Trial Outcomes & Findings for SonoVue®-Enhanced Ultrasound Versus Unenhanced US for Focal Liver Lesion Characterization (NCT NCT00788697)
NCT ID: NCT00788697
Last Updated: 2017-12-12
Results Overview
Sensitivity of SonoVue-enhanced ultrasound (SonoVue CE-US) versus unenhanced ultrasound (UE-US) for characterization of malignant focal liver lesions (FLLs), using the diagnosis provided by each of the 3 off-site assessors (blinded to patient data) for the Intent-to-Diagnose (ITD) population. Unit of analysis was the lesion, equivalent to the subject, since each subject had a single lesion that was to be characterized. True positive: subject with a target lesion characterized as malignant by both ultrasonography and the truth standard. Truth standard: contrast-enhanced computed tomography (CE CT) and /or contrast-enhanced magnetic resonance imaging (CE-MRI) examination OR tissue pathology/histology from surgical resection/biopsy OR 6-month follow up. Calculated as (number of true positive lesions/number of malignant lesions per truth standard) x 100.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
349 participants
Primary outcome timeframe
24 hours to 6 months
Results posted on
2017-12-12
Participant Flow
Study Initiation Date (first subject enrolled): 30 September 2009; Study completion date (last patient completed study related activities): 29 January 2013. The study was conducted at 14 investigational sites throughout the United States (USA) and 1 site in Europe.
A total of 74 patients received SonoVue in the training phase and were included only in safety population. A total of 263 patients received SonoVue in the efficacy phase. The 74 patients, included within the "Not Completed" category below, are the training patients.
Participant milestones
| Measure |
Safety Population
Interventions included SonoVue administration, unenhanced and SonoVue-enhanced ultrasound and definitive truth standard diagnosis.
Any patient who received SonoVue, training or efficacy phase, regardless of availability of ultrasonography or truth standard, is included in the Safety Population. Twelve patients with "No study drug administered" are not included in the Safety Population.
From 337 patients in the Safety Population, 74 patients enrolled in the training phase were excluded from efficacy analysis, and the Completed patients include efficacy phase patients who underwent SonoVue-enhanced ultrasound (SonoVue CE-US), unenhanced ultrasound (UE-US),and had definite truth standard diagnosis available.
|
|---|---|
|
Overall Study
STARTED
|
349
|
|
Overall Study
COMPLETED
|
240
|
|
Overall Study
NOT COMPLETED
|
109
|
Reasons for withdrawal
| Measure |
Safety Population
Interventions included SonoVue administration, unenhanced and SonoVue-enhanced ultrasound and definitive truth standard diagnosis.
Any patient who received SonoVue, training or efficacy phase, regardless of availability of ultrasonography or truth standard, is included in the Safety Population. Twelve patients with "No study drug administered" are not included in the Safety Population.
From 337 patients in the Safety Population, 74 patients enrolled in the training phase were excluded from efficacy analysis, and the Completed patients include efficacy phase patients who underwent SonoVue-enhanced ultrasound (SonoVue CE-US), unenhanced ultrasound (UE-US),and had definite truth standard diagnosis available.
|
|---|---|
|
Overall Study
No study drug administered
|
12
|
|
Overall Study
Training Patients
|
74
|
|
Overall Study
no truth standard procedure available
|
5
|
|
Overall Study
Technically inadequate truth standard
|
1
|
|
Overall Study
Indeterminate diagnosis from truth stand
|
17
|
Baseline Characteristics
SonoVue®-Enhanced Ultrasound Versus Unenhanced US for Focal Liver Lesion Characterization
Baseline characteristics by cohort
| Measure |
ITD Population
n=240 Participants
All patients who received SonoVue and enrolled in the efficacy phase, had a definite final diagnosis from truth standard and unenhanced and SonoVue-enhanced ultrasonography available
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
190 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
50 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
117 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
123 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
161 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black
|
32 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
15 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Other
|
32 participants
n=5 Participants
|
|
Region of Enrollment
United States
|
225 participants
n=5 Participants
|
|
Region of Enrollment
Europe
|
15 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 24 hours to 6 monthsPopulation: Among the 240 ITD participants, only 124 participants (lesions) were malignant based on the truth standard and were included for sensitivity.
