<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/NCT04474223</url>
  </required_header>
  <id_info>
    <org_study_id>20-00363</org_study_id>
    <nct_id>NCT04474223</nct_id>
  </id_info>
  <brief_title>Surveillance and Treatment to Prevent Fetal Atrioventricular Block Likely to Occur Quickly (STOP BLOQ)</brief_title>
  <official_title>Surveillance and Treatment to Prevent Fetal Atrioventricular Block Likely to Occur Quickly (STOP BLOQ)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>NYU Langone Health</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>NYU Langone Health</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Fetal complete (i.e., third degree, 3°) atrioventricular block (AVB), identified in the 2nd&#xD;
      trimester of pregnancy in an otherwise normally developing heart, is almost universally&#xD;
      associated with maternal anti-Ro autoantibodies and results in death in a fifth of cases. To&#xD;
      date treatment of 3° AVB has been ineffective in restoring normal rhythm (NR) which may be&#xD;
      because current surveillance is limited to once- weekly fetal echocardiograms. It is&#xD;
      hypothesized that there may be a vital transition period of several hours in which incomplete&#xD;
      block (2° AVB) may be successfully treated avoiding fully advanced irreversible 3° AVB. To&#xD;
      optimize the likelihood of timely detection of the transition period this study comprises&#xD;
      three steps: 1) to risk stratify for high titer anti-Ro antibodies, which are necessary but&#xD;
      not sufficient to develop fetal AVB; 2) to empower mothers to identify 2° AVB by using fetal&#xD;
      heart rate and rhythm monitoring (FHRM) at home, and 3) to rapidly treat mothers who detect&#xD;
      an abnormality by monitoring with an urgent echocardiogram that confirms 2° AVB with the hope&#xD;
      of reversing 2° AVB before it becomes permanent (3° AVB). In addition, it will be determined&#xD;
      if FHRM reduces the need for weekly echoes. Although mothers with low titer anti-Ro will not&#xD;
      be continued in Step 2 and therefore not followed by FHRM, birth ECGs will be collected to&#xD;
      confirm that low titer antibodies do not confer risk. It is anticipated that this study will&#xD;
      provide an evidenced based surveillance strategy for those mothers at high risk of having a&#xD;
      child with 3° AVB.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Fetal complete (3°) atrioventricular block (AVB), identified in the 2nd trimester in an&#xD;
      otherwise normally developing heart, is almost universally associated with maternal anti-Ro&#xD;
      autoantibodies, which transcytose the placenta via the trophoblastic IgG receptor, FcγRn. The&#xD;
      burden of 3° AVB is considerable: perinatal mortality of 18% exceeds that for all non-cardiac&#xD;
      congenital anomalies combined, and almost all survivors require lifelong cardiac pacing with&#xD;
      its associated complications. It has been speculated that full expression of conduction&#xD;
      disease occurs by sequential fetal progression from normal rhythm (NR) to 1° AVB [prolonged&#xD;
      AV interval assessed by echocardiogram (echo)], to 2° AVB (irregular cardiac rhythm or&#xD;
      bradycardia), culminating in 3° AVB. Fetal heart rate and rhythm monitoring (FHRM) suggests a&#xD;
      time interval of ~12 hours for the transition from NR to 3° AVB, albeit the culprit biologic&#xD;
      processes (inflammation leading to fibrosis) likely initiate prior to clinical detection.&#xD;
      Anecdotal evidence suggests this transition period, marked by an irregular rhythm and/or&#xD;
      bradycardia, may be the only window of opportunity for anti-inflammatory treatment to restore&#xD;
      NR.&#xD;
&#xD;
      A barrier to preventing progression to 3° AVB is the absence of a technique to accurately&#xD;
      surveil for the precipitate transition from NR to 3° AVB. Surveillance limited to weekly&#xD;
      echos (current standard of care) may be too infrequent to detect this transition period when&#xD;
      treatment is most likely to be effective. We have now obviated this obstacle and shown that&#xD;
      ambulatory FHRM by the mother at home with confirmation of abnormal findings by echo is not&#xD;
      only feasible but may afford rapid treatment restoring NR. Combining results from studies&#xD;
      comprising 275 anti-Ro+ pregnancies, 87% completed monitoring with a false positive rate of&#xD;
      5%. In 4 cases of 2° AVB identified by FHRM and treated &lt;12h, AVB reversed. Remarkably, no&#xD;
      cases of 2° or 3° AVB were missed, suggesting mothers can recognize abnormal FHRM, reducing&#xD;
      or precluding the need for weekly echos.&#xD;
&#xD;
      The proposed project combines the expertise of fetal cardiologist Bettina F. Cuneo, MD,&#xD;
      initiator and PI of the FHRM program, and rheumatologist Jill P. Buyon, MD, founder/director&#xD;
      of the largest extant registry of anti-Ro-mediated AVB, whose research on the pathogenesis&#xD;
      supports a fetal inflammatory component associated with high-titer antibodies. Participants&#xD;
      will be referred from 35 sites in 3 sequential Steps: 1) Screening for high titer anti-Ro60&#xD;
