Trial Outcomes & Findings for An Efficacy and Safety Study of Sonazoid™ and SonoVue® in Participants With Focal Liver Lesions, Undergoing Pre- and Post-Contrast Ultrasound Imaging (NCT NCT03335566)
NCT ID: NCT03335566
Last Updated: 2018-10-31
Results Overview
Accuracy improvement was calculated by the number of participants with improved diagnoses from the pre-contrast diagnosis to the post-contrast diagnosis divided by the total number of participants, multiplied by 100. Assessments were done by 3 blinded readers. Efficacy population which included all participants who received Sonazoid™ or SonoVue®, for whom pre-contrast \& post-contrast images were recorded, \& for whom there was a reference standard contrast-enhanced computed tomography (CECT)/contrast-enhanced magnetic resonance imaging (CE-MRI) examination or biopsy.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
424 participants
Primary outcome timeframe
Pre-administration up to 15 minutes post-administration
Results posted on
2018-10-31
Participant Flow
The study was conducted at 17 centres in China, Korea and Taiwan. A total of 424 participants were enrolled between 11 May 2014 and 9 April 2015.
Participants were randomised in 1:1 ratio to receive either Sonazoid™ or SonoVue®.
Participant milestones
| Measure |
Sonazoid™
Participants received single intravenous (I.V) bolus injection of Sonazoid™ 0.12 microliter (µL) microbubbles (MB)/kilogram (kg) body weight.
|
SonoVue®
Participants received single I.V bolus injection of SonoVue® 2.4 milliliter (mL).
|
|---|---|---|
|
Overall Study
STARTED
|
218
|
206
|
|
Overall Study
COMPLETED
|
214
|
203
|
|
Overall Study
NOT COMPLETED
|
4
|
3
|
Reasons for withdrawal
| Measure |
Sonazoid™
Participants received single intravenous (I.V) bolus injection of Sonazoid™ 0.12 microliter (µL) microbubbles (MB)/kilogram (kg) body weight.
|
SonoVue®
Participants received single I.V bolus injection of SonoVue® 2.4 milliliter (mL).
|
|---|---|---|
|
Overall Study
Adverse Event
|
0
|
1
|
|
Overall Study
Lost to Follow-up
|
1
|
0
|
|
Overall Study
Technical Problems
|
1
|
0
|
|
Overall Study
Protocol Violation
|
1
|
0
|
|
Overall Study
Other than specified above
|
1
|
2
|
Baseline Characteristics
An Efficacy and Safety Study of Sonazoid™ and SonoVue® in Participants With Focal Liver Lesions, Undergoing Pre- and Post-Contrast Ultrasound Imaging
Baseline characteristics by cohort
| Measure |
Sonazoid™
n=218 Participants
Participants received single intravenous (I.V) bolus injection of Sonazoid™ 0.12 microliter (µL) microbubbles (MB)/kilogram (kg) body weight.
|
SonoVue®
n=206 Participants
Participants received single I.V bolus injection of SonoVue® 2.4 milliliter (mL).
|
Total
n=424 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
54.5 years
STANDARD_DEVIATION 12.61 • n=5 Participants
|
52.2 years
STANDARD_DEVIATION 13.77 • n=7 Participants
|
53.4 years
STANDARD_DEVIATION 13.22 • n=5 Participants
|
|
Sex: Female, Male
Female
|
81 Participants
n=5 Participants
|
81 Participants
n=7 Participants
|
162 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
137 Participants
n=5 Participants
|
125 Participants
n=7 Participants
|
262 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
218 Participants
n=5 Participants
|
206 Participants
n=7 Participants
|
424 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Pre-administration up to 15 minutes post-administrationPopulation: Analysis was performed on efficacy population. Here, number analysed=participants with available data for specified category.
Accuracy improvement was calculated by the number of participants with improved diagnoses from the pre-contrast diagnosis to the post-contrast diagnosis divided by the total number of participants, multiplied by 100. Assessments were done by 3 blinded readers. Efficacy population which included all participants who received Sonazoid™ or SonoVue®, for whom pre-contrast \& post-contrast images were recorded, \& for whom there was a reference standard contrast-enhanced computed tomography (CECT)/contrast-enhanced magnetic resonance imaging (CE-MRI) examination or biopsy.
