Heart Disease
Conditions
Brief summary
Safety and Efficacy Study in pediatric subjects aged 9 to 17 years of age with suboptimal LV EBD on non-contrast 2D echocardiography. Imaging modalities that are used throughout the study in pediatric subjects represented those utilized in routine clinical practice in adults.
Detailed description
This was a Phase III, multicenter, open-label study that was to be conducted at approximately 7-12 sites in the United States, Canada and Europe in pediatric patients with suboptimal LV EBD on non-contrast 2D transthoracic echocardiography. It was estimated that 92 patients were to be enrolled to provide 73 evaluable patients. Three cardiologists unaffiliated with enrolling centers (blinded readers), blinded to the patient's identity and clinical profile were to independently evaluate the echocardiograms. The efficacy analysis was primarily based on the blinded reader evaluations. Imaging modalities that are used throughout the study in pediatric subjects represented those utilized in routine clinical practice in adults. One of the sites participating in this study was to be asked to consent a subset of patients for additional blood sampling for analysis of SF6 concentration in blood from a total of 6 patients (3 males and 3 females) in the age group 9 up to 12 years of age and 6 patients (3 males and 3 females) in the age of \>12 up to and including 17 years. The current study was designed to assess the efficacy of Lumason-enhanced echocardiography in pediatric patients.
Interventions
DRUGsulphur hexafluoride lipid-type A microspheres
Ultrasound imaging contrast agent
Sponsors
Bracco Diagnostics, Inc
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
9 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Provide Written informed consent from parent(s) or legal guardian * Provide assent when required according to local regulations * Suspected of having cardiac disease or undergoing evaluation of cardiac anatomy for congenital heart disease * Undergone a previous transthoracic echocardiogram within one month prior to enrollment resulting in suboptimal left ventricular endocardial border defined as ≥ 2 contiguous segments in any given view that cannot be visualized.
Exclusion criteria
* Children \< 9 years of age * Previously enrolled in the study * Administered any other contrast agent either intravascularly or orally within 48 hours of Lumason administration * Known right-to-left, bidirectional or transient cardiac shunt (ruled out with agitated saline study performed before administration of Lumason) * Known hypersensitivity to one or more of the ingredients of the investigational product * Received an investigational compound within 30 days before enrolling into this study * Pregnant or lactating female * Determined by investigator to be unsuitable for the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Total Left Ventricular Endocardial Border Delineation (LV EBD) Scores | Immediately post dose-Day 1 | The total LV EBD score for a subject was the total of the EBD scores (Inadequate - 0, sufficient - 1, Good - 2) from the 17 segments (from the apical 4-chamber, apical 2-chamber and apical long (3-chamber) views, according to the guidelines of the American Society of Echocardiography). The total LV EBD scores could range from 0 to 34 and are presented below for each of the three readers for both unenhanced ultrasound (UEUS) and contrast-enhanced ultrasound (CEUS). Change from baseline is the difference between UEUS and CEUS in total LV EBD scores. |
| Percentage of Participants With Adequate Left Ventricular Opacification (LVO) | Immediately post dose-Day 1 | LVO was graded as 0 to +3, 4-point rating scale. Left ventricular opacification rating of +2 (non-homogeneous) or +3 (complete and homogeneous) was considered as adequate LVO. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events | Up to 72 hours post dose | To obtain safety data in pediatric subjects administered Lumason for LV EBD improvement during echocardiography |
Countries
United States
Participant flow
Recruitment details
Study Initiation Date (first subject enrolled): 20 October 2015; Study Completion Date (last subject completed study related activities): 20 January 2018. Enrolment was at 2 sites in the US. Even though last subject enrolled was 20 January 2018, FDA release from completion of enrolment was 31 May 2018. Blinded read completion was 13 August 2018.
Pre-assignment details
The study was terminated early due to challenges with enrollment. At the time of termination, 13 subjects were enrolled and 12 subjects were dosed with Lumason, thus the efficacy analysis was considered as exploratory and p-values are not included in the Results section. PK assessment was not performed due to enrollment difficulties.
Participants by arm
| Arm | Count |
|---|---|
| Lumason All patients were administered, Lumason (sulphur hexafluoride lipid-type A microspheres) an ultrasound contrast agent as a single 0.03 mL/kg bolus injection during echocardiography. | 12 |
| Total | 12 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Protocol Violation | 1 |
Baseline characteristics
| Characteristic | Lumason |
|---|---|
| Age, Continuous | 13.8 years STANDARD_DEVIATION 2.29 |
| Age, Customized Age group 10 to 11 years | 0 Participants |
| Age, Customized Age group 12 to 15 years | 8 Participants |
| Age, Customized Age group 16-17 | 3 Participants |
| Age, Customized Age group 6 to 9 years | 1 Participants |
| Body Mass Index | 26.35 kg/m^2 STANDARD_DEVIATION 12.092 |
| Height | 156.1 cm STANDARD_DEVIATION 28.51 |
| Race/Ethnicity, Customized Asian | 0 participants |
| Race/Ethnicity, Customized Black | 2 participants |
| Race/Ethnicity, Customized Other | 0 participants |
| Race/Ethnicity, Customized White | 10 participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 5 Participants |
| Weight | 60.76 kg STANDARD_DEVIATION 23.846 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 12 |
| other Total, other adverse events | 5 / 12 |
| serious Total, serious adverse events | 0 / 12 |
Outcome results
Primary
Change From Baseline in Total Left Ventricular Endocardial Border Delineation (LV EBD) Scores
The total LV EBD score for a subject was the total of the EBD scores (Inadequate - 0, sufficient - 1, Good - 2) from the 17 segments (from the apical 4-chamber, apical 2-chamber and apical long (3-chamber) views, according to the guidelines of the American Society of Echocardiography). The total LV EBD scores could range from 0 to 34 and are presented below for each of the three readers for both unenhanced ultrasound (UEUS) and contrast-enhanced ultrasound (CEUS). Change from baseline is the difference between UEUS and CEUS in total LV EBD scores.
Time frame: Immediately post dose-Day 1
Population: All subjects who received IP and had data available for both unenhanced ultrasound (UEUS) and contrast-enhanced ultrasound (CEUS) were included in ITD population.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Off-site Reader 1 UEUS | Change From Baseline in Total Left Ventricular Endocardial Border Delineation (LV EBD) Scores | 6.4 score on a scale |
| Off-site Reader 1 CEUS | Change From Baseline in Total Left Ventricular Endocardial Border Delineation (LV EBD) Scores | 33.5 score on a scale |
| Off-site Reader 2 UEUS | Change From Baseline in Total Left Ventricular Endocardial Border Delineation (LV EBD) Scores | 10.6 score on a scale |
| Off-site Reader 2 CEUS | Change From Baseline in Total Left Ventricular Endocardial Border Delineation (LV EBD) Scores | 33.3 score on a scale |
| Off-site Reader 3 UEUS | Change From Baseline in Total Left Ventricular Endocardial Border Delineation (LV EBD) Scores | 7.3 score on a scale |
| Off-site Reader 3 CEUS | Change From Baseline in Total Left Ventricular Endocardial Border Delineation (LV EBD) Scores | 33.0 score on a scale |
Primary
Percentage of Participants With Adequate Left Ventricular Opacification (LVO)
LVO was graded as 0 to +3, 4-point rating scale. Left ventricular opacification rating of +2 (non-homogeneous) or +3 (complete and homogeneous) was considered as adequate LVO.
Time frame: Immediately post dose-Day 1
Population: All subjects who received IP and had data available for contrast-enhanced ultrasound (CEUS) were included in ITD population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Off-site Reader 1 UEUS | Percentage of Participants With Adequate Left Ventricular Opacification (LVO) | 100 percentage of participants |
| Off-site Reader 1 CEUS | Percentage of Participants With Adequate Left Ventricular Opacification (LVO) | 100 percentage of participants |
| Off-site Reader 2 UEUS | Percentage of Participants With Adequate Left Ventricular Opacification (LVO) | 100 percentage of participants |
Secondary
Number of Participants With Adverse Events
To obtain safety data in pediatric subjects administered Lumason for LV EBD improvement during echocardiography
Time frame: Up to 72 hours post dose
Population: Summary of adverse events in the safety population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Off-site Reader 1 UEUS | Number of Participants With Adverse Events | Number of Subjects With at Least 1 AE | 5 Participants |
| Off-site Reader 1 UEUS | Number of Participants With Adverse Events | Number of Subjects With AEs by Intensity - Mild | 4 Participants |
| Off-site Reader 1 UEUS | Number of Participants With Adverse Events | Number of Subjects With AEs by Intensity -Moderate | 1 Participants |
| Off-site Reader 1 UEUS | Number of Participants With Adverse Events | Number of Subjects With AEs by Intensity -Severe | 0 Participants |