      or Ro52 centrally in Dr. Buyon's lab; 2) Surveillance by FHRM 3x daily and weekly echo; 3)&#xD;
      Treatment of 2° AVB identified by FHRM confirmed by echo. Feasibility of FHRM supported by&#xD;
      weekly echo of high-autoantibody-titer mothers will be leveraged to address the efficacy of&#xD;
      expeditious (&lt;12 h after detection) treatment of 2° AVB as well as the incidence/outcome of&#xD;
      AV interval prolongation and extra-nodal disease.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">August 1, 2020</start_date>
  <completion_date type="Anticipated">October 31, 2026</completion_date>
  <primary_completion_date type="Anticipated">August 1, 2025</primary_completion_date>
  <phase>Phase 3</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>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percentage of 2° AVB subjects with NR (1:1 AV conduction) at birth</measure>
    <time_frame>up to 25 weeks post-enrollment</time_frame>
    <description>The presence of NR (normal rhythm) will be determined by electrocardiogram (ECG)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percentage of 2° AVB subjects who maintain NR at age 1 year.</measure>
    <time_frame>1 year post-birth</time_frame>
    <description>The presence of NR will be determined by ECG</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of AV interval &gt; 170 msec subjects with NR at birth</measure>
    <time_frame>At birth</time_frame>
    <description>AV intervals will be determined by EKG</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidences of isolated extra-nodal cardiac disease</measure>
    <time_frame>up to 1 year post-birth</time_frame>
    <description>Extra-nodal cardiac disease includes: Endocardial fibroelastosis, dilated cardiomyopathy, and AV valve insufficiency. Isolated exta-nodal cardiac disease will be determined by echocardiogram.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">1300</enrollment>
  <condition>AVB - Atrioventricular Block</condition>
  <condition>Fetal AVB</condition>
  <arm_group>
    <arm_group_label>Mothers with Fetuses Who Have 2° AVB or AV interval &gt; 170ms</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dexamethasone</intervention_name>
    <description>In mother in whom 2° AVB or AV interval &gt;170 ms has been diagnosed in the fetus:&#xD;
Dexamethasone 8 mg po/day for 10 days. Then dexamethasone 4 mg po/ day through 28 weeks 6 days gestational age (GA); then 3 mg/day from 29 wks 0 days to 29 wks 6 days GA; then 2 mg/day until delivery</description>
    <arm_group_label>Mothers with Fetuses Who Have 2° AVB or AV interval &gt; 170ms</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>IVIG</intervention_name>
    <description>In a mother in whom 2° AVB has been diagnosed in the fetus:&#xD;
One dose of IVIG [1g/kg of maternal weight (max dose 70 g)] at diagnosis of 2° AVB (within 12 hours of detection by mother via home monitoring and within 6 hours of confirmation by echocardiogram). A fetal AV interval &gt; 170 ms will not be treated with maternal IVIG, only dexamethasone.</description>
    <arm_group_label>Mothers with Fetuses Who Have 2° AVB or AV interval &gt; 170ms</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Provision of signed and dated informed consent form&#xD;
&#xD;
          2. Stated willingness to comply with all study procedures and availability for the&#xD;
             duration of the study&#xD;
&#xD;
          3. Be &lt;18 weeks pregnant at the time of enrollment&#xD;
&#xD;
          4. Titer of anti-Ro 52 or 60 antibodies ≥1,000 EU&#xD;
&#xD;
          5. Any positive titer of anti-Ro if a history of a previously affected child&#xD;
&#xD;
          6. Ability to take oral medication and be willing to adhere to the dexamethasone and IVIG&#xD;
             protocols.&#xD;
&#xD;
          7. Ability to perform Doppler fetal heart rate and rhythm monitoring in the ambulatory&#xD;
             setting,&#xD;
&#xD;
          8. Ability to send an audiotext message by cell phone therefore the participant will be&#xD;
             informed that they need a phone with texting capabilities. Located within 6 hours&#xD;
             drive of the participating pediatric cardiology site&#xD;
&#xD;
          9. Be ≥18 years of age&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Multi-fetal pregnancy&#xD;
&#xD;
          2. Known allergic reactions to components of IVIG, or dexamethasone or maternal IgA&#xD;
             deficiency&#xD;
&#xD;
          3. Fetal conduction system disease already present in the current pregnancy&#xD;
&#xD;
          4. Any women who in the opinion of the investigator cannot understand the consent form or&#xD;
             be able to perform thrice daily home monitoring or recognize an abnormal fetal heart&#xD;
             rate or rhythm&#xD;
&#xD;
          5. Women prisoners&#xD;
&#xD;
          6. Treatment with &gt;20 mg/prednisone q day or with any dose of fluorinated steroids at&#xD;
             enrollment&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <gender_based>Yes</gender_based>
