Effect of Fetal Aortic Valvuloplasty on Outcomes

Congenital Heart Disease Clinical Trial

— FASSprosp  

Official title:

Effect of Fetal Aortic Valvuloplasty on Outcomes. A Prospective Observational Cohort Study With a Comparison Cohort

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05386173
• Other study ID #: FASSprosp
• Status: Recruiting
• Start date: January 1, 2021
• Est. completion date: December 31, 2029

Study information

• Verified date: November 2023
• Source: Queen Silvia Children's Hospital, Gothenburg, Sweden
• Contact: Mats Mellander, Dr, Prof
• Phone: 0046705530606
• Email: mats.mellander[@]vgregion.se
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: December 31, 2029
• Est. primary completion date: December 31, 2029
• Accepts healthy volunteers: No
• Gender: All
• Age group: 23 Weeks to 31 Weeks

Eligibility

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.

Related Conditions & MeSH terms

• Aortic Valve Stenosis
• Congenital Heart Disease
• Fetal Cardiac Disorder
• Heart Defects, Congenital
• Heart Diseases
• Hypoplastic Left Heart Syndrome

Intervention

Procedure:
• Fetal aortic balloon dilatation
Fetal valvuloplasty will be performed as described in Arzt W, Wertaschnigg D, Veit I, Klement F, Gitter R, Tulzer G. Intrauterine aortic valvuloplasty in fetuses with critical aortic stenosis: experience and results of 24 procedures. Ultrasound Obstet Gynecol. 2011;37:689-695. with minor variations between centers involved. Technical success is defined as improved forward flow and/or new aortic regurgitation.

Locations

Country	Name	City	State
Austria	Kinderherzzentrum Linz	Linz
Canada	The Hospital for Sick Children Toronto	Toronto
Finland	Department of Paediatric Cardiology, Helsinki University Children's Hospital	Helsinki
Germany	Pediatric Cardiology - University Hospital Bonn	Bonn
Germany	Department of Pediatric and Congenital Cardiology, University of Heidelberg	Heidelberg
Germany	University hospital Technical university, mother- and-child center	Munich
Poland	Department of Perinatal Cardiology and Congenital Anomalies, Centre of Postgraduate Medical Education.	Warsaw
Spain	Fetal Medicine Unit, Dept. Obstetrics & Gynecology University Hospital 12 de Octubre	Madrid
Sweden	Department of Pediatric Cardiology, Skane University Hospital	Lund
Sweden	Department of pediatric cardiology, Karolinska Institute	Stockholm
Sweden	Department of Pediatrics, Umeå University Hospital	Umeå
United States	Congenital Heart Collaborative, Nationwide Children's Hospital	Columbus	Ohio
United States	Fetal Cardiovascular Program, University of California San Francisco	San Francisco	California

Sponsors (3)

Lead Sponsor	Collaborator
Queen Silvia Children's Hospital, Gothenburg, Sweden	Sahlgrenska University Hospital, Sweden, Swedish Heart Lung Foundation

Countries where clinical trial is conducted

United States,  Austria,  Canada,  Finland,  Germany,  Poland,  Spain,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Transplantation-free survival	Transplantation-free survival from fetal diagnosis to 2 years postnatal age with a biventricular circulation without pulmonary hypertension at that time. Absence of pulmonary hypertension is defined as a TR max velocity = 2.8 m/s with no other echocardiographic signs of pulmonary hypertension and/or catheter data showing a mean pulmonary arterial pressure <25 mmHg.	Follow-up from study inclusion during fetal life until 2 years postnatal age
Secondary	Intervention-related fetal death	Intervention-related fetal death (defined as fetal death within 24 hours of procedure)	From the time of fetal intervention until 24 hours after the intervention
Secondary	Fetal death not directly related to the intervention	Fetal death not directly related to the intervention, except termination of pregnancy	From 24 hours after fetal intervention until fetal death, up to 20 weeks after study inclusion.
Secondary	Maternal complications to fetal intervention procedure	Maternal complications to procedure requiring intensive care or resulting in maternal death	From time of fetal intervention until 24 hours after the intervention
Secondary	Preterm delivery	Preterm delivery before 37 weeks gestational age	From time of fetal intervention until 37 weeks gestational age, maximum 14 weeks
Secondary	Fetal left heart growth	Fetal left heart growth as measured with dimensions expressed a z-scores of the mitral valve diameter, left ventricular inlet length and aortic valve diameter	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