<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/NCT03814096</url>
  </required_header>
  <id_info>
    <org_study_id>49086</org_study_id>
    <nct_id>NCT03814096</nct_id>
  </id_info>
  <brief_title>Point-Of-Care Testing for Congenital Syphilis in Mothers and Newborns</brief_title>
  <official_title>Point-Of-Care Testing for Congenital Syphilis in Mothers and Newborns: A Proof of Concept Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Stanford University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Santa Clara Valley Medical Center</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Stanford University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      A dramatic rise in syphilis has been recently reported in the US between 2000-2017, which was&#xD;
      followed also by a dramatic rise in congenital syphilis (CS). In 2017 there were 918 CS cases&#xD;
      reported in the United States, including 64 syphilitic stillbirths. In 2017, California (CA)&#xD;
      had one of the highest syphilis rates among women and this was accompanied by a dramatic&#xD;
      increase in CS cases. Approximately 40% of CS cases in the United States occurred from&#xD;
      maternal infections acquired late in gestation, missed by current-early gestation&#xD;
      only-prenatal screening. More frequent prenatal screening late in gestation is urgently&#xD;
      needed. However, cost considerations and operational logistic limitations preclude&#xD;
      implementation even in high risk regions. There is an urgent need for widespread&#xD;
      implementation of more frequent prenatal screening using alternative cost-saving screening&#xD;
      approaches. The Syphilis-Health-Check (SHC) point-of-care (POC) test is a well validated&#xD;
      POC-test that is already commercially available in the US, is approved by the Federal Drug&#xD;
      Administration (FDA) and Clinical Laboratory Improvement Amendments (CLIA)-waived. POC&#xD;
      prenatal syphilis screening late in gestation using a well validated POC-test (in addition to&#xD;
      the standard early gestation-screening with laboratory-based tests) could provide a&#xD;
      cost-saving complementary alternative that could benefit patients, mitigate the higher cost&#xD;
      associated with more frequent testing, overcome operational limitations and contribute to the&#xD;
      elimination of CS. Moreover, POC-neonatal and placental screening could provide an additional&#xD;
      complementary safeguard approach to decrease missed/delayed CS diagnoses.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Given the dramatic rise in syphilis that has been recently reported in the United States in&#xD;
      the recent years (between 2000-2017) there is an urgent need for widespread implementation of&#xD;
      more frequent prenatal syphilis screening using alternative cost-saving screening approaches.&#xD;
      The Syphilis-Health-Check (SHC) point-of-care (POC) test is a well validated POC-test that is&#xD;
      already commercially available in the United States, is approved by the Federal Drug&#xD;
      Administration (FDA) and Clinical Laboratory Improvement Amendments (CLIA)-waived.&#xD;
      Hypotheses: a) Point-Of-Care (POC) prenatal syphilis screening late in gestation using a well&#xD;
      validated POC-test (in addition to the standard early gestation-screening with lab-based&#xD;
      tests) could provide a cost-saving complementary alternative that could benefit patients,&#xD;
      mitigate the higher cost associated with the need for more frequent syphilis screening,&#xD;
      overcome operational limitations and contribute to the elimination of CS. b) POC-neonatal&#xD;
      screening can provide additional complementary safeguard approach to decrease missed/delayed&#xD;
      CS diagnoses. POC-neonatal syphilis screening can be used as a rapid screening tool to&#xD;
      capture/probe all neonatal cases who would need immediate medical attention and further&#xD;
      investigation and workup to rule out (or rule-in accordingly) suspected/probable CS.&#xD;
&#xD;
      Specific Aim 1: Validate the diagnostic accuracy of SHC-POC-test in late gestation (24-28&#xD;
      weeks): a) against standard laboratory based syphilis treponemal tests (TT)/and&#xD;
      non-treponemal tests (NTT) in prenatal-care clinic settings and b) also against clinical&#xD;
      diagnoses of maternal syphilis requiring treatment during gestation (co-primary endpoint).&#xD;
      Specific aim 2: Test the feasibility of POC-prenatal screening (secondary endpoint) and&#xD;
      efficacy of POC-prenatal screening to decrease the incidence of CS in a high risk region,&#xD;
      through prompt diagnosis (and treatment accordingly) of maternal syphilis cases that need&#xD;
      immediate treatment (to prevent mother-to -child transmission) (co-primary endpoint).&#xD;
      Specific Aim 3: Evaluate the feasibility of POC-neonatal screening and POC-placental&#xD;
      screening and the concordance of the results between late gestation maternal, neonatal and&#xD;
