RecruitingPhase 3NCT04474223

Surveillance and Treatment to Prevent Fetal Atrioventricular Block Likely to Occur Quickly (STOP BLOQ)


Sponsor

NYU Langone Health

Enrollment

1,300 participants

Start Date

Aug 1, 2020

Study Type

INTERVENTIONAL

Conditions

Summary

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.


Eligibility

Sex: FEMALEMin Age: 18 Years

Inclusion Criteria9

  • Provision of signed and dated informed consent form
  • Stated willingness to comply with all study procedures and availability for the duration of the study
  • Be <18 weeks pregnant at the time of enrollment
  • Titer of anti-Ro 52 or 60 antibodies ≥1,000 EU
  • Any positive titer of anti-Ro if a history of a previously affected child
  • Ability to take oral medication and be willing to adhere to the dexamethasone and IVIG protocols.
  • Ability to perform Doppler fetal heart rate and rhythm monitoring in the ambulatory setting,
  • Ability to send an audiotext message by cell phone therefore the participant will be informed that they need a phone with texting capabilities. Located within 6 hours drive of the participating pediatric cardiology site
  • Be ≥18 years of age

Exclusion Criteria6

  • Multi-fetal pregnancy
  • Known allergic reactions to components of IVIG, or dexamethasone or maternal IgA deficiency
  • Fetal conduction system disease already present in the current pregnancy
  • Any women who in the opinion of the investigator cannot understand the consent form or be able to perform thrice daily home monitoring or recognize an abnormal fetal heart rate or rhythm
  • Women prisoners
  • Treatment with >20 mg/prednisone q day or with any dose of fluorinated steroids at enrollment

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Interventions

DRUGDexamethasone

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

DRUGIVIG

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.


Locations(24)

Phoenix Children's Hospital/Dignity Health

Phoenix, Arizona, United States

University of California - Los Angeles (UCLA)

Los Angeles, California, United States

Stanford University

Palo Alto, California, United States

University of California-San Francisco

San Francisco, California, United States

University of Colorado, Denver (UCD)

Aurora, Colorado, United States

Yale University School of Medicine

New Haven, Connecticut, United States

Children's National Medical Center/George Washington University

Washington D.C., District of Columbia, United States

University of Kentucky / Kentucky Children's Hospital

Lexington, Kentucky, United States

University of Louisville / Norton Children's Hospital

Louisville, Kentucky, United States

University of Michigan / C. S. Mott Children's Hospital

Ann Arbor, Michigan, United States

Children's Hospital of Minnesota

Minneapolis, Minnesota, United States

Perinatal Associates of New Mexico

Rio Rancho, New Mexico, United States

NYU Langone Health

New York, New York, United States

Mount Sinai

New York, New York, United States

Columbia University Medical Center

New York, New York, United States

UH Rainbow Babies / Children's Hospital

Cleveland, Ohio, United States

Cleveland Clinic Lerner College of Medicine

Cleveland, Ohio, United States

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Baylor College of Medicine

Houston, Texas, United States

University of Utah Health

Salt Lake City, Utah, United States

University of Vermont Children's Hospital

Burlington, Vermont, United States

Eastern Virginia Medical School (EVMS)

Norfolk, Virginia, United States

Seattle Children's Hospital

Seattle, Washington, United States

Stollery Children's Hospital

Edmonton, Alberta, Canada

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NCT04474223