    <gender_description>Must be &lt;18 weeks pregnant at the time of enrollment</gender_description>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jill Buyon, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>NYU Langone Health</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Bettina Cuneo, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Colorado, Denver</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Mala Masson</last_name>
    <phone>212-263-0372</phone>
    <email>mala.masson@nyulangone.org</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Jill Buyon, MD</last_name>
    <phone>212-263-0756</phone>
    <email>Jill.Buyon@nyulangone.org,</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Phoenix Children's Hospital/Dignity Health</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85016</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Christopher Lindblade, MD</last_name>
      <email>clindblade@phoenixchildrens.com</email>
    </contact>
    <investigator>
      <last_name>Christopher Lindblade, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>University of California - Los Angeles (UCLA)</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90095</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Gary Satou, MD</last_name>
      <email>GSatou@mednet.ucla.edu</email>
    </contact>
    <contact_backup>
      <last_name>Mark Sklansky, MD</last_name>
      <email>MSklansky@mednet.ucla.edu</email>
    </contact_backup>
    <investigator>
      <last_name>Gary Satou, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Mark Sklansky, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>D Krakow, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Stanford University</name>
      <address>
        <city>Palo Alto</city>
        <state>California</state>
        <zip>94305</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Theresa Tacy, MD</last_name>
      <email>tatacy@stanford.edu</email>
    </contact>
    <contact_backup>
      <last_name>Michelle Kaplinski, MD</last_name>
      <email>mkaplinsk@stanford.edu</email>
    </contact_backup>
    <investigator>
      <last_name>Theresa Tacy, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Michelle Kaplinski, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>University of California-San Francisco</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94143</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Anita Mood-Grady, MD</last_name>
      <email>Anita.Grady@ucsf.edu</email>
    </contact>
    <investigator>
      <last_name>Anita Mood-Grady, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>University of Colorado, Denver (UCD)</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80204</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Bettina Cuneo, MD</last_name>
      <phone>720-777-1030</phone>
      <email>Bettina.Cuneo@childrenscolorado.org</email>
    </contact>
    <investigator>
      <last_name>Bettina Cuneo, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Yale University School of Medicine</name>
      <address>
        <city>New Haven</city>
        <state>Connecticut</state>
        <zip>06510</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Joshua Copel, MD</last_name>
      <email>joshua.copel@yale.edu</email>
    </contact>
    <investigator>
      <last_name>Joshua Copel, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Children's National Medical Center/George Washington University</name>
      <address>
        <city>Washington</city>
        <state>District of Columbia</state>
        <zip>20010</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Anita Krishnan, MD</last_name>
      <email>AKrishna@childrensnational.org</email>
    </contact>
    <contact_backup>
      <last_name>Mary Donofrio, MD</last_name>
      <email>MDonofri@childrensnational.org</email>
    </contact_backup>
    <investigator>
      <last_name>Anita Krishnan, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Mary Donofrio, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>University of Kentucky / Kentucky Children's Hospital</name>
      <address>
        <city>Lexington</city>
        <state>Kentucky</state>
        <zip>40536</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Kristopher Cumbermack, MD</last_name>
      <email>KCumbermack@uky.edu</email>
    </contact>
    <investigator>
      <last_name>Kristopher Cumbermack, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>University of Louisville / Norton Children's Hospital</name>
      <address>
        <city>Louisville</city>
        <state>Kentucky</state>
        <zip>40202</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Jyothi Matta, MBBS</last_name>
      <email>Jyothi.Matta@louisville.edu</email>
    </contact>
    <contact_backup>
      <last_name>Brian Holland, MD</last_name>
      <email>brian.holland@louisville.edu</email>
    </contact_backup>
    <investigator>
      <last_name>Jyothi Matta, MBBS</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Brian Holland, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>University of Michigan / C. S. Mott Children's Hospital</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48109</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Sonal Owens, MD</last_name>
      <email>sthakkar@med.umich.edu</email>
    </contact>
    <investigator>