      placental POC-test results. (Proof of concept; secondary endpoints).&#xD;
&#xD;
      Study design: (a) Prospective cohort study in the Santa Clara Valley Medical Center (SCVMC),&#xD;
      San Jose, CA over a 3 yr study period with enrollment of pregnant women at 24-28 weeks (wks)&#xD;
      gestational age (GA), presenting for their routine clinic visit at 24-28 wks for their&#xD;
      glucose tolerance test (GTT). SCVMC recently introduced as a new standard of care rescreening&#xD;
      for syphilis of all pregnant women at 24-28 wks with TT/NTTs, bundled to the venipuncture for&#xD;
      the Glucose Tolerance Test (GTT). During this clinic visit, the syphilis POC-testing will be&#xD;
      done via a fingerstick in clinic, while the standard lab-based syphilis screening will be&#xD;
      done via venipuncture in the lab (as part of the new standard of care). (b) Proof-of-concept&#xD;
      prospective cohort substudy to test the feasibility of neonatal POC-testing (whole-blood&#xD;
      collected via heel stick, bundled with the routine newborn screening for inborn errors of&#xD;
      metabolism at 24-48 hours of life) and placental-POC-testing.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    funding not secured&#xD;
  </why_stopped>
  <start_date type="Anticipated">October 30, 2019</start_date>
  <completion_date type="Anticipated">October 29, 2023</completion_date>
  <primary_completion_date type="Anticipated">October 29, 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>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Count of pregnant women with concordant test results between the SHC-POC test and the TT/NTT test at 24-28 weeks gestational age, as a measure of validation of the diagnostic accuracy of the SHC-POC-test</measure>
    <time_frame>Between 24-28 weeks gestational age of study participants</time_frame>
    <description>Diagnostic accuracy of SHC-POC test against standard laboratory diagnostic tests for syphilis (TT/NTT) in late gestation (24-28 weeks)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Count of pregnant women with concordant test results between the SHC-POC test and maternal syphilis diagnosis at 24-28 weeks gestational age requiring treatment during gestation, as a measure of validation of the diagnostic accuracy of the SHC-POC test</measure>
    <time_frame>Between 24-28 weeks gestational age of study participants</time_frame>
    <description>Diagnostic accuracy of SHC-POC test against maternal syphilis diagnosis late in gestation requiring treatment during gestation (24-28 weeks)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of Congenital Syphilis (N of congenital Syphilis cases/ N of total births), as a measure of efficacy of POC-prenatal syphilis screening at 24-28 weeks gestational age</measure>
    <time_frame>At birth and up to 3 months of age of offsprings of study participants</time_frame>
    <description>The efficacy of SHC-POC prenatal screening in decreasing the incidence of Congenital Syphilis will be calculated. Comparison will be made between the incidence rate of Congenital Syphilis cases before the SHC-POC-prenatal screening (among all births in Santa Clara Valley Medical Center, San Jose, CA in the year before the SHC-POC-prenatal screening) and 3 years after the implementation of the SHC POC-prenatal screening (among all births from the screened participating pregnant women)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Count of concordant SHC-POC-test results between maternal, placental and neonatal SHC-POC-testing.</measure>
    <time_frame>At 24-28 weeks gestational age of study participants (for maternal POC-test results); During Delivery (for placental POC-test results) and at birth and up to 3 months of age of offsprings of study participants (for neonatal POC-test results)</time_frame>
    <description>As a proof of concept, testing with the SHC-POC test also the placenta (at the time of delivery) and the offsprings of a minimum 20 consenting pregnant women will be done. The counts of SHC-POC test results that were concordant in the mothers, placentas and newborns will be calculated.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Maternal Syphilis During Pregnancy - Baby Not Yet Delivered</condition>
  <condition>Congenital Syphilis</condition>
  <arm_group>
    <arm_group_label>Syphilis POC-prenatal screening</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Syphilis prenatal screening late in gestation at 24-28 weeks (at the time of the routine prenatal care clinic visit for the routine Glucose Tolerance Test [GTT]) using the Syphilis Health Check POC-test (Diagnostics Direct LLC, NJ)</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Syphilis Health Check POC-test (Diagnostics Direct LLC, NJ)</intervention_name>
    <description>Syphilis Health Check (SHC) POC-test is a treponemal POC-test based on 3d generation enzyme immunoassay (EIA) method detecting both Immunoglobulin G (IgG) and Immunoglobulin M (IgM) antibodies.</description>