Outcome measures
| Measure |
Sonazoid™
n=169 Participants
Participants received single I.V bolus injection of Sonazoid™ 0.12 µL MB/kg body weight.
|
SonoVue®
n=169 Participants
Participants received single I.V bolus injection of SonoVue® 2.4 mL.
|
|---|---|---|
|
Percentage of Participants With Accuracy Improvement in Post-Contrast Versus Pre-Contrast Ultrasound (US) Examination for Diagnosis of the Target Lesion as Malignant or Benign Against the Reference Diagnosis (RD)/Standard of Truth
Reader 1
|
18.1 percentage of participants
|
24.2 percentage of participants
|
|
Percentage of Participants With Accuracy Improvement in Post-Contrast Versus Pre-Contrast Ultrasound (US) Examination for Diagnosis of the Target Lesion as Malignant or Benign Against the Reference Diagnosis (RD)/Standard of Truth
Reader 2
|
22.1 percentage of participants
|
14.6 percentage of participants
|
|
Percentage of Participants With Accuracy Improvement in Post-Contrast Versus Pre-Contrast Ultrasound (US) Examination for Diagnosis of the Target Lesion as Malignant or Benign Against the Reference Diagnosis (RD)/Standard of Truth
Reader 3
|
17.0 percentage of participants
|
16.7 percentage of participants
|
SECONDARY outcome
Timeframe: Pre-administration up to 15 minutes post-administrationPopulation: Analysis was performed on efficacy population. Here, number analysed=participants with available data for specified category.
For the cases that can be assessed by the blinded readers both pre- and post-contrast, differences were calculated between the Sonazoid™ and SonoVue® groups in the number of lesions detected during whole-liver imaging (post-contrast minus pre-contrast). The differences were also calculated between the Sonazoid™ and SonoVue® groups in the number of lesions (post-contrast minus reference diagnosis) detected during whole-liver imaging.
Outcome measures
| Measure |
Sonazoid™
n=169 Participants
Participants received single I.V bolus injection of Sonazoid™ 0.12 µL MB/kg body weight.
|
SonoVue®
n=169 Participants
Participants received single I.V bolus injection of SonoVue® 2.4 mL.
|
|---|---|---|
|
Number of Lesions Detected by Post-Contrast US Relative to Number of Lesions Detected by Pre-Contrast US (Both by Blinded Readers[BR]) and Number of Lesions Detected by Post-Contrast US (by BR) Relative to Number of Lesions Detected by RD (Investigators)
Post-contrast minus Pre-contrast: Reader 1
|
0.0 Lesions
Interval -1.0 to 1.0
|
0.0 Lesions
Interval -1.0 to 0.0
|
|
Number of Lesions Detected by Post-Contrast US Relative to Number of Lesions Detected by Pre-Contrast US (Both by Blinded Readers[BR]) and Number of Lesions Detected by Post-Contrast US (by BR) Relative to Number of Lesions Detected by RD (Investigators)
Post-contrast minus Pre-contrast: Reader 2
|
0.0 Lesions
Interval -2.0 to 0.0
|
-1.0 Lesions
Interval -2.0 to 0.0
|
|
Number of Lesions Detected by Post-Contrast US Relative to Number of Lesions Detected by Pre-Contrast US (Both by Blinded Readers[BR]) and Number of Lesions Detected by Post-Contrast US (by BR) Relative to Number of Lesions Detected by RD (Investigators)
Post-contrast minus Pre-contrast: Reader 3
|
0.0 Lesions
Interval -1.0 to 0.0
|
-1.0 Lesions
Interval -2.0 to 0.0
|
|
Number of Lesions Detected by Post-Contrast US Relative to Number of Lesions Detected by Pre-Contrast US (Both by Blinded Readers[BR]) and Number of Lesions Detected by Post-Contrast US (by BR) Relative to Number of Lesions Detected by RD (Investigators)
Post-contrast minus Reference: Reader 1
|
1.0 Lesions
Interval 0.0 to 2.0
|
1.0 Lesions
Interval 0.0 to 1.0
|
|
Number of Lesions Detected by Post-Contrast US Relative to Number of Lesions Detected by Pre-Contrast US (Both by Blinded Readers[BR]) and Number of Lesions Detected by Post-Contrast US (by BR) Relative to Number of Lesions Detected by RD (Investigators)
Post-contrast minus Reference: Reader 2
|
0.0 Lesions
Interval 0.0 to 1.0
|
0.0 Lesions
Interval 0.0 to 0.0
|
|
Number of Lesions Detected by Post-Contrast US Relative to Number of Lesions Detected by Pre-Contrast US (Both by Blinded Readers[BR]) and Number of Lesions Detected by Post-Contrast US (by BR) Relative to Number of Lesions Detected by RD (Investigators)
Post-contrast minus Reference: Reader 3
|
0.0 Lesions
Interval 0.0 to 1.0
|
0.0 Lesions
Interval -1.0 to 1.0
|
SECONDARY outcome
Timeframe: Pre-administration up to 15 minutes post-administrationPopulation: Analysis was performed on efficacy population. Here, number analysed=participants with available data for specified category.
