE for at least 1week; it is thereby of great
      value for reassuring the clinician and the patient. Up to 80% of patients are supposed to be
      in this patient group; therefore, clinicians are able to exclude the majority of patients and
      focus on those who need more attention and care. On contrary women with a sFlt-1/PlGF ratio >
      38 and more specifically those with a ratio over 85 are highly likely to develop preeclampsia
      and should be managed according to local practice/guidelines. Thus the use of such predictive
      tool appear very promising but its interest has not been demonstrated in prospective
      intervention studies.

      The aim of the PRECOG study is to determine in a prospective interventional randomized study
      whether the implementation of a predictive test based on the sFLT-1/PlGF ratio improves
      perinatal care and reduces costs, in patients with suspected preeclampsia before 35 WG.
      costs, in patients with suspected preeclampsia before 35 WG.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Health Services Research
masking: None (Open Label)
measure: number of patients hospitalised for more than 24 hours
time frame: up to 12 weeks
description: Duration in hours, from admission to discharge from hospital at initial hospitalisation
measure: Maternal and fetal morbidity
time frame: up to 13 weeks
description: severe preeclampsia, eclampsia, HELLP syndrome, Disseminated intravascular coagulation, abruptio placenta, delivery before 34 WA, IUGR< 3°P, Fetal death
measure: Maternal morbidity
time frame: up to 13 weeks
description: High blood pressure, preeclampsia, caesarean section, postpartum hemorrhage> 500 ml
measure: Severe Maternal morbidity (Composite outcome )
time frame: up to 13 weeks
description: eclampsia, HELLP syndrome, Disseminated intravascular coagulation, Abruption placenta
measure: Number of days between randomisation and delivery
time frame: up to 12 weeks
description: Number of days between randomisation and delivery
measure: Mode of delivery
time frame: At delivery
description: Cesarean, vaginal delivery
measure: Gestational age
time frame: at delivery
description: Gestational age at delivery
measure: Birth weight centile
time frame: At delivery
description: Centile of birth weight
measure: Fetal death
time frame: up to 13 weeks
description: Fetal death diagnosed at ultrasound before delivery
measure: Prematurity before 37 WG
time frame: up to 13 weeks
description: Delivery before 37 WG + 0 days
measure: Prematurity before 34 WG
time frame: Delivery
description: Delivery before 34 WG + 0 days
measure: Prematurity before 32 WG
time frame: Delivery
description: Delivery before 32 WG + 0 days
measure: Perinatal morbidity (Composite outcome)
time frame: At delivery
description: prematurity, birth weight <10 ° P
measure: Severe Perinatal morbidity (Composite outcome)
time frame: At delivery
description: perinatal mortality, prematurity <34 SA, birth weight <3 ° P
measure: Costs
time frame: up to 14 weeks
description: direct costs of prenatal care, direct costs of neonatal care, total costs
measure: Satisfaction form
time frame: Day 3 after delivery
description: Satisfaction concerning the management of pregnancy and duration of hospitalisation
arm group label: Control
arm group type: No Intervention
description: Usual management
arm group label: Experimental
arm group type: Experimental
description: Ambulatory management if sFlt-1 / PlGF ratio is below 38 Usual management if sFlt-1/PlGF is between 38 and 85. If the ratio is > 85, monitoring will be intensified and patient hospitalization will be continued
intervention type: Biological
intervention name: sFlt-1 / PlGF ratio
description: Ambulatory management if sFlt-1 / PlGF ratio is below 38
usual management if sFlt-1/PlGF is between 38 and 85.
If the ratio is > 85, monitoring will be intensified and patient hospitalization will be continued
arm group label: Experimental
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jean GUIBOURDENCHE, MD, PhD
role: Study Chair
affiliation: Assistance Publique - Hôpitaux de Paris
facility: 
country: France
citation: Tsatsaris V, Goffin F, Munaut C, Brichant JF, Pignon MR, Noel A, Schaaps JP, Cabrol D, Frankenne F, Foidart JM. Overexpression of the soluble vascular endothelial growth factor receptor in preeclamptic patients: pathophysiological consequences. J Clin Endocrinol Metab. 2003 Nov;88(11):5555-63. doi: 10.1210/jc.2003-030528.
PMID: 14602804
citation: Sibiude J, Guibourdenche J, Dionne MD, Le Ray C, Anselem O, Serreau R, Goffinet F, Tsatsaris V. Placental growth factor for the prediction of adverse outcomes in patients with suspected preeclampsia or intrauterine growth restriction. PLoS One. 2012;7(11):e50208. doi: 10.1371/journal.pone.0050208. Epub 2012 Nov 28.
PMID: 23209675
citation: Zeisler H, Llurba E, Chantraine F, Vatish M, Staff AC, Sennstrom M, Olovsson M, Brennecke SP, Stepan H, Allegranza D, Dilba P, Schoedl M, Hund M, Verlohren S. Predictive Value of the sFlt-1:PlGF Ratio in Women with Suspected Preeclampsia. N Engl J Med. 2016 Jan 7;374(1):13-22. doi: 10.1056/NEJMoa1414838.
PMID: 26735990
responsible party type: Sponsor
mesh term: Pre-Eclampsia