<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/NCT03815110</url>
  </required_header>
  <id_info>
    <org_study_id>Pro00055135</org_study_id>
    <nct_id>NCT03815110</nct_id>
  </id_info>
  <brief_title>Preeclampsia Risk Assessment: Evaluation of Cut-offs to Improve Stratification</brief_title>
  <acronym>PRAECIS</acronym>
  <official_title>Preeclampsia Risk Assessment: Evaluation of Cut-offs to Improve Stratification</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Cedars-Sinai Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>ThermoFisher Scientific Brahms Biomarkers France</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Cedars-Sinai Medical Center</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 purpose of this study is to&#xD;
&#xD;
        1. Identify a cut-off for the ratio of the serum proteins soluble FMS-like Tyrosine Kinase&#xD;
           1 (sFLT-1) and placental growth factor (PlGF) that identifies women will who develop&#xD;
           preeclampsia with severe features within 2 weeks of testing (clinically positive) from&#xD;
           those who do not develop preeclampsia with severe features within 2 weeks of testing&#xD;
           (clinically negative) among preterm pregnant women with hypertensive disorders of&#xD;
           pregnancy.&#xD;
&#xD;
           And&#xD;
&#xD;
        2. To validate the cut-off the ratio of sFLT-1 and PlGF and to validate the performance of&#xD;
           the automated assays used to find the cut-off. Test performance includes positive&#xD;
           predictive value, negative predictive value, sensitivity, and specificity.&#xD;
&#xD;
      Subjects will provide blood, urine, and saliva samples at the time of enrollment. Samples&#xD;
      will be frozen for batch assessment of sFLT-1 and PlGF levels by automated assays.&#xD;
      Clinicians, subjects, and researchers will be blinded to protein level assessment, therefore&#xD;
      assay results will not affect clinical management.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Preeclampsia is a leading cause of maternal and fetal morbidity and mortality in the US, and&#xD;
      affects about 5% of pregnancies. Despite its morbidity, preeclampsia is challenging to&#xD;
      distinguish from worsening chronic hypertension or gestational hypertension. Furthermore, it&#xD;
      is challenging to identify who among those with hypertensive disorders of pregnancy will&#xD;
      develop preeclampsia with severe features, including kidney, liver, pulmonary, or cerebral&#xD;
      injury. The only definitive treatment is delivery of the placenta, and therefore the fetus,&#xD;
      which can lead to severe morbidity and mortality to the neonate if delivery is very&#xD;
      premature. New methods of risk stratification are needed to identify who among women with&#xD;
      hypertensive disorders of pregnancy are at risk of developing preeclampsia with severe&#xD;
      features in order to allocate resources (e.g. betamethasone and magnesium for fetal&#xD;
      neuroprotection) accordingly.&#xD;
&#xD;
      Several serum proteins (sFLT-1 and PlGF) correlate well with the development of preeclampsia,&#xD;
      particularly with preeclampsia with severe features, and may be used to predict the&#xD;
      development of preeclampsia with severe features within a certain timeframe. The goal of this&#xD;
      study is to identify a cut-off of the sFLT-1/PlGF ratio using automated assays that&#xD;
      differentiates women who will develop preeclampsia with severe features from those who will&#xD;
      not among women with hypertensive disorders of pregnancy within 2 weeks of testing. The&#xD;
      secondary outcomes include time to delivery, the performance of the cut-off to predict&#xD;
      adverse maternal and adverse fetal outcomes, and a comparison of the performance of the&#xD;
      cut-off with clinical and laboratory factors per American College of Obstetricians and&#xD;
      Gynecologists (ACOG) guidelines. Investigators will also look at the levels of sFLT-1 and&#xD;
      PlGF in the urine and the saliva to determine if they correlate well with serum levels and&#xD;
      may provide a less invasive alternative to serum samples.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 20, 2018</start_date>
  <completion_date type="Actual">October 1, 2022</completion_date>
