Trial Review

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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT05698277




Registration number
NCT05698277
Ethics application status
Date submitted
18/12/2022
Date registered
26/01/2023
Date last updated
30/11/2023

Titles & IDs
Public title
Automated Fetal Cardiac Function in Babies Affected by Heart Diseases
Scientific title
Automated Fetal Cardiac Function Parameters in Congenital Heart Disease
Secondary ID [1] 0 0
2022/ETH00943
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Congenital Heart Defect 0 0
Cardiac Function 0 0
Condition category
Condition code
Cardiovascular 0 0 0 0
Coronary heart disease
Cardiovascular 0 0 0 0
Other cardiovascular diseases
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Observational
Patient registry
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
Diagnosis / Prognosis - Automated fetal cardiac function evaluation

Cases - Singleton pregnancies affected by congenital heart disease

Controls - Singleton healthy pregnancies


Diagnosis / Prognosis: Automated fetal cardiac function evaluation
Evaluation of ultrasound parameters by automated algorithms.
Ultrasound assessed parameters are:
Pulsed wave Doppler Modified Left and Right Myocardial performance indices
Spatio-temporal image correlation Tricuspid, Mitral and Septal Annular Plane Systolic Excursion
Intervention code [1] 0 0
Diagnosis / Prognosis
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Automated PWD-MPI comparing fetuses affected by congenital heart disease (CHD) to reference values across the fetal healthy population.
Timepoint [1] 0 0
Measurements undertaken within the range 27+6 - 29+6 gestational weeks
Primary outcome [2] 0 0
Automated STIC Tricuspid, Mitral and Septal Annular Plane Systolic Excursion comparing fetuses affected by congenital heart disease to reference values across the fetal healthy population.
Timepoint [2] 0 0
Measurements undertaken within the range 27+6 - 29+6 gestational weeks
Primary outcome [3] 0 0
Automated PWD-MPI comparing fetuses affected by congenital heart disease (CHD) to reference values across the fetal healthy population.
Timepoint [3] 0 0
Measurements undertaken within the range 34+6 - 36+6 gestational weeks
Primary outcome [4] 0 0
Automated STIC Tricuspid, Mitral and Septal Annular Plane Systolic Excursion comparing fetuses affected by congenital heart disease to reference values across the fetal healthy population.
Timepoint [4] 0 0
Measurements undertaken within the range 34+6 - 36+6 gestational weeks
Primary outcome [5] 0 0
Automated PWD-MPI comparing fetuses affected by congenital heart disease (CHD) to reference values across the fetal healthy population.
Timepoint [5] 0 0
Measurements undertaken within the range 27+6 - 29+6 gestational weeks and within the range 34+6 - 36+6 gestational weeks
Primary outcome [6] 0 0
Automated STIC Tricuspid, Mitral and Septal Annular Plane Systolic Excursion comparing fetuses affected by congenital heart disease (CHD) to reference values across the fetal healthy population.
Timepoint [6] 0 0
Measurements undertaken within the range 27+6 - 29+6 gestational weeks and within the range 34+6 - 36+6 gestational weeks
Secondary outcome [1] 0 0
Predictive value of Modified Cardiovascular Profile Score in hydrops (Adding Automated PWD-MPI to the classical cardiovascular profile score).
Timepoint [1] 0 0
Measurements undertaken within the range 27+6 - 29+6 gestational weeks.
Secondary outcome [2] 0 0
Predictive value of Modified Cardiovascular Profile Score in hydrops (Adding Automated PWD-MPI to the classical cardiovascular profile score).
Timepoint [2] 0 0
Measurements undertaken within the range 34+6 - 36+6 gestational weeks.
Secondary outcome [3] 0 0
Predictive value of Modified Cardiovascular Profile Score in hydrops (Adding Automated STIC Tricuspid, Mitral and Septal Annular Plane Systolic Excursion to the classical cardiovascular profile score).
Timepoint [3] 0 0
Measurements undertaken within the range 27+6 - 29+6 gestational weeks.
Secondary outcome [4] 0 0
Predictive value of Modified Cardiovascular Profile Score in hydrops (Adding Automated STIC Tricuspid, Mitral and Septal Annular Plane Systolic Excursion to the classical cardiovascular profile score).
Timepoint [4] 0 0
Measurements undertaken within the range 34+6 - 36+6 gestational weeks.
Secondary outcome [5] 0 0
Predictive value of Modified Cardiovascular Profile Score in hydrops (Adding Automated PW-MPI and STIC Tricuspid, Mitral and Septal Annular Plane Systolic Excursion to the classical cardiovascular profile score).
Timepoint [5] 0 0
Measurements undertaken within the range 27+6 - 29+6 gestational weeks.
Secondary outcome [6] 0 0
Predictive value of Modified Cardiovascular Profile Score in hydrops (Adding Automated PW-MPI and STIC Tricuspid, Mitral and Septal Annular Plane Systolic Excursion to the classical cardiovascular profile score).
Timepoint [6] 0 0
Measurements undertaken within the range 34+6 - 36+6 gestational weeks.