    <arm_group_label>Syphilis POC-prenatal screening</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Consenting adult pregnant women between 24-28 weeks GA seen at Obstetrics/Gynecology&#xD;
             (OB/GYN) prenatal-care clinics in Santa Clara Valley Medical Center San Jose CA, at&#xD;
             the time of their routine clinic visit at 24-28 weeks GA for their routine&#xD;
             glucose-tolerance-test (GTT) prenatal screening.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Non-adult pregnant patients &lt;18 years of age and pregnant women not between 24-28&#xD;
             weeks gestational age at the time of the clinic visit.&#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>Despina G. Contopoulos-Ioannidis, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Stanford University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Santa Clara Valley Medical Center; Department of Obstetrics &amp; Gynecology and Pediatrics</name>
      <address>
        <city>San Jose</city>
        <state>California</state>
        <zip>95128</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Stanford University School of Medicine, Department of Pediatrics, Division of Infectious Diseases</name>
      <address>
        <city>Stanford</city>
        <state>California</state>
        <zip>94305</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>December 2019</verification_date>
  <study_first_submitted>January 18, 2019</study_first_submitted>
  <study_first_submitted_qc>January 22, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 23, 2019</study_first_posted>
  <last_update_submitted>December 11, 2019</last_update_submitted>
  <last_update_submitted_qc>December 11, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">December 13, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Stanford University</investigator_affiliation>
    <investigator_full_name>Despina Contopoulos-Ioannidis</investigator_full_name>
    <investigator_title>Clinical Associate Professor, Department of Pediatrics, Division of Infectious Diseases, Stanford University School of Medicine</investigator_title>
  </responsible_party>
  <keyword>Syphilis, prenatal screening, SHC, point-of-care test</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Syphilis</mesh_term>
    <mesh_term>Syphilis, Congenital</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>We plan to share the study protocol and the study analysis plan. The informed consent forms and the database with the completely de-identified patient data (without any Personal Health Information (PHI)) will become available upon request from the study Principal Investigator.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_time_frame>The data will become available within 2 years from the completion of the study and will stay available.</ipd_time_frame>
    <ipd_access_criteria>The informed consent forms and the database with the completely de-identified patient data (without any Personal Health Information (PHI)) will become available upon request from the study Principal Investigator.</ipd_access_criteria>
  </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/NCT03814096
org study id: 49086
nct id: NCT03814096
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: Yes
is us export: No
A dramatic rise in syphilis has been recently reported in the US between 2000-2017, which was
      followed also by a dramatic rise in congenital syphilis (CS). In 2017 there were 918 CS cases
      reported in the United States, including 64 syphilitic stillbirths. In 2017, California (CA)
      had one of the highest syphilis rates among women and this was accompanied by a dramatic
      increase in CS cases. Approximately 40% of CS cases in the United States occurred from
      maternal infections acquired late in gestation, missed by current-early gestation
      only-prenatal screening. More frequent prenatal screening late in gestation is urgently
      needed. However, cost considerations and operational logistic limitations preclude
      implementation even in high risk regions. There is an urgent need for widespread
      implementation of more frequent prenatal screening using alternative cost-saving screening
      approaches. The Syphilis-Health-Check (SHC) point-of-care (POC) test is a well validated
      POC-test that is already commercially available in the US, is approved by the Federal Drug
      Administration (FDA) and Clinical Laboratory Improvement Amendments (CLIA)-waived. POC
      prenatal syphilis screening late in gestation using a well validated POC-test (in addition to
      the standard early gestation-screening with laboratory-based tests) could provide a
      cost-saving complementary alternative that could benefit patients, mitigate the higher cost
      associated with more frequent testing, overcome operational limitations and contribute to the
      elimination of CS. Moreover, POC-neonatal and placental screening could provide an additional
      complementary safeguard approach to decrease missed/delayed CS diagnoses.