Sensitivity of SonoVue-enhanced ultrasound (SonoVue CE-US) versus unenhanced ultrasound (UE-US) for characterization of malignant focal liver lesions (FLLs), using the diagnosis provided by each of the 3 off-site assessors (blinded to patient data) for the Intent-to-Diagnose (ITD) population. Unit of analysis was the lesion, equivalent to the subject, since each subject had a single lesion that was to be characterized. True positive: subject with a target lesion characterized as malignant by both ultrasonography and the truth standard. Truth standard: contrast-enhanced computed tomography (CE CT) and /or contrast-enhanced magnetic resonance imaging (CE-MRI) examination OR tissue pathology/histology from surgical resection/biopsy OR 6-month follow up. Calculated as (number of true positive lesions/number of malignant lesions per truth standard) x 100.
Outcome measures
| Measure |
Offsite Reader 1 - UE-US
n=124 Participants
Offsite Reader 1 unenhanced (UE) US assessment
|
Offsite Reader 1 SonoVue CE-US
n=124 Malignant lesions
Offsite Reader 1 SonoVue CE-US assessment
|
Offsite Reader 2 - UE-US
n=124 Malignant lesions
Offsite Reader 2 UE-US assessment
|
Offsite Reader 2 SonoVue CE-US
n=124 Malignant lesions
Offsite Reader 2 SonoVue CE-US assessment
|
Offsite Reader 3 UE-US
n=124 Malignant lesions
Offsite Reader 3 UE-US assessment
|
Offsite Reader 3 SonoVue CE-US
n=124 Malignant lesions
Offsite Reader 3 SonoVue CE-US assessment
|
|---|---|---|---|---|---|---|
|
Sensitivity: Percentage of True Positive Lesions Among All Malignant Lesions Per Truth Standard
|
53.2 Percentage of true positive lesions
Interval 44.4 to 62.0
|
64.5 Percentage of true positive lesions
Interval 56.1 to 72.9
|
41.1 Percentage of true positive lesions
Interval 32.5 to 49.8
|
60.5 Percentage of true positive lesions
Interval 51.9 to 69.1
|
66.1 Percentage of true positive lesions
Interval 57.8 to 74.5
|
46.8 Percentage of true positive lesions
Interval 38.0 to 55.6
|
PRIMARY outcome
Timeframe: 24 hours to 6 monthsPopulation: Among the 240 ITD participants, only 116 participants (lesions) were benign based on the truth standard and were included for specificity.
Specificity of SonoVue-enhanced versus unenhanced ultrasound for characterization of benign FLLs, using the diagnosis provided by each of the 3 off-site assessors (blinded to patient data) for the ITD population. Unit of analysis was the lesion, equivalent to the subject, since each subject had a single lesion that was to be characterized. True negative: subject with a target lesion characterized as benign by both ultrasonography and the truth standard. Truth standard: CE-CT and /or CE-MRI examination OR tissue pathology/histology from surgical resection/biopsy OR 6-month follow up. Calculated as (number of true negative lesions/number of benign lesions per truth standard) x 100.
