<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/NCT04412681</url>
  </required_header>
  <id_info>
    <org_study_id>PEprotocol</org_study_id>
    <nct_id>NCT04412681</nct_id>
  </id_info>
  <brief_title>Precision Medicine for Prediction &amp; Prevention of Early Pre-eclampsia</brief_title>
  <official_title>Using Precision Medicine for the Prediction and Prevention of Early Pre-eclampsia: A Feasibility Study at Sunnybrook Health Sciences Centre.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sunnybrook Health Sciences Centre</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>North York General Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Sunnybrook Health Sciences Centre</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>
      This study aims to evaluate the feasibility of implementing a clinical model for precision&#xD;
      screening of early pre-eclampsia into the current prenatal screening service at Sunnybrook&#xD;
      Health Sciences Center (SHSC).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Pre-eclampsia (PE) represents a pregnancy-specific systemic disorder that affects 3-8% of all&#xD;
      pregnancies. In developed countries PE is considered a major public health problem&#xD;
      responsible for severe maternal complications such as coagulopathy, renal and liver failure,&#xD;
      stroke, and maternal death (&gt;76,000 maternal death annually).&#xD;
&#xD;
      The traditional approach to screening for preeclampsia endorsed by national guidelines is&#xD;
      based on a combination of maternal characteristics along with medical, obstetric and family&#xD;
      history.&#xD;
&#xD;
      However, although these methods are simple and easy to perform, maternal factors can only&#xD;
      identify less than 35% of all preeclampsia and approximately 40% of preterm-preeclampsia at a&#xD;
      false- positive rate of 10%.&#xD;
&#xD;
      More recently, multivariate analysis has been used to develop predictive models for&#xD;
      preeclampsia that can be applied as early as 11-13+6 weeks gestation. One such algorithm,&#xD;
      developed by the Fetal Medicine Foundation UK(MFM UK), incorporates maternal risk factors,&#xD;
      uterine artery doppler, mean arterial pressure, and serum markers of placental function and&#xD;
      placental growth factor. The FMFUK algorithm has been shown to predict approximately 75-90%&#xD;
      of those women destined to develop preeclampsia prior to 37 and 34 weeks respectively, at a&#xD;
      false positive rate of 10%. This algorithm has been validated prospectively in several&#xD;
      studies, including the prediction of other placental mediated complications of pregnancy,&#xD;
      such as fetal growth restriction and perinatal death.&#xD;
&#xD;
      The new clinical model will include the following additions to the existing first trimester&#xD;
      screening for aneuploidy:&#xD;
&#xD;
        -  Additional Clinical History&#xD;
&#xD;
        -  Blood pressure measurements&#xD;
&#xD;
        -  Ultrasound for uterine artery Doppler measurements&#xD;
&#xD;
        -  Expanded prenatal screening requisition&#xD;
&#xD;
        -  Quality assurance training of ultrasound technicians for the uterine artery doppler&#xD;
           measurements&#xD;
&#xD;
        -  Fetal Medicine Foundation validated risk calculation algorithm&#xD;
&#xD;
        -  Communicate results of the risk calculation algorithm from NYGH to SHSC and participant&#xD;
           health care providers.&#xD;
&#xD;
      While the ultimate goal will be to scale up and adapt this new clinical model, this protocol&#xD;
      focuses on the feasibility of implementing the new clinical model at a single centre,&#xD;
      Sunnybrook Health Sciences Centre.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">March 1, 2021</start_date>
  <completion_date type="Anticipated">June 1, 2022</completion_date>
  <primary_completion_date type="Anticipated">June 1, 2022</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Feasibility of Screening Tool</measure>
    <time_frame>11.3-13.6 weeks gestation</time_frame>
    <description>Implementation of the screening: To assess the feasibility, the investigators will judge success if the full screening process without deviation is completed for at least 90% of consented participants.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Accuracy of Screening</measure>
    <time_frame>11.3-13.6 weeks gestation</time_frame>
    <description>Reproducibility of the FMFUK studies. Planning a recruitment of 1000 participants and anticipating a 10% positive rate, the invetigators expect to follow 100 screen positive and 900 screen negative pregnancies.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Acceptability of Screening Tool to Participants</measure>
    <time_frame>11.3-13.6 weeks gestation</time_frame>
    <description>Proportion of acceptance/offer to implementation study. The investigators expect to obtain consent from 80% of pregnant women eligible for the study.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Compliance with low dose ASA for screen positive participants.</measure>
    <time_frame>16-36 weeks gestation</time_frame>
    <description>The investigators will assess the rate of initiation and maintenance of low dose ASA ( SHSC standard of care) as measured by phone follow-up at 16,22,26,32 and 36 weeks gestation, (2) follow-up at placental scan visit and (3) follow-up at delivery. Success will defined as 80% compliance.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Duration of the assessment</measure>
    <time_frame>11.3-13.6 weeks gestation</time_frame>
    <description>The investigators will assess the duration (in minute) required for completing data questionnaire, measuring arterial blood pressure and uterine artery Doppler</description>
  </other_outcome>
  <other_outcome>
    <measure>Turnaround time from assessment to results</measure>
    <time_frame>11.3-16 weeks gestation</time_frame>
    <description>The investigators will measure the turnaround time (in business day) from screening requisition reaching laboratory to report issued to SHSC via fax</description>
  </other_outcome>
  <other_outcome>
    <measure>Participant Satisfaction</measure>
    <time_frame>11.3-40 weeks gestation</time_frame>