Eligibility
Key inclusion criteria
- Inclusion criteria for the CHD Group are as follows: singleton pregnancies;
gestational age between 19+6 and 36+6 weeks gestation, determined by the last
menstrual period and confirmed by first trimester ultrasound; isolated congenital
cardiac anomaly diagnosed.

- Inclusion criteria for the Control Group are as follows: singleton pregnancies;
gestational age between 19+6 and 27+6 weeks gestation, determined by the last
menstrual period and confirmed by first trimester ultrasound; no congenital cardiac
anomaly diagnosed
Minimum age
18 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Exclusion Criteria common to the 2 groups (Cases and Controls):

- Fetuses whose mothers have comorbidities that have been proven to potentially affect
cardiac function including:

- intrahepatic cholestasis

- pre-gestational and gestational diabetes

- preeclampsia

- growth restricted fetuses defined as estimated fetal weight or abdominal
circumference <3rd percentile for GA

- Fetuses with other structural extracardiac anomalies at ultrasound examination

- Fetuses affected by any diagnosed genetic abnormalities

Study design
Purpose
Duration
Selection
Timing
Prospective
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/05/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/02/2028
Actual
Sample size
Target
495
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Royal Hospital for Women - Sydney
Recruitment postcode(s) [1] 0 0
- Sydney
Recruitment outside Australia
Country [1] 0 0
Israel
State/province [1] 0 0
Tel Aviv
Country [2] 0 0
Italy
State/province [2] 0 0
L'Aquila
Country [3] 0 0
Italy
State/province [3] 0 0
Milan
Country [4] 0 0
Italy
State/province [4] 0 0
Trieste
Country [5] 0 0
Mayotte
State/province [5] 0 0
Mamoudzou
Country [6] 0 0
Poland
State/province [6] 0 0
Kraków

Funding & Sponsors
Primary sponsor type
Other
Name
Anna Erenbourg
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Centre Hospitalier de Mayotte
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Vittore Buzzi Children's Hospital
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
San Salvatore Hospital of L'Aquila
Address [3] 0 0
Country [3] 0 0
Other collaborator category [4] 0 0
Other
Name [4] 0 0
Institute for Maternal and Child Health IRCCS Burlo Garofolo
Address [4] 0 0
Country [4] 0 0
Other collaborator category [5] 0 0
Other
Name [5] 0 0
Sheba Medical Center
Address [5] 0 0
Country [5] 0 0
Other collaborator category [6] 0 0
Other
Name [6] 0 0
Clinic of Fetal Echocardiography, Medical Centre UJASTEK
Address [6] 0 0
Country [6] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
The goal of this international multicentre prospective observational cohort study with a
nested case-control study is to test some automated fetal heart functional parameters in
healthy babies compared to those affected by a congenital heart condition.