  <primary_completion_date type="Actual">November 19, 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>Derivation and Performance of Cut-off for sFLT-1/PlGF Ratio (Serum)</measure>
    <time_frame>2 weeks</time_frame>
    <description>Identification of the cut-off and performance (sensitivity, specificity, positive predictive value, and negative predictive value) for the sFLT-1/PlGF ratio as determined by automated assays that enable differentiation of those women with a hypertensive disorder of pregnancy who develop preeclampsia with severe features from those who do not develop preeclampsia within 2 weeks of testing.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Validation of Cut-off and Performance of sFLT-1/PlGF Ratio as Defined in Derivation Cohort (Serum)</measure>
    <time_frame>2 weeks</time_frame>
    <description>Validation of the performance (sensitivity, specificity, positive predictive value, negative predictive value) of the cut-off of the sFLT-1/PlGF ratio differentiating the development of preeclampsia with severe features within 2 weeks after testing as determined by the independent Derivation cohort.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Performance in Determining the Risk for Adverse Maternal Outcomes</measure>
    <time_frame>2 weeks</time_frame>
    <description>Performance (sensitivity, specificity, positive predictive value, negative predictive value) of the sFLT-1/PlGF cut-off identified and validated per primary endpoint in determining the risk of adverse maternal outcomes within 2 weeks after testing.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Performance in Determining the Risk for Adverse Fetal/Neonatal Outcomes</measure>
    <time_frame>4 weeks</time_frame>
    <description>Performance (sensitivity, specificity, positive predictive value, negative predictive value) of the sFLT-1/PlGF cut-off identified and validated per primary endpoint in determining the risk of adverse fetal/neonatal outcomes within 2 weeks after testing.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Performance As Compared to ACOG-Guidelines</measure>
    <time_frame>2 years</time_frame>
    <description>Performance of the sFLT-1/PlGF ratio versus the performance of clinical and laboratory factors per ACOG guidelines in predicting maternal development of preeclampsia with severe features.&#xD;
ACOG guidelines in predicting the development of preeclampsia include,&#xD;
systolic blood pressure of 140 mm Hg or more or diastolic blood pressure of 90 mm HG or more on at least 2 occasions at least 4 hours apart&#xD;
300 mg or more of protein per 24 hour urine collection&#xD;
Protein/creatinine ration of 0.3 mg/dL or more&#xD;
Urine dipstick reading of 2+&#xD;
Uric acid greater than 5 mg/dL</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Performance of sFLT-1/PlGF &amp; ACOG Guidelines</measure>
    <time_frame>2 years</time_frame>
    <description>Performance of the algorithm combining the sFLT-1/PlGF ratio PLUS clinical and laboratory factors per ACOG guidelines in predicting maternal development of preeclampsia with severe features.&#xD;
ACOG guidelines in predicting the development of preeclampsia include,&#xD;
systolic blood pressure of 140 mm Hg or more or diastolic blood pressure of 90 mm HG or more on at least 2 occasions at least 4 hours apart&#xD;
300 mg or more of protein per 24 hour urine collection&#xD;
Protein/creatinine ration of 0.3 mg/dL or more&#xD;
Urine dipstick reading of 2+&#xD;
Uric acid greater than 5 mg/dL</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Delivery</measure>
    <time_frame>2 years</time_frame>
    <description>Time to delivery in women whose sFLT-1/PlGF ratio is above the cut-off as identified per the primary objective compared to those whose sFLT-1/PlGF ratio is below that cut-off.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>sFLT-1 and PlGF Levels in Urine and Saliva</measure>
    <time_frame>2 years</time_frame>
    <description>Identification of levels of sFLT-1 (pg/ml) and PlGF (pg/ml) in urine and saliva specimens.</description>
  </secondary_outcome>
  <enrollment type="Actual">1050</enrollment>
  <condition>Preeclampsia and Eclampsia</condition>
  <condition>Preeclampsia Severe</condition>
  <condition>Gestational Hypertension</condition>
  <condition>Chronic Hypertension in Obstetric Context</condition>
  <condition>Superimposed Pre-Eclampsia</condition>