    <description>The investigators will assess participant satisfaction with screening and care through a satisfaction survey with a 10 score scale where 1 is very unsatisfied and 10 is very satified</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">1000</enrollment>
  <condition>Pre-Eclampsia</condition>
  <arm_group>
    <arm_group_label>PE Enhanced Screening</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The PE screening program entails the following for all participants:&#xD;
provision of additional demographic and risk factors&#xD;
provision of mean arterial pressure&#xD;
standard nuchal translucency scan as part of their first trimester screening (FTS) with the addition of the measurement of the uterine artery Doppler by a certified sonographer&#xD;
standard blood sample (as part of the FTS)&#xD;
results of the PE screening (in the format of a screening report) will be provided to the study team and participant's healthcare provider</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Enhanced PE Screening</intervention_name>
    <description>To better identify women at risk for pre-eclampsia during pregnancy.</description>
    <arm_group_label>PE Enhanced Screening</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Women with a singleton pregnancy &gt; 18 years old&#xD;
&#xD;
          2. Not on low dose aspirin&#xD;
&#xD;
          3. Carrying a live fetus with crown rump length (CRL) between 41 and 84mm&#xD;
&#xD;
          4. Able to provide informed consent&#xD;
&#xD;
          5. Having a nuchal translucency ultrasound&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Women with a singleton pregnancy &lt; 18 years old&#xD;
&#xD;
          2. Women currently taking low dose aspirin&#xD;
&#xD;
          3. Women declining a nuchal translucency ultrasound&#xD;
&#xD;
          4. Women unable to provide informed consent&#xD;
&#xD;
          5. Women with a multiple pregnancy&#xD;
&#xD;
          6. Women with a demised fetus or a CRL &lt;41mm and &gt;84mm&#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>Ronzoni</last_name>
    <role>Principal Investigator</role>
    <affiliation>Sunnybrook Health Sciences Center</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Ronzoni</last_name>
    <phone>4164804920</phone>
    <email>stefania.ronzoni@sunnybrook.ca</email>
  </overall_contact>
  <location>
    <facility>
      <name>Sunnybrook Health Sciences center</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M4N 3M5</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Stefania Ronzoni</last_name>
      <email>stefania.ronzoni@sunnybrook.ca</email>
    </contact>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <reference>
    <citation>Wright D, Syngelaki A, Akolekar R, Poon LC, Nicolaides KH. Competing risks model in screening for preeclampsia by maternal characteristics and medical history. Am J Obstet Gynecol. 2015 Jul;213(1):62.e1-62.e10. doi: 10.1016/j.ajog.2015.02.018. Epub 2015 Feb 25.</citation>
    <PMID>25724400</PMID>
  </reference>
  <reference>
    <citation>O'Gorman N, Wright D, Poon LC, Rolnik DL, Syngelaki A, de Alvarado M, Carbone IF, Dutemeyer V, Fiolna M, Frick A, Karagiotis N, Mastrodima S, de Paco Matallana C, Papaioannou G, Pazos A, Plasencia W, Nicolaides KH. Multicenter screening for pre-eclampsia by maternal factors and biomarkers at 11-13 weeks' gestation: comparison with NICE guidelines and ACOG recommendations. Ultrasound Obstet Gynecol. 2017 Jun;49(6):756-760. doi: 10.1002/uog.17455. Erratum In: Ultrasound Obstet Gynecol. 2017 Dec;50(6):807.</citation>
    <PMID>28295782</PMID>
  </reference>
  <reference>
    <citation>Park FJ, Leung CH, Poon LC, Williams PF, Rothwell SJ, Hyett JA. Clinical evaluation of a first trimester algorithm predicting the risk of hypertensive disease of pregnancy. Aust N Z J Obstet Gynaecol. 2013 Dec;53(6):532-9. doi: 10.1111/ajo.12126. Epub 2013 Aug 6.</citation>
    <PMID>23919594</PMID>
  </reference>
  <reference>
    <citation>Mosimann B, Pfiffner C, Amylidi-Mohr S, Risch L, Surbek D, Raio L. First trimester combined screening for preeclampsia and small for gestational age - a single centre experience and validation of the FMF screening algorithm. Swiss Med Wkly. 2017 Aug 25;147:w14498. doi: 10.4414/smw.2017.14498. eCollection 2017.</citation>
    <PMID>28871576</PMID>
  </reference>
  <reference>
    <citation>O'Gorman N, Wright D, Poon LC, Rolnik DL, Syngelaki A, Wright A, Akolekar R, Cicero S, Janga D, Jani J, Molina FS, de Paco Matallana C, Papantoniou N, Persico N, Plasencia W, Singh M, Nicolaides KH. Accuracy of competing-risks model in screening for pre-eclampsia by maternal factors and biomarkers at 11-13 weeks' gestation. Ultrasound Obstet Gynecol. 2017 Jun;49(6):751-755. doi: 10.1002/uog.17399. Epub 2017 May 14. Erratum In: Ultrasound Obstet Gynecol. 2017 Dec;50(6):807.</citation>
    <PMID>28067011</PMID>
  </reference>
  <reference>
    <citation>Ananth CV, Keyes KM, Wapner RJ. Pre-eclampsia rates in the United States, 1980-2010: age-period-cohort analysis. BMJ. 2013 Nov 7;347:f6564. doi: 10.1136/bmj.f6564.</citation>
    <PMID>24201165</PMID>
  </reference>
  <verification_date>March 2021</verification_date>
  <study_first_submitted>April 16, 2020</study_first_submitted>
  <study_first_submitted_qc>June 1, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 2, 2020</study_first_posted>
  <last_update_submitted>March 17, 2021</last_update_submitted>
  <last_update_submitted_qc>March 17, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">March 22, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Eclampsia</mesh_term>
    <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/NCT04412681
org study id: PEprotocol
nct id: NCT04412681
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This study aims to evaluate the feasibility of implementing a clinical model for precision
      screening of early pre-eclampsia into the current prenatal screening service at Sunnybrook
      Health Sciences Center (SHSC).
Pre-eclampsia (PE) represents a pregnancy-specific systemic disorder that affects 3-8% of all
      pregnancies. In developed countries PE is considered a major public health problem
      responsible for severe maternal complications such as coagulopathy, renal and liver failure,
      stroke, and maternal death (>76,000 maternal death annually).