Outcome measures
| Measure |
Offsite Reader 1 - UE-US
n=116 Benign lesions
Offsite Reader 1 unenhanced (UE) US assessment
|
Offsite Reader 1 SonoVue CE-US
n=116 Benign lesions
Offsite Reader 1 SonoVue CE-US assessment
|
Offsite Reader 2 - UE-US
n=116 Benign lesions
Offsite Reader 2 UE-US assessment
|
Offsite Reader 2 SonoVue CE-US
n=116 Benign lesions
Offsite Reader 2 SonoVue CE-US assessment
|
Offsite Reader 3 UE-US
n=116 Benign lesions
Offsite Reader 3 UE-US assessment
|
Offsite Reader 3 SonoVue CE-US
n=116 Benign lesions
Offsite Reader 3 SonoVue CE-US assessment
|
|---|---|---|---|---|---|---|
|
Specificity: Percentage of True Negative Lesions Among All Malignant Lesions Per Truth Standard
|
24.1 Percentage of true negative lesions
Interval 16.4 to 31.9
|
71.6 Percentage of true negative lesions
Interval 63.3 to 79.8
|
6.9 Percentage of true negative lesions
Interval 2.3 to 11.5
|
67.2 Percentage of true negative lesions
Interval 58.7 to 75.8
|
58.6 Percentage of true negative lesions
Interval 49.7 to 67.6
|
87.9 Percentage of true negative lesions
Interval 82.0 to 93.9
|
SECONDARY outcome
Timeframe: 24 hours to 6 monthsPopulation: 240 participants in the ITD population
The Accuracy of SonoVue-enhanced versus unenhanced ultrasound for characterization of malignant and benign FLLs, using the diagnosis provided by each of the 3 off-site assessors (blinded to patient data) for the ITD population Unit of analysis was the lesion, equivalent to the subject, since each subject had a single lesion that was to be characterized. True positive: subject with a target lesion characterized as malignant by both ultrasonography and the truth standard. True negative: subject with a target lesion characterized as benign by both ultrasonography and the truth standard. Truth standard: CE-CT and /or CE-MRI examination OR tissue pathology/histology from surgical resection/biopsy OR 6-month follow up. Calculated as (number of true positive and true negative lesions/number of total lesions per truth standard) x 100.
Outcome measures
| Measure |
Offsite Reader 1 - UE-US
n=240 Total lesions
Offsite Reader 1 unenhanced (UE) US assessment
|
Offsite Reader 1 SonoVue CE-US
n=240 Total lesions
Offsite Reader 1 SonoVue CE-US assessment
|
Offsite Reader 2 - UE-US
n=240 Total lesions
Offsite Reader 2 UE-US assessment
|
Offsite Reader 2 SonoVue CE-US
n=240 Total lesions
Offsite Reader 2 SonoVue CE-US assessment
|
Offsite Reader 3 UE-US
n=240 Total lesions
Offsite Reader 3 UE-US assessment
|
Offsite Reader 3 SonoVue CE-US
n=240 Total lesions
Offsite Reader 3 SonoVue CE-US assessment
|
|---|---|---|---|---|---|---|
|
Accuracy: Percentage of True Positive and True Negative Among All Lesions
|
39.2 Percent true positive and negative lesio
Interval 33.0 to 45.3
|
67.9 Percent true positive and negative lesio
Interval 62.0 to 73.8
|
24.6 Percent true positive and negative lesio
Interval 19.1 to 30.0
|
63.8 Percent true positive and negative lesio
Interval 57.7 to 69.8
|
62.5 Percent true positive and negative lesio
Interval 56.4 to 68.6
|
66.7 Percent true positive and negative lesio
Interval 60.7 to 72.6
|
SECONDARY outcome
Timeframe: 24 hours to 6 monthsPopulation: Among the 240 ITD participants, the overall number of participants (lesions) assessed as malignant varied based on the evaluation of the UE-US and CE-US made by each off-site Reader.
Positive Predictive Value of SonoVue-enhanced versus unenhanced ultrasound for characterization of FLLs, using the diagnosis provided by each of the 3 off-site assessors (blinded to patient data) for the ITD population. Unit of analysis was the lesion, equivalent to the subject, since each subject had a single lesion that was to be characterized. True positive: subject with a target lesion characterized as malignant by both ultrasonography and the truth standard. Truth standard: CE-CT and /or CE-MRI examination OR tissue pathology/histology from surgical resection/biopsy OR 6-month follow up. Calculated as (number of true positive lesions/number of malignant lesions per ultrasound) x 100.