      <last_name>Sonal Owens, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Jimmy Lu, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Children's Hospital of Minnesota</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <zip>55404</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Lisa Howley, MD</last_name>
      <email>lhowley@chc-pa.org</email>
    </contact>
    <investigator>
      <last_name>Lisa Howley, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Perinatal Associates of New Mexico</name>
      <address>
        <city>Rio Rancho</city>
        <state>New Mexico</state>
        <zip>87124</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Gary Joffe, MD</last_name>
      <email>gjoffe@panm.com</email>
    </contact>
    <investigator>
      <last_name>Gary Joffe, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>NYU Langone Health</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10016</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Colin Phoon, MD</last_name>
      <email>Colin.Phoon@nyulangone.org</email>
    </contact>
    <investigator>
      <last_name>Jill Buyon, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Colin Phoon, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Mount Sinai</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10029</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Erin Paul, MD</last_name>
      <email>Erin.Paul@mssm.edu</email>
    </contact>
    <investigator>
      <last_name>Erin Paul, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Columbia University Medical Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10032</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Stephanie Levasseur, MD</last_name>
      <email>sl2363@cumc.columbia.edu</email>
    </contact>
    <investigator>
      <last_name>Stephanie Levasseur, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>UH Rainbow Babies / Children's Hospital</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44106</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>James Strainic, MD</last_name>
      <email>James.Strainic@UHhospitals.org</email>
    </contact>
    <investigator>
      <last_name>James Strainic, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Cleveland Clinic Lerner College of Medicine</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44195</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Rukmini Komarlu, MD</last_name>
      <email>komarlr@ccf.org</email>
    </contact>
    <investigator>
      <last_name>Rukmini Komarlu, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Vanderbilt University Medical Center</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37232</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Stacy Stratemann-Killen, MD</last_name>
      <email>stacy.stratemann@vumc.org</email>
    </contact>
    <investigator>
      <last_name>Stacy Stratemann-Killen, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </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>
    <status>Recruiting</status>
    <contact>
      <last_name>Tam Doan, MD</last_name>
      <email>tam.doan@bcm.edu</email>
    </contact>
    <investigator>
      <last_name>Tam Doan, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Shreya Sheth, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>University of Utah Health</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84102</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Whitnee Hogan, MD</last_name>
      <email>Whitnee.Hogan@hsc.utah.edu</email>
    </contact>
    <investigator>
      <last_name>Whitnee Hogan, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>University of Vermont Children's Hospital</name>
      <address>
        <city>Burlington</city>
        <state>Vermont</state>
        <zip>05401</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Caitlin Haxel, MD</last_name>
      <email>caitlin.haxel@uvmhealth.org</email>
    </contact>
    <investigator>
      <last_name>Caitlin Haxel, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Eastern Virginia Medical School (EVMS)</name>
      <address>
        <city>Norfolk</city>
        <state>Virginia</state>
        <zip>23507</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Elena Sinkovskaya, MD</last_name>
      <email>sinkove@evms.edu</email>
    </contact>
    <contact_backup>
      <last_name>Alfred Abuhamad, MD</last_name>
      <email>abuhamaz@evms.edu</email>
    </contact_backup>
    <investigator>
      <last_name>Elena Sinkovskaya, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Alfred Abuhamad, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Seattle Children's Hospital</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98105</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Bhawna Arya, MD</last_name>
      <email>Bhawna.Arya@seattlechildrens.org</email>
    </contact>
    <investigator>
      <last_name>Bhawna Arya, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Stollery Children's Hospital</name>
      <address>
        <city>Edmonton</city>
        <state>Alberta</state>
        <zip>AB T6G 2B7</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Lisa Hornberger, MD</last_name>
      <email>Lisa.Hornberger@albertahealthservices.ca</email>
    </contact>
    <investigator>
