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

Overview

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.

Interventions

• Drug Dexamethasone
  All management decisions are made by the primary physician and may include: 1) no treatment with dexamethasone or 2) treatment with dexamethasone from the time of enrollment
• Other No Dexamethasone
  All management decisions are made by the primary physician and may include: 1) no treatment with dexamethasone or 2) treatment with dexamethasone from the time of enrollment

Primary outcome measures

• Freedom from cardiac death ≥1 year of life [Time frame: up to 12 months]

Secondary outcome measures (11)

• Proportion of participants with fetal and neonatal death and their causes/factors [Time frame: 1 month]
• Proportion of participants with change in prenatal treatment [Time frame: up to 6 months]
• Proportion of secondarily treated patients (initially untreated group 1 cases) [Time frame: up to 6 months]
• Proportion of serious pregnancy outcomes (IUFD, IUGR <3rd percentile, delivery <35 weeks) [Time frame: up to 6 months]
• Proportion of patients/group with progression from incomplete to complete AVB by 1 year [Time frame: Fetal diagnosis to 12 months]
• Proportion of maternal serious adverse events and outcomes [Time frame: Fetal diagnosis to 12 months]
• Average gestational age at birth [Time frame: Birth]
• Average birth weight [Time frame: Birth]
• Freedom from permanent pacemaker implantation from birth to 1 year of life [Time frame: Birth to 12 months]
• Prevalence of significant heart failure (HF score, echo, HF treatment) at 1 year of life [Time frame: 12 months]
• Proportion of children with moderate/severe neuro-developmental delay at 12-18 months [Time frame: 12-18 months]

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)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Study design

Observational model

Cohort

Study locations

United States · 12 centers

• Phoenix Children's Hospital — Phoenix
• University of California San Francisco — San Francisco
• Children's Hospital Colorado — Denver
• Children's National Medical Center — Washington D.C.
• Johns Hopkins All Children's Hospital — St. Petersburg
• Children's Mercy Kansas City — Kansas City
• Boston Children's Hospital — Boston
• The Children's Heart Clinic/Children's Minnesota — Minneapolis
• … and 4 more centers

Sweden · 3 centers

• Queen Silvia Children's Hospital — Gothenburg
• Skane University Hospital in Lund — Lund
• Karolinska University Hospital, Astrid Lindgen Childrens Hospital — Solna

Canada · 2 centers

• IWK Nova Scotia Health — Halifax
• The Hospital for Sick Children — Toronto

Japan · 2 centers

• Kanagawa Children's Medical Center — Kanagawa
• Shizuoka Children's Hospital — Shizuoka

Bulgaria · 1 center

• National Heart Hospital — Sofia

Finland · 1 center

• Hospital District of Helsinki and Uusimaa — Helsinki

France · 1 center

• Grenoble University Hospital — Grenoble

Germany · 1 center

• University of Bonn — Bonn

Hong Kong · 1 center

• Hong Kong Children's Hospital — Ngau Tau Kok

Netherlands · 1 center

• Leiden University Medical Center - LUMC — Leiden

Poland · 1 center

• Centre of Postgraduate Medical Education Poland — Warsaw

Taiwan · 1 center

• Taiji Clinic — Taipei

Identifiers

NCT: NCT04559425 · 1000065121

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