  <condition>Preeclampsia Mild</condition>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Serum Sample (10 mL) Plasma Sample (10 mL) Urine Collection Saliva Swab&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        The study population includes women with singleton pregnancies at 23+0 to 34+6/7 weeks&#xD;
        gestational age who are hospitalized with (or develop while hospitalized) a hypertensive&#xD;
        disorder of pregnancy. Minors and patients who have received intravenous heparin within 24&#xD;
        hours of enrollment or who have participated in a therapeutic interventional study in the&#xD;
        last 30 days will be excluded.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Signed informed consent in a pregnant woman ≥ 18 years of age.&#xD;
&#xD;
          -  Gestational age 23+0 to 34+6/7 weeks&#xD;
&#xD;
          -  Singleton pregnancy&#xD;
&#xD;
          -  Hospitalized with (or develop while hospitalized) a hypertensive disorder of pregnancy&#xD;
             (preeclampsia, chronic hypertension with or without superimposed preeclampsia or&#xD;
             gestational hypertension) as defined by ACOG guidelines.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  1. Patients who have received intravenous heparin within 24 hours of enrollment. Low&#xD;
             dose subcutaneous heparin or low molecular weight heparin (LMWH) for prophylaxis of&#xD;
             deep venous thrombosis (DVT) is permitted.&#xD;
&#xD;
          -  Patients who are currently participating in another clinical trial to evaluate a new&#xD;
             therapeutic intervention or who have participated in another such trial in the&#xD;
             previous 30 days.&#xD;
&#xD;
          -  Multiple gestations.&#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>Ananth Karumanchi, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Cedars-Sinai Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Cedars-Sinai Medical Center</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90048</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sharp Mary Birch Hospital for Women &amp; Newborns</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92123</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UC San Francisco Medical Center</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94158</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Torrance Memorial Medical Center</name>
      <address>
        <city>Torrance</city>
        <state>California</state>
        <zip>90505</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of South Florida</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33606</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Chicago Medical Center</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60637</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Northshore</name>
      <address>
        <city>Evanston</city>
        <state>Illinois</state>
        <zip>60201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MedStar Health</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21237</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Johns Hopkins University Medical Center</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21287</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tufts Medical Center</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02111</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Beth Israel Deaconess Medical Center</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Massachusetts Memorial Medical Center</name>
      <address>
        <city>Worcester</city>
        <state>Massachusetts</state>
        <zip>01605</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of North Carolina Medical Center- Chapel Hill</name>
      <address>
        <city>Chapel Hill</city>
        <state>North Carolina</state>
        <zip>27599-7516</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ohio State University Wexner Medical Center</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Miami Valley Hospital</name>
      <address>
        <city>Dayton</city>
        <state>Ohio</state>
        <zip>45409</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lehigh Valley Health Network</name>
      <address>
        <city>Allentown</city>
        <state>Pennsylvania</state>