      The traditional approach to screening for preeclampsia endorsed by national guidelines is
      based on a combination of maternal characteristics along with medical, obstetric and family
      history.

      However, although these methods are simple and easy to perform, maternal factors can only
      identify less than 35% of all preeclampsia and approximately 40% of preterm-preeclampsia at a
      false- positive rate of 10%.

      More recently, multivariate analysis has been used to develop predictive models for
      preeclampsia that can be applied as early as 11-13+6 weeks gestation. One such algorithm,
      developed by the Fetal Medicine Foundation UK(MFM UK), incorporates maternal risk factors,
      uterine artery doppler, mean arterial pressure, and serum markers of placental function and
      placental growth factor. The FMFUK algorithm has been shown to predict approximately 75-90%
      of those women destined to develop preeclampsia prior to 37 and 34 weeks respectively, at a
      false positive rate of 10%. This algorithm has been validated prospectively in several
      studies, including the prediction of other placental mediated complications of pregnancy,
      such as fetal growth restriction and perinatal death.

      The new clinical model will include the following additions to the existing first trimester
      screening for aneuploidy:

        -  Additional Clinical History

        -  Blood pressure measurements

        -  Ultrasound for uterine artery Doppler measurements

        -  Expanded prenatal screening requisition

        -  Quality assurance training of ultrasound technicians for the uterine artery doppler
           measurements

        -  Fetal Medicine Foundation validated risk calculation algorithm

        -  Communicate results of the risk calculation algorithm from NYGH to SHSC and participant
           health care providers.