      <last_name>Lisa Hornberger, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Canada</country>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>July 14, 2020</study_first_submitted>
  <study_first_submitted_qc>July 14, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 16, 2020</study_first_posted>
  <last_update_submitted>July 18, 2023</last_update_submitted>
  <last_update_submitted_qc>July 18, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 19, 2023</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>Atrioventricular Block</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dexamethasone</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices) will be shared upon reasonable request.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_time_frame>Beginning 9 months and ending 36 months following article publication or as required by a condition of awards and agreements supporting the research.</ipd_time_frame>
    <ipd_access_criteria>The investigator who proposes to use the data will have access to the data upon reasonable request and when a stated purpose and approval by a committee is provided. Requests should be directed to Jill.Buyon@nyulangone.org. To gain access, data requestors will need to sign a data access agreement.</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/NCT04474223
org study id: 20-00363
nct id: NCT04474223
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
Fetal complete (i.e., third degree, 3°) atrioventricular block (AVB), identified in the 2nd
      trimester of pregnancy in an otherwise normally developing heart, is almost universally
      associated with maternal anti-Ro autoantibodies and results in death in a fifth of cases. To
      date treatment of 3° AVB has been ineffective in restoring normal rhythm (NR) which may be
      because current surveillance is limited to once- weekly fetal echocardiograms. It is
      hypothesized that there may be a vital transition period of several hours in which incomplete
      block (2° AVB) may be successfully treated avoiding fully advanced irreversible 3° AVB. To
      optimize the likelihood of timely detection of the transition period this study comprises
      three steps: 1) to risk stratify for high titer anti-Ro antibodies, which are necessary but
      not sufficient to develop fetal AVB; 2) to empower mothers to identify 2° AVB by using fetal
      heart rate and rhythm monitoring (FHRM) at home, and 3) to rapidly treat mothers who detect
      an abnormality by monitoring with an urgent echocardiogram that confirms 2° AVB with the hope
      of reversing 2° AVB before it becomes permanent (3° AVB). In addition, it will be determined
      if FHRM reduces the need for weekly echoes. Although mothers with low titer anti-Ro will not
      be continued in Step 2 and therefore not followed by FHRM, birth ECGs will be collected to
      confirm that low titer antibodies do not confer risk. It is anticipated that this study will
      provide an evidenced based surveillance strategy for those mothers at high risk of having a
      child with 3° AVB.
Fetal complete (3°) atrioventricular block (AVB), identified in the 2nd trimester in an
      otherwise normally developing heart, is almost universally associated with maternal anti-Ro
      autoantibodies, which transcytose the placenta via the trophoblastic IgG receptor, FcγRn. The
      burden of 3° AVB is considerable: perinatal mortality of 18% exceeds that for all non-cardiac
      congenital anomalies combined, and almost all survivors require lifelong cardiac pacing with
      its associated complications. It has been speculated that full expression of conduction
      disease occurs by sequential fetal progression from normal rhythm (NR) to 1° AVB [prolonged
      AV interval assessed by echocardiogram (echo)], to 2° AVB (irregular cardiac rhythm or
      bradycardia), culminating in 3° AVB. Fetal heart rate and rhythm monitoring (FHRM) suggests a
      time interval of ~12 hours for the transition from NR to 3° AVB, albeit the culprit biologic
      processes (inflammation leading to fibrosis) likely initiate prior to clinical detection.
      Anecdotal evidence suggests this transition period, marked by an irregular rhythm and/or
      bradycardia, may be the only window of opportunity for anti-inflammatory treatment to restore
      NR.

      A barrier to preventing progression to 3° AVB is the absence of a technique to accurately
      surveil for the precipitate transition from NR to 3° AVB. Surveillance limited to weekly
      echos (current standard of care) may be too infrequent to detect this transition period when
      treatment is most likely to be effective. We have now obviated this obstacle and shown that
      ambulatory FHRM by the mother at home with confirmation of abnormal findings by echo is not
      only feasible but may afford rapid treatment restoring NR. Combining results from studies
      comprising 275 anti-Ro+ pregnancies, 87% completed monitoring with a false positive rate of
      5%. In 4 cases of 2° AVB identified by FHRM and treated <12h, AVB reversed. Remarkably, no
      cases of 2° or 3° AVB were missed, suggesting mothers can recognize abnormal FHRM, reducing
      or precluding the need for weekly echos.