The main questions it aims to answer are:

- If there is a significant difference between the two populations of infants

- Whether these parameters could significantly improve the predictive value of actual
cardiovascular profile score to predict hydrops Participants will be offered two
automated cardiac function assessments between 27+6 and 29+6 gestational weeks and
between 34+6 and 36+6 weeks of gestation. Functional parameters will be compared between
the two study groups and evaluated over time.
Trial website
https://clinicaltrials.gov/ct2/show/NCT05698277
Trial related presentations / publications
Wu W, He J, Shao X. Incidence and mortality trend of congenital heart disease at the global, regional, and national level, 1990-2017. Medicine (Baltimore). 2020 Jun 5;99(23):e20593. doi: 10.1097/MD.0000000000020593.
Crispi F, Sepulveda-Martinez A, Crovetto F, Gomez O, Bijnens B, Gratacos E. Main Patterns of Fetal Cardiac Remodeling. Fetal Diagn Ther. 2020;47(5):337-344. doi: 10.1159/000506047. Epub 2020 Mar 26.
Walter C, Soveral I, Bartrons J, Escobar MC, Carretero JM, Quirado L, Gomez O, Sanchez-de-Toledo J. Comprehensive Functional Echocardiographic Assessment of Transposition of the Great Arteries: From Fetus to Newborn. Pediatr Cardiol. 2020 Apr;41(4):687-694. doi: 10.1007/s00246-019-02279-w. Epub 2020 Jan 10.
Guirado L, Crispi F, Masoller N, Bennasar M, Marimon E, Carretero J, Gratacos E, Martinez JM, Friedberg MK, Gomez O. Biventricular impact of mild to moderate fetal pulmonary valve stenosis. Ultrasound Obstet Gynecol. 2018 Mar;51(3):349-356. doi: 10.1002/uog.17456.
Inamura N, Taketazu M, Smallhorn JF, Hornberger LK. Left ventricular myocardial performance in the fetus with severe tricuspid valve disease and tricuspid insufficiency. Am J Perinatol. 2005 Feb;22(2):91-7. doi: 10.1055/s-2005-837739.
Lasa JJ, Tian ZY, Guo R, Rychik J. Perinatal course of Ebstein's anomaly and tricuspid valve dysplasia in the fetus. Prenat Diagn. 2012 Mar;32(3):245-51. doi: 10.1002/pd.2939.
Wohlmuth C, Wertaschnigg D, Wieser I, Arzt W, Tulzer G. Tissue Doppler imaging in fetuses with aortic stenosis and evolving hypoplastic left heart syndrome before and after fetal aortic valvuloplasty. Ultrasound Obstet Gynecol. 2016 May;47(5):608-15. doi: 10.1002/uog.14885. Epub 2016 Apr 17.
Chen J, Xie L, Dai L, Yu L, Liu L, Zhou Y, Wu G, Qin F, Liu H. Right Heart Function of Fetuses and Infants with Large Ventricular Septal Defect: A Longitudinal Case-Control Study. Pediatr Cardiol. 2016 Dec;37(8):1488-1497. doi: 10.1007/s00246-016-1462-z. Epub 2016 Aug 25.
Natarajan S, Szwast A, Tian Z, McCann M, Soffer D, Rychik J. Right ventricular mechanics in the fetus with hypoplastic left heart syndrome. J Am Soc Echocardiogr. 2013 May;26(5):515-20. doi: 10.1016/j.echo.2013.02.001. Epub 2013 Mar 6.
Nawaytou HM, Peyvandi S, Brook MM, Silverman N, Moon-Grady AJ. Right Ventricular Systolic-to-Diastolic Time Index: Hypoplastic Left Heart Fetuses Differ Significantly from Normal Fetuses. J Am Soc Echocardiogr. 2016 Feb;29(2):143-9. doi: 10.1016/j.echo.2015.08.014. Epub 2015 Sep 26.