        <zip>18102</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Baylor College of Medicine</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Utah</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84132</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Hypertension in pregnancy. Report of the American College of Obstetricians and Gynecologists' Task Force on Hypertension in Pregnancy. Obstet Gynecol. 2013 Nov;122(5):1122-1131. doi: 10.1097/01.AOG.0000437382.03963.88. No abstract available.</citation>
    <PMID>24150027</PMID>
  </reference>
  <reference>
    <citation>Levine RJ, Maynard SE, Qian C, Lim KH, England LJ, Yu KF, Schisterman EF, Thadhani R, Sachs BP, Epstein FH, Sibai BM, Sukhatme VP, Karumanchi SA. Circulating angiogenic factors and the risk of preeclampsia. N Engl J Med. 2004 Feb 12;350(7):672-83. doi: 10.1056/NEJMoa031884. Epub 2004 Feb 5.</citation>
    <PMID>14764923</PMID>
  </reference>
  <reference>
    <citation>Sunderji S, Gaziano E, Wothe D, Rogers LC, Sibai B, Karumanchi SA, Hodges-Savola C. Automated assays for sVEGF R1 and PlGF as an aid in the diagnosis of preterm preeclampsia: a prospective clinical study. Am J Obstet Gynecol. 2010 Jan;202(1):40.e1-7. doi: 10.1016/j.ajog.2009.07.025. Epub 2009 Sep 17.</citation>
    <PMID>19762001</PMID>
  </reference>
  <reference>
    <citation>Engels T, Pape J, Schoofs K, Henrich W, Verlohren S. Automated measurement of sFlt1, PlGF and sFlt1/PlGF ratio in differential diagnosis of hypertensive pregnancy disorders. Hypertens Pregnancy. 2013 Nov;32(4):459-73. doi: 10.3109/10641955.2013.827205. Epub 2013 Aug 19.</citation>
    <PMID>23957293</PMID>
  </reference>
  <reference>
    <citation>Verlohren S, Herraiz I, Lapaire O, Schlembach D, Moertl M, Zeisler H, Calda P, Holzgreve W, Galindo A, Engels T, Denk B, Stepan H. The sFlt-1/PlGF ratio in different types of hypertensive pregnancy disorders and its prognostic potential in preeclamptic patients. Am J Obstet Gynecol. 2012 Jan;206(1):58.e1-8. doi: 10.1016/j.ajog.2011.07.037. Epub 2011 Jul 30.</citation>
    <PMID>22000672</PMID>
  </reference>
  <reference>
    <citation>Rana S, Powe CE, Salahuddin S, Verlohren S, Perschel FH, Levine RJ, Lim KH, Wenger JB, Thadhani R, Karumanchi SA. Angiogenic factors and the risk of adverse outcomes in women with suspected preeclampsia. Circulation. 2012 Feb 21;125(7):911-9. doi: 10.1161/CIRCULATIONAHA.111.054361. Epub 2012 Jan 18.</citation>
    <PMID>22261192</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>November 2022</verification_date>
  <study_first_submitted>January 17, 2019</study_first_submitted>
  <study_first_submitted_qc>January 21, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 24, 2019</study_first_posted>
  <last_update_submitted>November 23, 2022</last_update_submitted>
  <last_update_submitted_qc>November 23, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">November 28, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Cedars-Sinai Medical Center</investigator_affiliation>
    <investigator_full_name>S Ananth Karumanchi</investigator_full_name>
    <investigator_title>Lead Principal Investigator</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pre-Eclampsia</mesh_term>
    <mesh_term>Eclampsia</mesh_term>
    <mesh_term>Hypertension, Pregnancy-Induced</mesh_term>
    <mesh_term>Hypertension</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03815110
org study id: Pro00055135
nct id: NCT03815110
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The purpose of this study is to

        1. Identify a cut-off for the ratio of the serum proteins soluble FMS-like Tyrosine Kinase
           1 (sFLT-1) and placental growth factor (PlGF) that identifies women will who develop
           preeclampsia with severe features within 2 weeks of testing (clinically positive) from
           those who do not develop preeclampsia with severe features within 2 weeks of testing
           (clinically negative) among preterm pregnant women with hypertensive disorders of
           pregnancy.

           And

        2. To validate the cut-off the ratio of sFLT-1 and PlGF and to validate the performance of
           the automated assays used to find the cut-off. Test performance includes positive
           predictive value, negative predictive value, sensitivity, and specificity.

      Subjects will provide blood, urine, and saliva samples at the time of enrollment. Samples
      will be frozen for batch assessment of sFLT-1 and PlGF levels by automated assays.
      Clinicians, subjects, and researchers will be blinded to protein level assessment, therefore
      assay results will not affect clinical management.