Outcome measures
| Measure |
Offsite Reader 1 - UE-US
n=154 Positive lesions
Offsite Reader 1 unenhanced (UE) US assessment
|
Offsite Reader 1 SonoVue CE-US
n=113 Positive lesions
Offsite Reader 1 SonoVue CE-US assessment
|
Offsite Reader 2 - UE-US
n=159 Positive lesions
Offsite Reader 2 UE-US assessment
|
Offsite Reader 2 SonoVue CE-US
n=113 Positive lesions
Offsite Reader 2 SonoVue CE-US assessment
|
Offsite Reader 3 UE-US
n=130 Positive lesions
Offsite Reader 3 UE-US assessment
|
Offsite Reader 3 SonoVue CE-US
n=72 Positive lesions
Offsite Reader 3 SonoVue CE-US assessment
|
|---|---|---|---|---|---|---|
|
Positive Predictive Value (PPV): Percentage of True Positive Lesions Among All Malignant Lesions Per Ultrasound
|
42.9 Percent positive lesions by ultrasound
Interval 35.0 to 50.7
|
70.8 Percent positive lesions by ultrasound
Interval 62.4 to 79.2
|
32.1 Percent positive lesions by ultrasound
Interval 24.8 to 39.3
|
66.4 Percent positive lesions by ultrasound
Interval 57.7 to 75.1
|
63.1 Percent positive lesions by ultrasound
Interval 54.8 to 71.4
|
80.6 Percent positive lesions by ultrasound
Interval 71.4 to 89.7
|
SECONDARY outcome
Timeframe: 24 hours to 6 monthsPopulation: Among the 240 ITD participants, the overall number of participants (lesions) assessed as benign varied based on the evaluation of the UE-US and CE-US made by each off-site Reader.
Negative Predictive Value of SonoVue-enhanced versus unenhanced ultrasound for characterization of FLLs, using the diagnosis provided by each of the 3 off-site assessors (blinded to patient data) for the ITD population. Unit of analysis was the lesion, equivalent to the subject, since each subject had a single lesion that was to be characterized. True negative: subject with a target lesion characterized as benign by both ultrasonography and the truth standard. Truth standard: CE-CT and /or CE-MRI examination OR tissue pathology/histology from surgical resection/biopsy OR 6-month follow up. Calculated as (number of true negative lesions/number of benign lesions per ultrasound) x 100.
Outcome measures
| Measure |
Offsite Reader 1 - UE-US
n=86 Negative lesions
Offsite Reader 1 unenhanced (UE) US assessment
|
Offsite Reader 1 SonoVue CE-US
n=127 Negative lesions
Offsite Reader 1 SonoVue CE-US assessment
|
Offsite Reader 2 - UE-US
n=81 Negative lesions
Offsite Reader 2 UE-US assessment
|
Offsite Reader 2 SonoVue CE-US
n=127 Negative lesions
Offsite Reader 2 SonoVue CE-US assessment
|
Offsite Reader 3 UE-US
n=110 Negative lesions
Offsite Reader 3 UE-US assessment
|
Offsite Reader 3 SonoVue CE-US
n=168 Negative lesions
Offsite Reader 3 SonoVue CE-US assessment
|
|---|---|---|---|---|---|---|
|
Negative Predictive Value (NPV): Percentage of True Negative Lesions Among All Malignant Lesions Per Ultrasound
|
32.6 Percent negative lesions by ultrasound
Interval 22.7 to 42.5
|
65.4 Percent negative lesions by ultrasound
Interval 57.1 to 73.6
|
9.9 Percent negative lesions by ultrasound
Interval 3.4 to 16.4
|
61.4 Percent negative lesions by ultrasound
Interval 53.0 to 69.9
|
61.8 Percent negative lesions by ultrasound
Interval 52.7 to 70.9
|
60.7 Percent negative lesions by ultrasound
Interval 53.3 to 68.1
|
SECONDARY outcome
Timeframe: 24 hours to 6 monthsPopulation: Among the 124 ITD participants with malignant lesions based on the truth standard, only 115 participants (lesions) were characterized as either hepatocellular carcinoma (HCC) lesions or metastatic lesions.
SonoVue-enhanced versus unenhanced ultrasound for specific diagnosis of malignant FLLs, using the diagnosis provided by each of the 3 off-site assessors (blinded to patient data) for the ITD population. Unit of analysis was the lesion, equivalent to the subject, since each subject had a single lesion that was to be characterized. Truth standard: CE-CT and /or CE-MRI examination OR tissue pathology/histology from surgical resection/biopsy OR 6-month follow up. Calculated as (number of correctly characterized lesions/number of lesions per truth standard) x 100.
