Clinical trial NCT04559425: Slow Heart Registry of Fetal Immune-mediated High Degree Heart Block
Official title: Slow Heart Registry: A Prospective Observational Cohort Study of Fetal Immune-mediated High Degree Heart Block
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Heart Block Complete
Heart Block Second Degree
Keywords: fetal
heart block
anti-Ro antibodies
steroids
outcome
Lead sponsor: The Hospital for Sick Children
Sponsor class: OTHER
First posted: 2020-09-22
Enrollment: 350
Sex: FEMALE
Minimum age (years): 16
Maximum age (years): 50
Standard ages: CHILD
ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Enrollment into the SLOW HEART Registry is possible within maximally 8 days of the fetal heart block diagnosis and a management decision to treat or not to treat. If a mother elects participation in the Registry, her treating physician will continue to provide care in accordance with clinical practice at the site and will decide all therapy including close observation without or with immediate steroid treatment.

Brief summary: Few studies are specifically designed to address health concerns that are already relevant during pregnancy. The consequence is a lack of evidence on best clinical practice. This includes mothers and their babies when pregnancy is complicated by an abnormally slow heart rate due to maternal antibody-mediated heart disease in the unborn baby (fetus). Since the late seventies, it has been possible to detect and monitor fetal disease by ultrasound images and to treat selected conditions with pharmaceuticals administered via the mother. To this day, physicians need to make decisions about the management of such pregnancies without evidence from prospective clinical trials on drug efficacy and safety. The SLOW HEART REGISTRY is a multi-centered prospective observational study that will address the knowledge gap to guide future management of high-degree immune-mediated heart block to the best of care. The study seeks to establish an international database of the management and outcome of affected fetuses, to be used to publish information on the results of currently available prenatal care and to evaluate the need for additional research.

Detailed description: The SLOW HEART REGISTRY is a multi-centered prospective observational study of fetuses diagnosed with high-degree immune-mediated atrio-ventricular heart block (AVB). The study seeks to establish an international database of the management and outcome of affected fetuses, to be used to publish information on the results of currently available prenatal care and to evaluate the need for additional research.

The study aims are to document the outcome of patients diagnosed prenatally with immune-mediated 2nd or 3rd degree AVB irrespective of the primary choice of prenatal care.

The primary objective will be to determine the rate of transplant-free survival to 1 year of life of fetuses with AVB based on the prenatal management decision:

* Cohort 1: Fetuses not treated with fluorinated glucocorticoids
* Cohort 2: Fetuses treated with fluorinated glucocorticoids from the time of immune-mediated AVB diagnosis.

Secondary objectives will be to determine:

1. the evolution of clinical findings from AVB diagnosis to birth (AV conduction; fetal heart rate; other NL manifestations; fetal growth; effusions/hydrops) between cohorts;
2. the need of new/additional treatment (steroids; beta-mimetics; IVIG) to birth;
3. gestational age and weight at birth;
4. postnatal management (pacing; steroids; IVIG); and
5. clinical evolution from birth to 1-3 years of life (cardiac function; developmental milestones; infant growth; health).

Prevalence of relevant fetal-maternal events and complications (death; IUGR; morbidity) between the study cohorts will also be determined.

All management is decided by the treating center and physicians in accordance to institutional guidelines and clinical findings. Patient enrollment in the SLOW HEART REGISTRY is possible within up to 8 days of the initial management decision.

Participation in this prospective observational cohort study requires site REB approval and an executed legal contract with the primary investigator/SickKids Hospital, Toronto.

