NCT04474223

Brief 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.

Trial Health

80
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
1,300

participants targeted

Target at P75+ for phase_3

Timeline
39mo left

Started Aug 2020

Longer than P75 for phase_3

Geographic Reach
2 countries

24 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress65%
Aug 2020Jun 2029

First Submitted

Initial submission to the registry

July 14, 2020

Completed
2 days until next milestone

First Posted

Study publicly available on registry

July 16, 2020

Completed
16 days until next milestone

Study Start

First participant enrolled

August 1, 2020

Completed
8.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 31, 2028

Expected
6 months until next milestone

Study Completion

Last participant's last visit for all outcomes

June 30, 2029

Last Updated

April 9, 2025

Status Verified

April 1, 2025

Enrollment Period

8.4 years

First QC Date

July 14, 2020

Last Update Submit

April 8, 2025

Conditions

Outcome Measures

Primary Outcomes (1)

  • Percentage of 2° AVB subjects with NR (1:1 AV conduction) at birth

    The presence of NR (normal rhythm) will be determined by electrocardiogram (ECG)

    up to 25 weeks post-enrollment

Secondary Outcomes (3)

  • Percentage of 2° AVB subjects who maintain NR at age 1 year.

    1 year post-birth

  • Percentage of AV interval > 170 msec subjects with NR at birth

    At birth

  • Incidences of isolated extra-nodal cardiac disease

    up to 1 year post-birth

Study Arms (1)

Mothers with Fetuses Who Have 2° AVB or AV interval > 170ms

EXPERIMENTAL
Drug: DexamethasoneDrug: IVIG

Interventions

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

Mothers with Fetuses Who Have 2° AVB or AV interval > 170ms
IVIGDRUG

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.

Mothers with Fetuses Who Have 2° AVB or AV interval > 170ms

Eligibility Criteria

Age18 Years+
Sexfemale(Gender-based eligibility)
Gender Eligibility DetailsMust be \<18 weeks pregnant at the time of enrollment
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (24)

Phoenix Children's Hospital/Dignity Health

Phoenix, Arizona, 85016, United States

RECRUITING

University of California - Los Angeles (UCLA)

Los Angeles, California, 90095, United States

RECRUITING

Stanford University

Palo Alto, California, 94305, United States

RECRUITING

University of California-San Francisco

San Francisco, California, 94143, United States

RECRUITING

University of Colorado, Denver (UCD)

Aurora, Colorado, 80204, United States

RECRUITING

Yale University School of Medicine

New Haven, Connecticut, 06510, United States

RECRUITING

Children's National Medical Center/George Washington University

Washington D.C., District of Columbia, 20010, United States

RECRUITING

University of Kentucky / Kentucky Children's Hospital

Lexington, Kentucky, 40536, United States

RECRUITING

University of Louisville / Norton Children's Hospital

Louisville, Kentucky, 40202, United States

NOT YET RECRUITING

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

Ann Arbor, Michigan, 48109, United States

RECRUITING

Children's Hospital of Minnesota

Minneapolis, Minnesota, 55404, United States

RECRUITING

Perinatal Associates of New Mexico

Rio Rancho, New Mexico, 87124, United States

RECRUITING

NYU Langone Health

New York, New York, 10016, United States

RECRUITING

Mount Sinai

New York, New York, 10029, United States

RECRUITING

Columbia University Medical Center

New York, New York, 10032, United States

RECRUITING

UH Rainbow Babies / Children's Hospital

Cleveland, Ohio, 44106, United States

RECRUITING

Cleveland Clinic Lerner College of Medicine

Cleveland, Ohio, 44195, United States

RECRUITING

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

RECRUITING

Baylor College of Medicine

Houston, Texas, 77030, United States

RECRUITING

University of Utah Health

Salt Lake City, Utah, 84102, United States

RECRUITING

University of Vermont Children's Hospital

Burlington, Vermont, 05401, United States

RECRUITING

Eastern Virginia Medical School (EVMS)

Norfolk, Virginia, 23507, United States

RECRUITING

Seattle Children's Hospital

Seattle, Washington, 98105, United States

NOT YET RECRUITING

Stollery Children's Hospital

Edmonton, Alberta, AB T6G 2B7, Canada

NOT YET RECRUITING

MeSH Terms

Conditions

Atrioventricular Block

Interventions

DexamethasoneImmunoglobulins, Intravenous

Condition Hierarchy (Ancestors)

Heart BlockArrhythmias, CardiacHeart DiseasesCardiovascular DiseasesCardiac Conduction System DiseasePathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

PregnadienetriolsPregnadienesPregnanesSteroidsFused-Ring CompoundsPolycyclic CompoundsSteroids, FluorinatedImmunoglobulin GImmunoglobulin IsotypesAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulins

Study Officials

  • Jill Buyon, MD

    NYU Langone Health

    PRINCIPAL INVESTIGATOR
  • Bettina Cuneo, MD

    University of Colorado, Denver

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Study Design

Study Type
interventional
Phase
phase 3
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 14, 2020

First Posted

July 16, 2020

Study Start

August 1, 2020

Primary Completion (Estimated)

December 31, 2028

Study Completion (Estimated)

June 30, 2029

Last Updated

April 9, 2025

Record last verified: 2025-04

Data Sharing

IPD Sharing
Will share

Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices) will be shared upon reasonable request.

Shared Documents
STUDY PROTOCOL, SAP
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.
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.

Locations