Preeclampsia is a leading cause of maternal and fetal morbidity and mortality in the US, and
      affects about 5% of pregnancies. Despite its morbidity, preeclampsia is challenging to
      distinguish from worsening chronic hypertension or gestational hypertension. Furthermore, it
      is challenging to identify who among those with hypertensive disorders of pregnancy will
      develop preeclampsia with severe features, including kidney, liver, pulmonary, or cerebral
      injury. The only definitive treatment is delivery of the placenta, and therefore the fetus,
      which can lead to severe morbidity and mortality to the neonate if delivery is very
      premature. New methods of risk stratification are needed to identify who among women with
      hypertensive disorders of pregnancy are at risk of developing preeclampsia with severe
      features in order to allocate resources (e.g. betamethasone and magnesium for fetal
      neuroprotection) accordingly.

      Several serum proteins (sFLT-1 and PlGF) correlate well with the development of preeclampsia,
      particularly with preeclampsia with severe features, and may be used to predict the
      development of preeclampsia with severe features within a certain timeframe. The goal of this
      study is to identify a cut-off of the sFLT-1/PlGF ratio using automated assays that
      differentiates women who will develop preeclampsia with severe features from those who will
      not among women with hypertensive disorders of pregnancy within 2 weeks of testing. The
      secondary outcomes include time to delivery, the performance of the cut-off to predict
      adverse maternal and adverse fetal outcomes, and a comparison of the performance of the
      cut-off with clinical and laboratory factors per American College of Obstetricians and
      Gynecologists (ACOG) guidelines. Investigators will also look at the levels of sFLT-1 and
      PlGF in the urine and the saliva to determine if they correlate well with serum levels and
      may provide a less invasive alternative to serum samples.
observational model: Cohort
time perspective: Prospective
measure: Derivation and Performance of Cut-off for sFLT-1/PlGF Ratio (Serum)
time frame: 2 weeks
description: Identification of the cut-off and performance (sensitivity, specificity, positive predictive value, and negative predictive value) for the sFLT-1/PlGF ratio as determined by automated assays that enable differentiation of those women with a hypertensive disorder of pregnancy who develop preeclampsia with severe features from those who do not develop preeclampsia within 2 weeks of testing.
measure: Validation of Cut-off and Performance of sFLT-1/PlGF Ratio as Defined in Derivation Cohort (Serum)
time frame: 2 weeks
description: Validation of the performance (sensitivity, specificity, positive predictive value, negative predictive value) of the cut-off of the sFLT-1/PlGF ratio differentiating the development of preeclampsia with severe features within 2 weeks after testing as determined by the independent Derivation cohort.
measure: Performance in Determining the Risk for Adverse Maternal Outcomes
time frame: 2 weeks
description: Performance (sensitivity, specificity, positive predictive value, negative predictive value) of the sFLT-1/PlGF cut-off identified and validated per primary endpoint in determining the risk of adverse maternal outcomes within 2 weeks after testing.
measure: Performance in Determining the Risk for Adverse Fetal/Neonatal Outcomes
time frame: 4 weeks
description: Performance (sensitivity, specificity, positive predictive value, negative predictive value) of the sFLT-1/PlGF cut-off identified and validated per primary endpoint in determining the risk of adverse fetal/neonatal outcomes within 2 weeks after testing.
measure: Performance As Compared to ACOG-Guidelines
time frame: 2 years
description: Performance of the sFLT-1/PlGF ratio versus the performance of clinical and laboratory factors per ACOG guidelines in predicting maternal development of preeclampsia with severe features.
ACOG guidelines in predicting the development of preeclampsia include,
systolic blood pressure of 140 mm Hg or more or diastolic blood pressure of 90 mm HG or more on at least 2 occasions at least 4 hours apart
300 mg or more of protein per 24 hour urine collection
Protein/creatinine ration of 0.3 mg/dL or more
Urine dipstick reading of 2+
Uric acid greater than 5 mg/dL
measure: Performance of sFLT-1/PlGF & ACOG Guidelines
time frame: 2 years
description: Performance of the algorithm combining the sFLT-1/PlGF ratio PLUS clinical and laboratory factors per ACOG guidelines in predicting maternal development of preeclampsia with severe features.