Given the dramatic rise in syphilis that has been recently reported in the United States in
      the recent years (between 2000-2017) there is an urgent need for widespread implementation of
      more frequent prenatal syphilis screening using alternative cost-saving screening approaches.
      The Syphilis-Health-Check (SHC) point-of-care (POC) test is a well validated POC-test that is
      already commercially available in the United States, is approved by the Federal Drug
      Administration (FDA) and Clinical Laboratory Improvement Amendments (CLIA)-waived.
      Hypotheses: a) Point-Of-Care (POC) prenatal syphilis screening late in gestation using a well
      validated POC-test (in addition to the standard early gestation-screening with lab-based
      tests) could provide a cost-saving complementary alternative that could benefit patients,
      mitigate the higher cost associated with the need for more frequent syphilis screening,
      overcome operational limitations and contribute to the elimination of CS. b) POC-neonatal
      screening can provide additional complementary safeguard approach to decrease missed/delayed
      CS diagnoses. POC-neonatal syphilis screening can be used as a rapid screening tool to
      capture/probe all neonatal cases who would need immediate medical attention and further
      investigation and workup to rule out (or rule-in accordingly) suspected/probable CS.

      Specific Aim 1: Validate the diagnostic accuracy of SHC-POC-test in late gestation (24-28
      weeks): a) against standard laboratory based syphilis treponemal tests (TT)/and
      non-treponemal tests (NTT) in prenatal-care clinic settings and b) also against clinical
      diagnoses of maternal syphilis requiring treatment during gestation (co-primary endpoint).
      Specific aim 2: Test the feasibility of POC-prenatal screening (secondary endpoint) and
      efficacy of POC-prenatal screening to decrease the incidence of CS in a high risk region,
      through prompt diagnosis (and treatment accordingly) of maternal syphilis cases that need
      immediate treatment (to prevent mother-to -child transmission) (co-primary endpoint).
      Specific Aim 3: Evaluate the feasibility of POC-neonatal screening and POC-placental
      screening and the concordance of the results between late gestation maternal, neonatal and
      placental POC-test results. (Proof of concept; secondary endpoints).