      While the ultimate goal will be to scale up and adapt this new clinical model, this protocol
      focuses on the feasibility of implementing the new clinical model at a single centre,
      Sunnybrook Health Sciences Centre.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: Feasibility of Screening Tool
time frame: 11.3-13.6 weeks gestation
description: Implementation of the screening: To assess the feasibility, the investigators will judge success if the full screening process without deviation is completed for at least 90% of consented participants.
measure: Accuracy of Screening
time frame: 11.3-13.6 weeks gestation
description: Reproducibility of the FMFUK studies. Planning a recruitment of 1000 participants and anticipating a 10% positive rate, the invetigators expect to follow 100 screen positive and 900 screen negative pregnancies.
measure: Acceptability of Screening Tool to Participants
time frame: 11.3-13.6 weeks gestation
description: Proportion of acceptance/offer to implementation study. The investigators expect to obtain consent from 80% of pregnant women eligible for the study.
measure: Compliance with low dose ASA for screen positive participants.
time frame: 16-36 weeks gestation
description: The investigators will assess the rate of initiation and maintenance of low dose ASA ( SHSC standard of care) as measured by phone follow-up at 16,22,26,32 and 36 weeks gestation, (2) follow-up at placental scan visit and (3) follow-up at delivery. Success will defined as 80% compliance.
measure: Duration of the assessment
time frame: 11.3-13.6 weeks gestation
description: The investigators will assess the duration (in minute) required for completing data questionnaire, measuring arterial blood pressure and uterine artery Doppler
measure: Turnaround time from assessment to results
time frame: 11.3-16 weeks gestation
description: The investigators will measure the turnaround time (in business day) from screening requisition reaching laboratory to report issued to SHSC via fax
measure: Participant Satisfaction
time frame: 11.3-40 weeks gestation
description: The investigators will assess participant satisfaction with screening and care through a satisfaction survey with a 10 score scale where 1 is very unsatisfied and 10 is very satified
arm group label: PE Enhanced Screening
arm group type: Experimental
description: The PE screening program entails the following for all participants:
provision of additional demographic and risk factors
provision of mean arterial pressure
standard nuchal translucency scan as part of their first trimester screening (FTS) with the addition of the measurement of the uterine artery Doppler by a certified sonographer
standard blood sample (as part of the FTS)
results of the PE screening (in the format of a screening report) will be provided to the study team and participant's healthcare provider
intervention type: Diagnostic Test
intervention name: Enhanced PE Screening
description: To better identify women at risk for pre-eclampsia during pregnancy.
arm group label: PE Enhanced Screening
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Ronzoni
role: Principal Investigator
affiliation: Sunnybrook Health Sciences Center
last name: Ronzoni
phone: 4164804920
email: stefania.ronzoni@sunnybrook.ca
facility: 
status: Recruiting
contact: 
country: Canada
citation: Wright D, Syngelaki A, Akolekar R, Poon LC, Nicolaides KH. Competing risks model in screening for preeclampsia by maternal characteristics and medical history. Am J Obstet Gynecol. 2015 Jul;213(1):62.e1-62.e10. doi: 10.1016/j.ajog.2015.02.018. Epub 2015 Feb 25.
PMID: 25724400
citation: O'Gorman N, Wright D, Poon LC, Rolnik DL, Syngelaki A, de Alvarado M, Carbone IF, Dutemeyer V, Fiolna M, Frick A, Karagiotis N, Mastrodima S, de Paco Matallana C, Papaioannou G, Pazos A, Plasencia W, Nicolaides KH. Multicenter screening for pre-eclampsia by maternal factors and biomarkers at 11-13 weeks' gestation: comparison with NICE guidelines and ACOG recommendations. Ultrasound Obstet Gynecol. 2017 Jun;49(6):756-760. doi: 10.1002/uog.17455. Erratum In: Ultrasound Obstet Gynecol. 2017 Dec;50(6):807.
PMID: 28295782
citation: Park FJ, Leung CH, Poon LC, Williams PF, Rothwell SJ, Hyett JA. Clinical evaluation of a first trimester algorithm predicting the risk of hypertensive disease of pregnancy. Aust N Z J Obstet Gynaecol. 2013 Dec;53(6):532-9. doi: 10.1111/ajo.12126. Epub 2013 Aug 6.
PMID: 23919594
citation: Mosimann B, Pfiffner C, Amylidi-Mohr S, Risch L, Surbek D, Raio L. First trimester combined screening for preeclampsia and small for gestational age - a single centre experience and validation of the FMF screening algorithm. Swiss Med Wkly. 2017 Aug 25;147:w14498. doi: 10.4414/smw.2017.14498. eCollection 2017.
PMID: 28871576
citation: O'Gorman N, Wright D, Poon LC, Rolnik DL, Syngelaki A, Wright A, Akolekar R, Cicero S, Janga D, Jani J, Molina FS, de Paco Matallana C, Papantoniou N, Persico N, Plasencia W, Singh M, Nicolaides KH. Accuracy of competing-risks model in screening for pre-eclampsia by maternal factors and biomarkers at 11-13 weeks' gestation. Ultrasound Obstet Gynecol. 2017 Jun;49(6):751-755. doi: 10.1002/uog.17399. Epub 2017 May 14. Erratum In: Ultrasound Obstet Gynecol. 2017 Dec;50(6):807.
PMID: 28067011
citation: Ananth CV, Keyes KM, Wapner RJ. Pre-eclampsia rates in the United States, 1980-2010: age-period-cohort analysis. BMJ. 2013 Nov 7;347:f6564. doi: 10.1136/bmj.f6564.
PMID: 24201165
responsible party type: Sponsor
mesh term: Eclampsia
mesh term: Pre-Eclampsia