ACOG guidelines in predicting the development of preeclampsia include,
systolic blood pressure of 140 mm Hg or more or diastolic blood pressure of 90 mm HG or more on at least 2 occasions at least 4 hours apart
300 mg or more of protein per 24 hour urine collection
Protein/creatinine ration of 0.3 mg/dL or more
Urine dipstick reading of 2+
Uric acid greater than 5 mg/dL
measure: Time to Delivery
time frame: 2 years
description: Time to delivery in women whose sFLT-1/PlGF ratio is above the cut-off as identified per the primary objective compared to those whose sFLT-1/PlGF ratio is below that cut-off.
measure: sFLT-1 and PlGF Levels in Urine and Saliva
time frame: 2 years
description: Identification of levels of sFLT-1 (pg/ml) and PlGF (pg/ml) in urine and saliva specimens.
Serum Sample (10 mL) Plasma Sample (10 mL) Urine Collection Saliva Swab
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Ananth Karumanchi, MD
role: Principal Investigator
affiliation: Cedars-Sinai Medical Center
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
citation: Hypertension in pregnancy. Report of the American College of Obstetricians and Gynecologists' Task Force on Hypertension in Pregnancy. Obstet Gynecol. 2013 Nov;122(5):1122-1131. doi: 10.1097/01.AOG.0000437382.03963.88. No abstract available.
PMID: 24150027
citation: Levine RJ, Maynard SE, Qian C, Lim KH, England LJ, Yu KF, Schisterman EF, Thadhani R, Sachs BP, Epstein FH, Sibai BM, Sukhatme VP, Karumanchi SA. Circulating angiogenic factors and the risk of preeclampsia. N Engl J Med. 2004 Feb 12;350(7):672-83. doi: 10.1056/NEJMoa031884. Epub 2004 Feb 5.
PMID: 14764923
citation: Sunderji S, Gaziano E, Wothe D, Rogers LC, Sibai B, Karumanchi SA, Hodges-Savola C. Automated assays for sVEGF R1 and PlGF as an aid in the diagnosis of preterm preeclampsia: a prospective clinical study. Am J Obstet Gynecol. 2010 Jan;202(1):40.e1-7. doi: 10.1016/j.ajog.2009.07.025. Epub 2009 Sep 17.
PMID: 19762001
citation: Engels T, Pape J, Schoofs K, Henrich W, Verlohren S. Automated measurement of sFlt1, PlGF and sFlt1/PlGF ratio in differential diagnosis of hypertensive pregnancy disorders. Hypertens Pregnancy. 2013 Nov;32(4):459-73. doi: 10.3109/10641955.2013.827205. Epub 2013 Aug 19.
PMID: 23957293
citation: Verlohren S, Herraiz I, Lapaire O, Schlembach D, Moertl M, Zeisler H, Calda P, Holzgreve W, Galindo A, Engels T, Denk B, Stepan H. The sFlt-1/PlGF ratio in different types of hypertensive pregnancy disorders and its prognostic potential in preeclamptic patients. Am J Obstet Gynecol. 2012 Jan;206(1):58.e1-8. doi: 10.1016/j.ajog.2011.07.037. Epub 2011 Jul 30.
PMID: 22000672
citation: Rana S, Powe CE, Salahuddin S, Verlohren S, Perschel FH, Levine RJ, Lim KH, Wenger JB, Thadhani R, Karumanchi SA. Angiogenic factors and the risk of adverse outcomes in women with suspected preeclampsia. Circulation. 2012 Feb 21;125(7):911-9. doi: 10.1161/CIRCULATIONAHA.111.054361. Epub 2012 Jan 18.
PMID: 22261192
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: Principal Investigator
investigator affiliation: Cedars-Sinai Medical Center
investigator full name: S Ananth Karumanchi
investigator title: Lead Principal Investigator
mesh term: Pre-Eclampsia
mesh term: Eclampsia
mesh term: Hypertension, Pregnancy-Induced
mesh term: Hypertension
sharing ipd: Undecided