      The proposed project combines the expertise of fetal cardiologist Bettina F. Cuneo, MD,
      initiator and PI of the FHRM program, and rheumatologist Jill P. Buyon, MD, founder/director
      of the largest extant registry of anti-Ro-mediated AVB, whose research on the pathogenesis
      supports a fetal inflammatory component associated with high-titer antibodies. Participants
      will be referred from 35 sites in 3 sequential Steps: 1) Screening for high titer anti-Ro60
      or Ro52 centrally in Dr. Buyon's lab; 2) Surveillance by FHRM 3x daily and weekly echo; 3)
      Treatment of 2° AVB identified by FHRM confirmed by echo. Feasibility of FHRM supported by
      weekly echo of high-autoantibody-titer mothers will be leveraged to address the efficacy of
      expeditious (<12 h after detection) treatment of 2° AVB as well as the incidence/outcome of
      AV interval prolongation and extra-nodal disease.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Percentage of 2° AVB subjects with NR (1:1 AV conduction) at birth
time frame: up to 25 weeks post-enrollment
description: The presence of NR (normal rhythm) will be determined by electrocardiogram (ECG)
measure: Percentage of 2° AVB subjects who maintain NR at age 1 year.
time frame: 1 year post-birth
description: The presence of NR will be determined by ECG
measure: Percentage of AV interval > 170 msec subjects with NR at birth
time frame: At birth
description: AV intervals will be determined by EKG
measure: Incidences of isolated extra-nodal cardiac disease
time frame: up to 1 year post-birth
description: Extra-nodal cardiac disease includes: Endocardial fibroelastosis, dilated cardiomyopathy, and AV valve insufficiency. Isolated exta-nodal cardiac disease will be determined by echocardiogram.
arm group label: Mothers with Fetuses Who Have 2° AVB or AV interval > 170ms
arm group type: Experimental
intervention type: Drug
intervention name: Dexamethasone
description: In mother in whom 2° AVB or AV interval >170 ms has been diagnosed in the fetus:
Dexamethasone 8 mg po/day for 10 days. Then dexamethasone 4 mg po/ day through 28 weeks 6 days gestational age (GA); then 3 mg/day from 29 wks 0 days to 29 wks 6 days GA; then 2 mg/day until delivery
arm group label: Mothers with Fetuses Who Have 2° AVB or AV interval > 170ms
intervention type: Drug
intervention name: IVIG
description: In a mother in whom 2° AVB has been diagnosed in the fetus:
One dose of IVIG [1g/kg of maternal weight (max dose 70 g)] at diagnosis of 2° AVB (within 12 hours of detection by mother via home monitoring and within 6 hours of confirmation by echocardiogram). A fetal AV interval > 170 ms will not be treated with maternal IVIG, only dexamethasone.
arm group label: Mothers with Fetuses Who Have 2° AVB or AV interval > 170ms
criteria: 
gender: Female
gender based: Yes
gender description: Must be <18 weeks pregnant at the time of enrollment
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jill Buyon, MD
role: Principal Investigator
affiliation: NYU Langone Health
last name: Bettina Cuneo, MD
role: Principal Investigator
affiliation: University of Colorado, Denver
last name: Mala Masson
phone: 212-263-0372
email: mala.masson@nyulangone.org
last name: Jill Buyon, MD
phone: 212-263-0756
email: Jill.Buyon@nyulangone.org,
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
investigator: 
investigator: 
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
contact backup: 
investigator: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
country: Canada
country: United States
responsible party type: Sponsor
mesh term: Atrioventricular Block
mesh term: Dexamethasone
sharing ipd: Yes
ipd description: Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices) will be shared upon reasonable request.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd time frame: Beginning 9 months and ending 36 months following article publication or as required by a condition of awards and agreements supporting the research.
ipd access criteria: The investigator who proposes to use the data will have access to the data upon reasonable request and when a stated purpose and approval by a committee is provided. Requests should be directed to Jill.Buyon@nyulangone.org. To gain access, data requestors will need to sign a data access agreement.