      Study design: (a) Prospective cohort study in the Santa Clara Valley Medical Center (SCVMC),
      San Jose, CA over a 3 yr study period with enrollment of pregnant women at 24-28 weeks (wks)
      gestational age (GA), presenting for their routine clinic visit at 24-28 wks for their
      glucose tolerance test (GTT). SCVMC recently introduced as a new standard of care rescreening
      for syphilis of all pregnant women at 24-28 wks with TT/NTTs, bundled to the venipuncture for
      the Glucose Tolerance Test (GTT). During this clinic visit, the syphilis POC-testing will be
      done via a fingerstick in clinic, while the standard lab-based syphilis screening will be
      done via venipuncture in the lab (as part of the new standard of care). (b) Proof-of-concept
      prospective cohort substudy to test the feasibility of neonatal POC-testing (whole-blood
      collected via heel stick, bundled with the routine newborn screening for inborn errors of
      metabolism at 24-48 hours of life) and placental-POC-testing.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: Count of pregnant women with concordant test results between the SHC-POC test and the TT/NTT test at 24-28 weeks gestational age, as a measure of validation of the diagnostic accuracy of the SHC-POC-test
time frame: Between 24-28 weeks gestational age of study participants
description: Diagnostic accuracy of SHC-POC test against standard laboratory diagnostic tests for syphilis (TT/NTT) in late gestation (24-28 weeks)
measure: Count of pregnant women with concordant test results between the SHC-POC test and maternal syphilis diagnosis at 24-28 weeks gestational age requiring treatment during gestation, as a measure of validation of the diagnostic accuracy of the SHC-POC test
time frame: Between 24-28 weeks gestational age of study participants
description: Diagnostic accuracy of SHC-POC test against maternal syphilis diagnosis late in gestation requiring treatment during gestation (24-28 weeks)
measure: Incidence of Congenital Syphilis (N of congenital Syphilis cases/ N of total births), as a measure of efficacy of POC-prenatal syphilis screening at 24-28 weeks gestational age
time frame: At birth and up to 3 months of age of offsprings of study participants
description: The efficacy of SHC-POC prenatal screening in decreasing the incidence of Congenital Syphilis will be calculated. Comparison will be made between the incidence rate of Congenital Syphilis cases before the SHC-POC-prenatal screening (among all births in Santa Clara Valley Medical Center, San Jose, CA in the year before the SHC-POC-prenatal screening) and 3 years after the implementation of the SHC POC-prenatal screening (among all births from the screened participating pregnant women)
measure: Count of concordant SHC-POC-test results between maternal, placental and neonatal SHC-POC-testing.
time frame: At 24-28 weeks gestational age of study participants (for maternal POC-test results); During Delivery (for placental POC-test results) and at birth and up to 3 months of age of offsprings of study participants (for neonatal POC-test results)
description: As a proof of concept, testing with the SHC-POC test also the placenta (at the time of delivery) and the offsprings of a minimum 20 consenting pregnant women will be done. The counts of SHC-POC test results that were concordant in the mothers, placentas and newborns will be calculated.
arm group label: Syphilis POC-prenatal screening
arm group type: Experimental
description: Syphilis prenatal screening late in gestation at 24-28 weeks (at the time of the routine prenatal care clinic visit for the routine Glucose Tolerance Test [GTT]) using the Syphilis Health Check POC-test (Diagnostics Direct LLC, NJ)
intervention type: Diagnostic Test
intervention name: Syphilis Health Check POC-test (Diagnostics Direct LLC, NJ)
description: Syphilis Health Check (SHC) POC-test is a treponemal POC-test based on 3d generation enzyme immunoassay (EIA) method detecting both Immunoglobulin G (IgG) and Immunoglobulin M (IgM) antibodies.
arm group label: Syphilis POC-prenatal screening
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Despina G. Contopoulos-Ioannidis, MD
role: Principal Investigator
affiliation: Stanford University
facility: 
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Stanford University
investigator full name: Despina Contopoulos-Ioannidis
investigator title: Clinical Associate Professor, Department of Pediatrics, Division of Infectious Diseases, Stanford University School of Medicine
mesh term: Syphilis
mesh term: Syphilis, Congenital
sharing ipd: Yes
ipd description: We plan to share the study protocol and the study analysis plan. The informed consent forms and the database with the completely de-identified patient data (without any Personal Health Information (PHI)) will become available upon request from the study Principal Investigator.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Clinical Study Report (CSR)
ipd time frame: The data will become available within 2 years from the completion of the study and will stay available.
ipd access criteria: The informed consent forms and the database with the completely de-identified patient data (without any Personal Health Information (PHI)) will become available upon request from the study Principal Investigator.