Chen Y, Lv G, Li B, Wang Z. Cerebral vascular resistance and left ventricular myocardial performance in fetuses with Ebstein's anomaly. Am J Perinatol. 2009 Apr;26(4):253-8. doi: 10.1055/s-0028-1103152. Epub 2008 Nov 20.
Khandoker AH, Al-Angari HM, Marzbanrad F, Kimura Y. Investigating fetal myocardial function in heart anomalies by Doppler myocardial performance indices. Annu Int Conf IEEE Eng Med Biol Soc. 2017 Jul;2017:2197-2200. doi: 10.1109/EMBC.2017.8037290.
Axt-Fliedner R, Graupner O, Kawecki A, Degenhardt J, Herrmann J, Tenzer A, Doelle A, Willruth A, Steinhard J, Gembruch U, Bahlmann F, Enzensberger C; Fetal Cardiac Imaging Research Group, Germany. Evaluation of right ventricular function in fetuses with hypoplastic left heart syndrome using tissue Doppler techniques. Ultrasound Obstet Gynecol. 2015 Jun;45(6):670-7. doi: 10.1002/uog.14736. Epub 2015 May 11.
Graupner O, Enzensberger C, Wieg L, Willruth A, Steinhard J, Gembruch U, Doelle A, Bahlmann F, Kawecki A, Degenhardt J, Wolter A, Herrmann J, Axt-Fliedner R; Fetal Cardiac Imaging Research Group Germany. Evaluation of right ventricular function in fetal hypoplastic left heart syndrome by color tissue Doppler imaging. Ultrasound Obstet Gynecol. 2016 Jun;47(6):732-8. doi: 10.1002/uog.14940.
Pedra SR, Hornberger LK, Leal SM, Taylor GP, Smallhorn JF. Cardiac function assessment in patients with family history of nonhypertrophic cardiomyopathy: a prenatal and postnatal study. Pediatr Cardiol. 2005 Sep-Oct;26(5):543-52. doi: 10.1007/s00246-004-0688-3.
Clur SB, Vink AS, Etheridge SP, Robles de Medina PG, Rydberg A, Ackerman MJ, Wilde AA, Blom NA, Benson DW, Herberg U, Donofrio MT, Cuneo BF. Left Ventricular Isovolumetric Relaxation Time Is Prolonged in Fetal Long-QT Syndrome. Circ Arrhythm Electrophysiol. 2018 Apr;11(4):e005797. doi: 10.1161/CIRCEP.117.005797.
Yozgat Y, Kilic A, Ozdemir R, Karadeniz C, Kucuk M, Karaarslan U, Mese T, Unal N. Modified myocardial performance index is not affected in fetuses with an isolated echogenic focus in the left ventricle. J Matern Fetal Neonatal Med. 2015 Feb;28(3):333-7. doi: 10.3109/14767058.2014.916679. Epub 2014 May 22.
Acharya G, Pavlovic M, Ewing L, Nollmann D, Leshko J, Huhta JC. Comparison between pulsed-wave Doppler- and tissue Doppler-derived Tei indices in fetuses with and without congenital heart disease. Ultrasound Obstet Gynecol. 2008 Apr;31(4):406-11. doi: 10.1002/uog.5292.
Patey O, Carvalho JS, Thilaganathan B. Urgent neonatal balloon atrial septostomy in simple transposition of the great arteries: predictive value of fetal cardiac parameters. Ultrasound Obstet Gynecol. 2021 May;57(5):756-768. doi: 10.1002/uog.22164.
Crispi F, Valenzuela-Alcaraz B, Cruz-Lemini M, Gratacos E. Ultrasound assessment of fetal cardiac function. Australas J Ultrasound Med. 2013 Nov;16(4):158-167. doi: 10.1002/j.2205-0140.2013.tb00242.x. Epub 2015 Dec 31.
Acharya G, Archer N, Huhta JC. Functional assessment of the evolution of congenital heart disease in utero. Curr Opin Pediatr. 2007 Oct;19(5):533-7. doi: 10.1097/MOP.0b013e3282efd2a2.
Maheshwari P, Henry A, Welsh AW. The Fetal Modified Myocardial Performance Index: Is Automation the Future? Biomed Res Int. 2015;2015:215910. doi: 10.1155/2015/215910. Epub 2015 Jun 22.
Herling L, Johnson J, Ferm-Widlund K, Zamprakou A, Westgren M, Acharya G. Automated quantitative evaluation of fetal atrioventricular annular plane systolic excursion. Ultrasound Obstet Gynecol. 2021 Dec;58(6):853-863. doi: 10.1002/uog.23703.
Garcia-Canadilla P, Sanchez-Martinez S, Crispi F, Bijnens B. Machine Learning in Fetal Cardiology: What to Expect. Fetal Diagn Ther. 2020;47(5):363-372. doi: 10.1159/000505021. Epub 2020 Jan 7.
Liu Y, Chen S, Zuhlke L, Black GC, Choy MK, Li N, Keavney BD. Global birth prevalence of congenital heart defects 1970-2017: updated systematic review and meta-analysis of 260 studies. Int J Epidemiol. 2019 Apr 1;48(2):455-463. doi: 10.1093/ije/dyz009.
Cohn JN, Ferrari R, Sharpe N. Cardiac remodeling--concepts and clinical implications: a consensus paper from an international forum on cardiac remodeling. Behalf of an International Forum on Cardiac Remodeling. J Am Coll Cardiol. 2000 Mar 1;35(3):569-82. doi: 10.1016/s0735-1097(99)00630-0.
Tan CMJ, Lewandowski AJ. The Transitional Heart: From Early Embryonic and Fetal Development to Neonatal Life. Fetal Diagn Ther. 2020;47(5):373-386. doi: 10.1159/000501906. Epub 2019 Sep 18.
Peixoto AB, Bravo-Valenzuela NJ, Rocha LA, Araujo Junior E. Spectral Doppler, tissue Doppler, and speckle-tracking echocardiography for the evaluation of fetal cardiac function: an update. Radiol Bras. 2021 Mar-Apr;54(2):99-106. doi: 10.1590/0100-3984.2020.0052.
Donofrio MT, Moon-Grady AJ, Hornberger LK, Copel JA, Sklansky MS, Abuhamad A, Cuneo BF, Huhta JC, Jonas RA, Krishnan A, Lacey S, Lee W, Michelfelder EC Sr, Rempel GR, Silverman NH, Spray TL, Strasburger JF, Tworetzky W, Rychik J; American Heart Association Adults With Congenital Heart Disease Joint Committee of the Council on Cardiovascular Disease in the Young and Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and Council on Cardiovascular and Stroke Nursing. Diagnosis and treatment of fetal cardiac disease: a scientific statement from the American Heart Association. Circulation. 2014 May 27;129(21):2183-242. doi: 10.1161/01.cir.0000437597.44550.5d. Epub 2014 Apr 24. Erratum In: Circulation. 2014 May 27;129(21):e512.
Wieczorek A, Hernandez-Robles J, Ewing L, Leshko J, Luther S, Huhta J. Prediction of outcome of fetal congenital heart disease using a cardiovascular profile score. Ultrasound Obstet Gynecol. 2008 Mar;31(3):284-8. doi: 10.1002/uog.5177.
Huhta JC. Diagnosis and treatment of foetal heart failure: foetal echocardiography and foetal hydrops. Cardiol Young. 2015 Aug;25 Suppl 2:100-6. doi: 10.1017/S104795111500089X.
Public notes

Contacts
Principal investigator
Name 0 0
Anna Erenbourg, MD
Address 0 0
The University of New South Wales
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Anna Erenbourg, MD
Address 0 0
Country 0 0
Phone 0 0
+61423879866
Fax 0 0
Email 0 0
a.erenbourg@unsw.edu.au
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT05698277