Confidence in diagnoses from the pre- and post-contrast ultrasound examinations was evaluated based on 4-point scale: 0-Unknown (cannot make a judgement on level of confidence), 1- Not confident (another examination was required), 2- Probable (Would have more confidence if another diagnostic imaging test such as MRI or CT was performed), 3- Definite (Sufficient confidence to the extent that another diagnostic imaging test such as MRI or CT was unnecessary).
Outcome measures
| Measure |
Sonazoid™
n=169 Participants
Participants received single I.V bolus injection of Sonazoid™ 0.12 µL MB/kg body weight.
|
SonoVue®
n=169 Participants
Participants received single I.V bolus injection of SonoVue® 2.4 mL.
|
|---|---|---|
|
Number of Participants With Diagnostic Confidence (Evaluated by Blinded Readers) in Pre-Contrast and Post-Contrast Ultrasound Examination Results
Reader 2: Pre-contrast · Unknown (0 points)
|
0 Participants
|
0 Participants
|
|
Number of Participants With Diagnostic Confidence (Evaluated by Blinded Readers) in Pre-Contrast and Post-Contrast Ultrasound Examination Results
Reader 1: Pre-contrast · Definite (3 points)
|
10 Participants
|
11 Participants
|
|
Number of Participants With Diagnostic Confidence (Evaluated by Blinded Readers) in Pre-Contrast and Post-Contrast Ultrasound Examination Results
Reader 1: Pre-contrast · Probable (2 points)
|
113 Participants
|
122 Participants
|
|
Number of Participants With Diagnostic Confidence (Evaluated by Blinded Readers) in Pre-Contrast and Post-Contrast Ultrasound Examination Results
Reader 1: Pre-contrast · Not confident (1 point)
|
46 Participants
|
36 Participants
|
|
Number of Participants With Diagnostic Confidence (Evaluated by Blinded Readers) in Pre-Contrast and Post-Contrast Ultrasound Examination Results
Reader 1: Pre-contrast · Unknown (0 points)
|
0 Participants
|
0 Participants
|
|
Number of Participants With Diagnostic Confidence (Evaluated by Blinded Readers) in Pre-Contrast and Post-Contrast Ultrasound Examination Results
Reader 1: Post Contrast · Definite (3 points)
|
57 Participants
|
54 Participants
|
|
Number of Participants With Diagnostic Confidence (Evaluated by Blinded Readers) in Pre-Contrast and Post-Contrast Ultrasound Examination Results
Reader 1: Post Contrast · Probable (2 points)
|
86 Participants
|
88 Participants
|
|
Number of Participants With Diagnostic Confidence (Evaluated by Blinded Readers) in Pre-Contrast and Post-Contrast Ultrasound Examination Results
Reader 1: Post Contrast · Not confident (1 point)
|
17 Participants
|
15 Participants
|
|
Number of Participants With Diagnostic Confidence (Evaluated by Blinded Readers) in Pre-Contrast and Post-Contrast Ultrasound Examination Results
Reader 1: Post Contrast · Unknown (0 points)
|
0 Participants
|
0 Participants
|
|
Number of Participants With Diagnostic Confidence (Evaluated by Blinded Readers) in Pre-Contrast and Post-Contrast Ultrasound Examination Results
Reader 2: Pre-contrast · Definite (3 points)
|
15 Participants
|
12 Participants
|
|
Number of Participants With Diagnostic Confidence (Evaluated by Blinded Readers) in Pre-Contrast and Post-Contrast Ultrasound Examination Results
Reader 2: Pre-contrast · Probable (2 points)
|
89 Participants
|
79 Participants
|
|
Number of Participants With Diagnostic Confidence (Evaluated by Blinded Readers) in Pre-Contrast and Post-Contrast Ultrasound Examination Results
Reader 2: Pre-contrast · Not confident (1 point)
|
65 Participants
|
78 Participants
|
|
Number of Participants With Diagnostic Confidence (Evaluated by Blinded Readers) in Pre-Contrast and Post-Contrast Ultrasound Examination Results
Reader 2: Post-contrast · Definite (3 points)
|
116 Participants
|
103 Participants
|
|
Number of Participants With Diagnostic Confidence (Evaluated by Blinded Readers) in Pre-Contrast and Post-Contrast Ultrasound Examination Results
Reader 2: Post-contrast · Probable (2 points)
|
43 Participants
|
51 Participants
|
|
Number of Participants With Diagnostic Confidence (Evaluated by Blinded Readers) in Pre-Contrast and Post-Contrast Ultrasound Examination Results
Reader 2: Post-contrast · Not confident (1 point)
|
4 Participants
|
4 Participants
|
|
Number of Participants With Diagnostic Confidence (Evaluated by Blinded Readers) in Pre-Contrast and Post-Contrast Ultrasound Examination Results
