Clinical trial NCT05386173: Effect of Fetal Aortic Valvuloplasty on Outcomes
Official title: Effect of Fetal Aortic Valvuloplasty on Outcomes. A Prospective Observational Cohort Study With a Comparison Cohort
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Congenital Heart Disease
Aortic Valve Stenosis
Fetal Cardiac Disorder
Hypoplastic Left Heart Syndrome
Lead sponsor: Queen Silvia Children's Hospital, Gothenburg, Sweden
Sponsor class: OTHER
Collaborators: name: Swedish Heart Lung Foundation
name: Sahlgrenska University Hospital
First posted: 2022-05-23
Enrollment: 200
Sex: ALL
Minimum age (years): 23
Maximum age (years): 31
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study population consists of fetuses and children with aortic valve stenosis and/or hypoplastic left heart syndrome

Brief summary: In one of the most severe congenital heart defects, hypoplastic left heart syndrome (HLHS), the left ventricle is underdeveloped and the prognosis is worse than in most other heart defects. The underdevelopment can occur gradually during fetal growth caused by a narrowing of the aortic valve. At some international centers, such fetuses are treated with a balloon dilation of the narrowed valve, but there is no scientifically sound evidence that this treatment is effective.

The aim of this study is: 1/ to evaluate whether balloon dilation during the fetal period of a narrowed aortic valve can reduce the risk of the left ventricle becoming underdeveloped and the baby being born with a so-called univentricular heart (HLHS); 2/ to investigate whether such treatment improves the prognosis for this group of children with a very complex and severe heart defect and 3/ to also describe side effects and risks in fetuses and mothers of the fetal procedure.

Detailed description: Routinely collected pre- and postnatal clinical data will be entered into a digital database and echocardiographic examinations will be uploaded to a server. A core lab will measure and analyze all echocardiographic examinations according to protocol. The growth of the left heart structures and the postnatal outcome will be compared between the intervention and non-intervention groups.

The decision whether a fetal balloon dilatation shall be attempted is not part of the study protocol. The number of examinations of mother/fetus/infant in this study is not different from the number of examinations that will be recommended for someone choosing not to be part of this study. Participation in the study does not affect the care and treatment mothers and fetuses are receiving during pregnancy, nor how the infant is examined and treated after birth.

Eligibility criteria: Inclusion Criteria:

A. All of the following echocardiographic criteria need to be satisfied between 23+0 and 31+6 weeks (z-scores according to Schneider et al):

1. Aortic valve stenosis with antegrade flow through the valve
2. Predominantly left-to-right shunt at the atrial level
3. Predominantly retrograde flow in the aortic arch between the first two brachiocephalic vessels
4. Qualitatively depressed left ventricular function
5. Left ventricular end-diastolic diameter Z-score \> ±0
6. Left ventricular inlet length in diastole :

   1. Gestational age ≤ 24+6: Z-score \> ±0
   2. Gestational age 25+0 to 27+6: Z-score \> -0.75
   3. Gestational age ≥ 28+0: Z-score \> -1.50
7. Mitral valve diameter in diastole Z-score \> -2.0

B. All of the following postnatal treatment options need to be available: 1. Surgical or catheter based aortic valvotomy 2. Ross-Konno surgery 3. Norwood or hybrid stage-one surgery

Exclusion Criteria:

1. Any associated cardiac defect except persistent left superior vena cava and coarctation of the aorta
2. Any significant (i.e. that might influence outcome) extracardiac anomaly and/or known chromosomal aberration. Also, if such a condition is present at inclusion but diagnosed only after birth the case will be retrospectively excluded.

Primary outcomes:
measure: Transplantation-free survival
timeFrame: Follow-up from study inclusion during fetal life until 2 years postnatal age
Secondary outcomes:
measure: Intervention-related fetal death
timeFrame: From the time of fetal intervention until 24 hours after the intervention
measure: Fetal death not directly related to the intervention
timeFrame: From 24 hours after fetal intervention until fetal death, up to 20 weeks after study inclusion.
measure: Maternal complications to fetal intervention procedure
timeFrame: From time of fetal intervention until 24 hours after the intervention
measure: Preterm delivery
timeFrame: From time of fetal intervention until 37 weeks gestational age, maximum 14 weeks
measure: Fetal left heart growth
timeFrame: From the date of study inclusion until just before the first postnatal catheter or surgical intervention, or death, whichever comes first, total time frame 7 months
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: Fetal Cardiovascular Program, University of California San Francisco
state: California
city: Columbus
country: United States
facility: Congenital Heart Collaborative, Nationwide Children's Hospital
state: Ohio
city: Linz
country: Austria
facility: Kinderherzzentrum Linz
city: Toronto
country: Canada
facility: The Hospital for Sick Children Toronto
city: Helsinki
country: Finland
facility: Department of Paediatric Cardiology, Helsinki University Children's Hospital
city: Bonn
country: Germany
facility: Pediatric Cardiology - University Hospital Bonn
city: Heidelberg
country: Germany
facility: Department of Pediatric and Congenital Cardiology, University of Heidelberg
city: Munich
country: Germany
facility: University hospital Technical university, mother- and-child center
city: Warsaw
country: Poland
facility: Department of Perinatal Cardiology and Congenital Anomalies, Centre of Postgraduate Medical Education.
city: Madrid
country: Spain
facility: Fetal Medicine Unit, Dept. Obstetrics & Gynecology University Hospital 12 de Octubre
city: Lund
country: Sweden
facility: Department of Pediatric Cardiology, Skane University Hospital
city: Stockholm
country: Sweden
facility: Department of pediatric cardiology, Karolinska Institute
city: Umeå
country: Sweden
facility: Department of Pediatrics, Umeå University Hospital
Study officials:
References: