Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12619000529145
Ethics application status
Not required
Date submitted
27/03/2019
Date registered
3/04/2019
Date last updated
3/04/2019
Date data sharing statement initially provided
3/04/2019
Date results information initially provided
3/04/2019
Type of registration
Retrospectively registered

Titles & IDs
Public title
Three-dimensional speckle-tracking echocardiography as a tool to predict subclinical left ventricular dysfunction before percutaneous closure of a patent ductus arteriosus.
Scientific title
Three-dimensional speckle-tracking echocardiography as a tool to predict subclinical left ventricular dysfunction before percutaneous closure of a patent ductus arteriosus.
Secondary ID [1] 297419 0
Nil known
Universal Trial Number (UTN)
Trial acronym
UPDATE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
patent ductus arteriosus 311594 0
Condition category
Condition code
Cardiovascular 310221 310221 0 0
Diseases of the vasculature and circulation including the lymphatic system

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
Early detection of left ventricular dysfunction in patients diagnosed with hemodynamic significant PDA: application of Three-dimensional speckle-tracking echocardiography versus conventional echocardiography. Comparison of study parameters beteen PDA patients (n=13) and control patients with normal echocardiograms (n=27)

Percutaneous closure of the ductus arteriosus: The procedure was performed under general anesthesia, systemic heparinization, anti-microbial prophylaxis, with at least an arterial approach (femoral artery) and often a venous approach when a Duct Occluder prosthesis was implanted. An angiography of the descending aorta allows accurate sizing of the PDA as well as a shape description helping device selection for closure. Pulmonary artery pressure was measured. Once the position was found adequate, repeated angiograms were performed, before and after the release of the device.

Conventional echocardiographic parameters
In PDA patients, primary echocardiogram was performed 24 hours before cardiac catheterization followed by a second ultrasound heart scan 24 hours after the procedure. In control patients, a complete echocardiogram was carried out at the Outpatient Cardiac Clinic including conventional methods, as well as 3D speckle tracking measurements during the course of one visit.
A Philips ultrasound system (Philips IE33) with pS8, S5 or X5 probes was used according to age and weight. Echocardiographic measurements included: LVEDD (left ventricular end-diastolic diameter), LVESD (left ventricular end-systolic diameter), EF (ejection fraction), FS (fractional shortening), LVOT VTI (left ventricular outflow velocity time integral), E early diastolic transmitral flow velocity, A late diastolic transmitral flow velocity, Ea early diastolic mitral annular tissue velocity.

Three-Dimensional speckle tracking echocardiography (3D strain):
Three D video loop was performed in apical 4-chambers view with the acquisition of 4 consecutive cardiac cycles subsequently digitally stored for offline analysis. Then, the best acquisition was selected and post-treated offline, by a single sonographer. The frame rate was > 50Hz. The analysis was performed using a dedicated quantification software (4D LV-3.0 Analysis, TomTec Imaging Systems, Unterschleissheim, Germany). The measurements were made using the dataset with the best choice in terms of image quality. The 3D acquisition makes it possible to obtain 3 apical views: 4 cavities, 3 cavities and 2 cavities as well as a small axis orthogonal to the first 3 views. Adjustment of the aortic valve, mitral and apex position was made. Then, the surface of the 3D endocardium was automatically reconstructed and followed in a 3D space during the cardiac cycle. The endocardial surface was manually adjusted when needed until a better match was obtained with the actual position of the endocardium visualized in the different points of view. Subsequently, the software displays a 3D model of static left ventricle automatically calculated by the application. Finally, the left ventricle was automatically divided into sixteen 3-D segments using the standard segmentation of the American Society of Echocardiography. The curves and maps of the global (circumferential and longitudinal) strain and the analysis of all LV 3D strain segments (circumferential mean, radial and longitudinal strain) were calculated.
The following global analysis parameters retrieved from 4D LV-analysis software were evaluated:
- EDV (ml): end-diastolic volume, (maximum volume of the time curve minus overall volume)
- ESV (ml): end-systolic volume (minimum volume of the time curve minus overall volume)
- SV (ml): systolic flow (EDV minus ESV)
- EF (%): ejection fraction ((SV / EDV) x 100)
- GLS (%): global longitudinal deformation (global shortening of the longitudes of the surface model)
- GCS (%): global circumferential deformation (global shortening of the latitudes of the surface model)
- Longitudinal strand, GLS mean segmental (%): the longitudinal strain values of all segments are summed to calculate their average
- Circumferential strain, GCS mean segmental (%): the circumferential deformation values of all segments are summed to calculate their mean
- Radial strain, GRS average segmental (%): Radial deformation values of all segments are summed to calculate their average
- Torsion: the LV twist defined as the angle of rotation of the apex with respect to the base
Negative deformation values reflect a shortening, whereas uniquely positive values represent elongation or thickening.
Intervention code [1] 313674 0
Early Detection / Screening
Comparator / control treatment
healthy children with normal heart
Control group
Active

Outcomes
Primary outcome [1] 319574 0
Composite primary outcome:
Global, longitudinal, radial and circumferential 3D-strain in both study groups (PDA cases and control patients)
Timepoint [1] 319574 0
For PDA patients: Before cardiac catherization for PDA closure and at Day one post PDA closure
For control patients: during complete echocardiogram carried out at the Outpatient Cardiac Clinic
Primary outcome [2] 319627 0
Composite outcome: Conventional echocardiogram measurements in both study groups (PDA cases and control patients).
Echocardiogram measurements were as follows: LVEDD (left ventricular end-diastolic diameter), LVESD (left ventricular end-systolic diameter), EF (ejection fraction), FS (fractional shortening), LVOT VTI (left ventricular outflow velocity time integral), E early diastolic transmitral flow velocity, A late diastolic transmitral flow velocity, Ea early diastolic mitral annular tissue velocity.
Timepoint [2] 319627 0
For PDA patients: Before cardiac catherization for PDA closure and at Day one post PDA closure
For control patients: during complete echocardiogram carried out at the Outpatient Cardiac Clinic
Secondary outcome [1] 368756 0
Three-dimensional 3D Strain measurements (global, longitudinal, radial and circumferential) in control subjects, according to age
(This outcome differs from the first primary outcome because it is described, according to age, in control patients only)
Timepoint [1] 368756 0
During complete echocardiogram carried out at the Outpatient Cardiac Clinic

Eligibility
Key inclusion criteria
Inclusion criteria for PDA patients:
- patients seen at the French West Indies Center for Congenital Heart Diseases (University Hospital of Martinique) from January 2017 to March 2018
_ aged from 0 to 18 years
- weighing over 3 kg
- presenting with a minimal PDA diameter of more than 2 mm, exclusive left to right shunt
- presenting with LV volume overload

Inclusion criteria for control patients:
- patients seen at the Outpatient Cardiac Clinic (University Hospital of Martinique) from January 2017 to March 2018
_ aged from 0 to 18 years
- weighing over 3 kg
- consulting for variable reasons, such as cardiac murmur, chest pain or palpitations
- normal echocardiogram (echocardiogram including conventional methods and 3D speckleel tracking measurements)
Minimum age
0 Years
Maximum age
19 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria for PDA patients:
- presenting with other heart defects or with a contra indication to cardiac catheterization

Exclusion criteria for control patients:
none

Study design
Purpose
Screening
Duration
Cross-sectional
Selection
Defined population
Timing
Retrospective
Statistical methods / analysis
A complete descriptive analysis was performed using SAS software 9.4 for Windows (SAS Institute, Cary North Carolina, USA).
Normal distribution of the data was first verified by the Shapiro-Wilk test. Mean and standard deviation were reported for continuous normally distributed data while median and min-max ranges were described for non-normally distributed data. Categorical variables were presented as frequencies or percentages.
The following tests were used for group comparisons when appropriate: Student t-tests or Wilcoxon-Mann-Whitney-Kruskall-Wallis tests for continuous variables. Correlation between variables was also evaluated. All inferential analyses were performed by means of a 2-sided test, with the level of statistical significance set at p<0.05.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
1/01/2017
Date of last participant enrolment
Anticipated
Actual
31/03/2018
Date of last data collection
Anticipated
Actual
6/04/2018
Sample size
Target
50
Accrual to date
Final
40
Recruitment outside Australia
Country [1] 21284 0
Martinique
State/province [1] 21284 0

Funding & Sponsors
Funding source category [1] 301987 0
Hospital
Name [1] 301987 0
University Hospital of Martinique
Country [1] 301987 0
Martinique
Primary sponsor type
Hospital
Name
University Hospital of Martinique
Address
CHU de Martinique (University Hospital of Martinique)
Pierre Zobda Quitman Hospital - CS 90 632
97261 Fort-de-France Cedex
Country
Martinique
Secondary sponsor category [1] 301768 0
None
Name [1] 301768 0
Not applicable
Address [1] 301768 0
Not applicable
Country [1] 301768 0

Ethics approval
Ethics application status
Not required

Summary
Brief summary
Patent Ductus Arteriosus (PDA) is one of the most common congenital heart defects, which can be diagnosed at any age of life. The hemodynamic impact of PDA depends mainly on the amount of shunting.

Ths study hypothesis is that 3D strain measurements are significantly decreased before closure of moderate to large PDA in patients who present with normal left ventricular systolic function, as measured by conventional echocardiographic parameters.

The aim of this study was to evaluate, in comparison to conventional echocardiographic parameters, the value of 3D-Strain in the early detection of left ventricular dysfunction before percutaneous closure of PDA.
Trial website
Trial related presentations / publications
Public notes
The present study is based on the retrospective analysis of anonymized data, collected in agreement with the University Hospital of Martinique’s ethics policy. This study was conducted in accordance with the Declaration of Helsinki.
Furthermore, on the basis of the study’s purely observational design (not modifying conventional medical practice and procedures) and data collection process, written informed consent form was not required for 3D speckle tracking according to French law, as the studies were part of the regular management of the children using repeated echocardiograms (informed consent for cardiac catheterization was systematically collected on patient admission).
As such, study participants or their legal representatives, received information regarding study protocol and objectives. Informed verbal consent was then obtained from legal representatives or patients. Once verbal informed consent obtained, it was documented in the study participant’s medical file.

Contacts
Principal investigator
Name 90990 0
Dr BRARD Melanie
Address 90990 0
Department of Cardiology
CHU de Martinique (University Hospital of Martinique)
Pierre Zobda Quitman Hospital - CS 90 632
97261 Fort-de-France Cedex
Country 90990 0
Martinique
Phone 90990 0
+596 696 23 28 63
Fax 90990 0
Email 90990 0
[email protected]
Contact person for public queries
Name 90991 0
Dr BRARD Melanie
Address 90991 0
Department of Cardiology
CHU de Martinique (University Hospital of Martinique)
Pierre Zobda Quitman Hospital - CS 90 632
97261 Fort-de-France Cedex
Country 90991 0
Martinique
Phone 90991 0
+596 696 23 28 63
Fax 90991 0
Email 90991 0
[email protected]
Contact person for scientific queries
Name 90992 0
Dr BRARD Melanie
Address 90992 0
Department of Cardiology
CHU de Martinique (University Hospital of Martinique)
Pierre Zobda Quitman Hospital - CS 90 632
97261 Fort-de-France Cedex
Country 90992 0
Martinique
Phone 90992 0
+596 696 23 28 63
Fax 90992 0
Email 90992 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.