Reader 2: Post-contrast · Unknown (0 points)
|
0 Participants
|
0 Participants
|
|
Number of Participants With Diagnostic Confidence (Evaluated by Blinded Readers) in Pre-Contrast and Post-Contrast Ultrasound Examination Results
Reader 3: Pre-contrast · Definite (3 points)
|
38 Participants
|
36 Participants
|
|
Number of Participants With Diagnostic Confidence (Evaluated by Blinded Readers) in Pre-Contrast and Post-Contrast Ultrasound Examination Results
Reader 3: Pre-contrast · Probable (2 points)
|
89 Participants
|
90 Participants
|
|
Number of Participants With Diagnostic Confidence (Evaluated by Blinded Readers) in Pre-Contrast and Post-Contrast Ultrasound Examination Results
Reader 3: Pre-contrast · Not confident (1 point)
|
42 Participants
|
42 Participants
|
|
Number of Participants With Diagnostic Confidence (Evaluated by Blinded Readers) in Pre-Contrast and Post-Contrast Ultrasound Examination Results
Reader 3: Pre-contrast · Unknown (0 points)
|
0 Participants
|
1 Participants
|
|
Number of Participants With Diagnostic Confidence (Evaluated by Blinded Readers) in Pre-Contrast and Post-Contrast Ultrasound Examination Results
Reader 3: Post-contrast · Definite (3 points)
|
130 Participants
|
117 Participants
|
|
Number of Participants With Diagnostic Confidence (Evaluated by Blinded Readers) in Pre-Contrast and Post-Contrast Ultrasound Examination Results
Reader 3: Post-contrast · Probable (2 points)
|
31 Participants
|
36 Participants
|
|
Number of Participants With Diagnostic Confidence (Evaluated by Blinded Readers) in Pre-Contrast and Post-Contrast Ultrasound Examination Results
Reader 3: Post-contrast · Not confident (1 point)
|
4 Participants
|
9 Participants
|
|
Number of Participants With Diagnostic Confidence (Evaluated by Blinded Readers) in Pre-Contrast and Post-Contrast Ultrasound Examination Results
Reader 3: Post-contrast · Unknown (0 points)
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Pre-administration up to 15 minutes post-administrationPopulation: Analysis was performed on efficacy population. Here, number analysed=participants with available data for specified category.
The accuracy improvement was calculated by the number of participants with improved diagnoses from the pre-contrast diagnosis to the post-contrast diagnosis divided by the total number of participants, multiplied by 100. Assessment was performed by 3 blinded readers.
Outcome measures
| Measure |
Sonazoid™
n=169 Participants
Participants received single I.V bolus injection of Sonazoid™ 0.12 µL MB/kg body weight.
|
SonoVue®
n=169 Participants
Participants received single I.V bolus injection of SonoVue® 2.4 mL.
|
|---|---|---|
|
Percentage of Participants With Accuracy Improvement in Post-contrast Versus Pre-contrast Ultrasound Examination for Lesion-Specific Diagnoses of the Target Lesion Against the Reference Diagnosis/Standard of Truth
Reader 1
|
11.9 percentage of participants
|
21.7 percentage of participants
|
|
Percentage of Participants With Accuracy Improvement in Post-contrast Versus Pre-contrast Ultrasound Examination for Lesion-Specific Diagnoses of the Target Lesion Against the Reference Diagnosis/Standard of Truth
Reader 2
|
16.6 percentage of participants
|
15.2 percentage of participants
|
|
Percentage of Participants With Accuracy Improvement in Post-contrast Versus Pre-contrast Ultrasound Examination for Lesion-Specific Diagnoses of the Target Lesion Against the Reference Diagnosis/Standard of Truth
Reader 3
|
15.8 percentage of participants
|
19.1 percentage of participants
|
Adverse Events
Sonazoid™
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
SonoVue®
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The only disclosure restriction on the PI and/or institution is that the Sponsor can review results communications prior to public release and can restrict communications regarding trial results for a period that is more than 30 days (publications/abstracts) but not to exceed 90 days (patent related issues) from the time submitted to the Sponsor to review. The PI may be asked to remove any Sponsor confidential information and/or delay publication to protect any proprietary information.
- Publication restrictions are in place
Restriction type: OTHER