Eligibility criteria: Inclusion Criteria:

* Written informed maternal consent to participate in the Slow Heart Registry
* High-degree (2nd; 2:1; 2nd-3rd or 3rd degree) AVB diagnosed ≤ 32+0 weeks with or without hydrops
* Enrollment within maximally 8 days of high-degree AVB diagnosis
* Positive or pending anti-Ro/La antibody test results at the time of enrollment

Exclusion Criteria:

* AVB associated with major CHD (e.g. left atrial isomerism, cc-TGA)
* AVB with known negative anti-Ro and/or La antibody test result at enrollment
* 1st degree AVB
* Sinus bradycardia with normal 1:1 AV conduction
* Blocked atrial bigeminy (irregular atrial rate with failure of AV conduction of the premature atrial beat)
* Primary delivery for postnatal treatment
* Maternal-fetal conditions (other than cardiac NL) associated with high odds of premature delivery or death (e.g. renal failure, significant infectious diseases, major extracardiac anomalies, PROM, etc.)
* Preexisting maternal mental disorder (e.g. bipolar, mania, severe depression, substance abuse)
* Poorly controlled insulin-dependent diabetes (HbA1c \>7%) at CAVB diagnosis
* Oligohydramnios (deepest/maximal vertical pocket \<2 cm)
* Severe IUGR (estimated fetal weight \<3rd percentile)

Primary outcomes:
measure: Freedom from cardiac death ≥1 year of life
timeFrame: up to 12 months
Secondary outcomes:
measure: Proportion of participants with fetal and neonatal death and their causes/factors
timeFrame: 1 month
measure: Proportion of participants with change in prenatal treatment
timeFrame: up to 6 months
measure: Proportion of secondarily treated patients (initially untreated group 1 cases)
timeFrame: up to 6 months
measure: Proportion of serious pregnancy outcomes (IUFD, IUGR <3rd percentile, delivery <35 weeks)
timeFrame: up to 6 months
measure: Proportion of patients/group with progression from incomplete to complete AVB by 1 year
timeFrame: Fetal diagnosis to 12 months
measure: Proportion of maternal serious adverse events and outcomes
timeFrame: Fetal diagnosis to 12 months
measure: Average gestational age at birth
timeFrame: Birth
measure: Average birth weight
timeFrame: Birth
measure: Freedom from permanent pacemaker implantation from birth to 1 year of life
timeFrame: Birth to 12 months
measure: Prevalence of significant heart failure (HF score, echo, HF treatment) at 1 year of life
timeFrame: 12 months
measure: Proportion of children with moderate/severe neuro-developmental delay at 12-18 months
timeFrame: 12-18 months
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Phoenix Children's Hospital
state: Arizona
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Denver
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Washington
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Saint Petersburg
country: United States
facility: Johns Hopkins All Children's Hospital
state: Florida
city: Kansas City
country: United States
facility: Children's Mercy Kansas City
state: Kansas
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Minneapolis
country: United States
facility: The Children's Heart Clinic/Children's Minnesota
state: Minnesota
city: New York
country: United States
facility: Columbia University (New York)
state: New York
city: Houston
country: United States
facility: Texas Children's Hospital
state: Texas
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Sofia
country: Bulgaria
facility: National Heart Hospital
city: Halifax
country: Canada
facility: IWK Nova Scotia Health
state: Nova Scotia
city: Toronto
country: Canada
facility: The Hospital for Sick Children
city: Helsinki
country: Finland
facility: Hospital District of Helsinki and Uusimaa
city: Grenoble
country: France
facility: Grenoble University Hospital
city: Bonn
country: Germany
facility: University of Bonn
city: Ngau Tau Kok
country: Hong Kong
facility: Hong Kong Children's Hospital
city: Kanagawa
country: Japan
facility: Kanagawa Children's Medical Center
city: Shizuoka
country: Japan
facility: Shizuoka Children's Hospital
city: Leiden
country: Netherlands
facility: Leiden University Medical Center - LUMC
city: Warsaw
country: Poland
facility: Centre of Postgraduate Medical Education Poland
city: Gothenburg
country: Sweden
facility: Queen Silvia Children's Hospital
city: Lund
country: Sweden
facility: Skane University Hospital in Lund
city: Solna
country: Sweden
facility: Karolinska University Hospital, Astrid Lindgen Childrens Hospital
city: Taipei
country: Taiwan
facility: Taiji Clinic
Study officials:
affiliation: The Hospital for Sick Children, Toronto
name: Edgar Jaeggi, MD
role: PRINCIPAL_INVESTIGATOR
References: