Evaluation of Safety and Efficacy of Lumason in Pediatric Echocardiography
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 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. |
Drug: sulphur hexafluoride lipid-type A microspheres
Ultrasound imaging contrast agent
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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
Eligibility Criteria
Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Washington University School of Medicine in Saint Louis | Saint Louis | Missouri | United States | 63110 |
| 2 | University of Nebraska | Omaha | Nebraska | United States | 68114 |
Sponsors and Collaborators
- Bracco Diagnostics, Inc
Investigators
- Study Director: Melda Dolan, M.D., Bracco Diagnostics, Inc
Study Documents (Full-Text)
More Information
Publications
None provided.- BR1-140
Study Results
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 Detail | 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. |
| Arm/Group Title | Lumason |
|---|---|
| Arm/Group Description | 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. |
| Period Title: Overall Study | |
| STARTED | 13 |
| COMPLETED | 12 |
| NOT COMPLETED | 1 |
Baseline Characteristics
| Arm/Group Title | Lumason |
|---|---|
| Arm/Group Description | 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. |
| Overall Participants | 12 |
| Age (years) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [years] |
13.8
(2.29)
|
| Age, Customized (Count of Participants) | |
| 6 to 9 years |
1
8.3%
|
| 10 to 11 years |
0
0%
|
| 12 to 15 years |
8
66.7%
|
| 16-17 |
3
25%
|
| Sex: Female, Male (Count of Participants) | |
| Female |
7
58.3%
|
| Male |
5
41.7%
|
| Race/Ethnicity, Customized (participants) [Number] | |
| White |
10
83.3%
|
| Black |
2
16.7%
|
| Asian |
0
0%
|
| Other |
0
0%
|
| Height (cm) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [cm] |
156.1
(28.51)
|
| Weight (kg) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [kg] |
60.76
(23.846)
|
| Body Mass Index (kg/m^2) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [kg/m^2] |
26.35
(12.092)
|
Outcome Measures
| Title | Change From Baseline in Total Left Ventricular Endocardial Border Delineation (LV EBD) Scores |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Off-site Reader 1 UEUS | Off-site Reader 1 CEUS | Off-site Reader 2 UEUS | Off-site Reader 2 CEUS | Off-site Reader 3 UEUS | Off-site Reader 3 CEUS |
|---|---|---|---|---|---|---|
| Arm/Group Description | Off-site Reader 1 UEUS Assessment | Off-site Reader 1 CEUS Assessment | Off-site Reader 2 UEUS Assessment | Off-site Reader 2 CEUS Assessment | Off-site Reader 3 UEUS Assessment | Off-site Reader 3 CEUS Assessment |
| Measure Participants | 12 | 12 | 12 | 12 | 12 | 12 |
| Mean (95% Confidence Interval) [score on a scale] |
6.4
|
33.5
|
10.6
|
33.3
|
7.3
|
33.0
|
| Title | Percentage of Participants With Adequate Left Ventricular Opacification (LVO) |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All subjects who received IP and had data available for contrast-enhanced ultrasound (CEUS) were included in ITD population. |
| Arm/Group Title | Off-site Reader 1 CEUS | Off-site Reader 2 CEUS | Off-site Reader 3 CEUS |
|---|---|---|---|
| Arm/Group Description | Off-site Reader 1 CEUS | Off-site Reader 2 CEUS | Off-site Reader 3 CEUS |
| Measure Participants | 12 | 12 | 12 |
| Number (95% Confidence Interval) [percentage of participants] |
100
833.3%
|
100
NaN
|
100
NaN
|
| Title | Number of Participants With Adverse Events |
|---|---|
| Description | To obtain safety data in pediatric subjects administered Lumason for LV EBD improvement during echocardiography |
| Time Frame | Up to 72 hours post dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| Summary of adverse events in the safety population |
| Arm/Group Title | Lumason |
|---|---|
| Arm/Group Description | 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 |
| Measure Participants | 12 |
| Number of Subjects With at Least 1 AE |
5
41.7%
|
| Number of Subjects With AEs by Intensity - Mild |
4
33.3%
|
| Number of Subjects With AEs by Intensity -Moderate |
1
8.3%
|
| Number of Subjects With AEs by Intensity -Severe |
0
0%
|
Adverse Events
| Time Frame | Subjects were monitored for any untoward medical events from the time of signed Informed Consent through 72 hours after IP administration. | |
|---|---|---|
| Adverse Event Reporting Description | ||
| Arm/Group Title | Lumason | |
| Arm/Group Description | 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. | |
All Cause Mortality |
||
| Lumason | ||
| Affected / at Risk (%) | # Events | |
| Total | 0/12 (0%) | |
Serious Adverse Events |
||
| Lumason | ||
| Affected / at Risk (%) | # Events | |
| Total | 0/12 (0%) | |
Other (Not Including Serious) Adverse Events |
||
| Lumason | ||
| Affected / at Risk (%) | # Events | |
| Total | 5/12 (41.7%) | |
| Gastrointestinal disorders | ||
| Vomiting | 1/12 (8.3%) | 1 |
| General disorders | ||
| Injection site bruising | 1/12 (8.3%) | 1 |
| Pyrexia | 1/12 (8.3%) | 1 |
| Nervous system disorders | ||
| Headache | 1/12 (8.3%) | 1 |
| Psychiatric disorders | ||
| Abnormal behavior | 1/12 (8.3%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||
| Haemoptysis | 1/12 (8.3%) | 1 |
| Skin and subcutaneous tissue disorders | ||
| Rash | 1/12 (8.3%) | 1 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Melda S. Dolan, MD, FACC, FASE, Head, Medical Affairs and Cardiac Ultrasound Programs |
|---|---|
| Organization | Bracco Diagnostics Inc. |
| Phone | 1-609-514-2506 |
| Melda.Dolan@diag.bracco.com |
- BR1-140