Outcome measures
| Measure |
Offsite Reader 1 - UE-US
n=115 Malignant lesions to be characterized
Offsite Reader 1 unenhanced (UE) US assessment
|
Offsite Reader 1 SonoVue CE-US
n=115 Malignant lesions to be characterized
Offsite Reader 1 SonoVue CE-US assessment
|
Offsite Reader 2 - UE-US
n=115 Malignant lesions to be characterized
Offsite Reader 2 UE-US assessment
|
Offsite Reader 2 SonoVue CE-US
n=115 Malignant lesions to be characterized
Offsite Reader 2 SonoVue CE-US assessment
|
Offsite Reader 3 UE-US
n=115 Malignant lesions to be characterized
Offsite Reader 3 UE-US assessment
|
Offsite Reader 3 SonoVue CE-US
n=115 Malignant lesions to be characterized
Offsite Reader 3 SonoVue CE-US assessment
|
|---|---|---|---|---|---|---|
|
Specific Diagnosis of Malignant FLLs
# of HCC by Truth Standard
|
84 Malignant lesions
|
84 Malignant lesions
|
84 Malignant lesions
|
84 Malignant lesions
|
84 Malignant lesions
|
84 Malignant lesions
|
|
Specific Diagnosis of Malignant FLLs
# HCC(Malignant) Correctly Characterized
|
29 Malignant lesions
|
33 Malignant lesions
|
12 Malignant lesions
|
13 Malignant lesions
|
21 Malignant lesions
|
20 Malignant lesions
|
|
Specific Diagnosis of Malignant FLLs
# of Metastasis by Truth Standard
|
31 Malignant lesions
|
31 Malignant lesions
|
31 Malignant lesions
|
31 Malignant lesions
|
31 Malignant lesions
|
31 Malignant lesions
|
|
Specific Diagnosis of Malignant FLLs
# Metastasis Correctly Characterized
|
14 Malignant lesions
|
20 Malignant lesions
|
16 Malignant lesions
|
17 Malignant lesions
|
19 Malignant lesions
|
21 Malignant lesions
|
SECONDARY outcome
Timeframe: 24 hours to 6 monthsPopulation: Among the 116 ITD participants with benign lesions based on the truth standard, only 89 participants (lesions) were characterized as either hemangioma or focal nodular hyperplasia.
SonoVue-enhanced versus unenhanced ultrasound for specific diagnosis of benign FLLs, using the diagnosis provided by each of the 3 off-site assessors (blinded to patient data) for the ITD population. Unit of analysis was the lesion, equivalent to the subject, since each subject had a single lesion that was to be characterized. Truth standard: CE-CT and /or CE-MRI examination OR tissue pathology/histology from surgical resection/biopsy OR 6-month follow up. Calculated as (number of correctly characterized lesions/number of lesions per truth standard) x 100.
Outcome measures
| Measure |
Offsite Reader 1 - UE-US
n=89 Benign lesions to be characterized
Offsite Reader 1 unenhanced (UE) US assessment
|
Offsite Reader 1 SonoVue CE-US
n=89 Benign lesions to be characterized
Offsite Reader 1 SonoVue CE-US assessment
|
Offsite Reader 2 - UE-US
n=89 Benign lesions to be characterized
Offsite Reader 2 UE-US assessment
|
Offsite Reader 2 SonoVue CE-US
n=89 Benign lesions to be characterized
Offsite Reader 2 SonoVue CE-US assessment
|
Offsite Reader 3 UE-US
n=89 Benign lesions to be characterized
Offsite Reader 3 UE-US assessment
|
Offsite Reader 3 SonoVue CE-US
n=89 Benign lesions to be characterized
Offsite Reader 3 SonoVue CE-US assessment
|
|---|---|---|---|---|---|---|
|
Specific Diagnosis of Benign FLLs
# Hemangioma Correctly Characterized
|
21 Benign lesions
|
47 Benign lesions
|
2 Benign lesions
|
40 Benign lesions
|
36 Benign lesions
|
50 Benign lesions
|
|
Specific Diagnosis of Benign FLLs
# of Hemangioma by Truth Standard
|
64 Benign lesions
|
64 Benign lesions
|
64 Benign lesions
|
64 Benign lesions
|
64 Benign lesions
|
64 Benign lesions
|
|
Specific Diagnosis of Benign FLLs
# of Focal nodular hyperplasia by Truth Standard
|
25 Benign lesions
|
25 Benign lesions
|
25 Benign lesions
|
25 Benign lesions
|
25 Benign lesions
|
25 Benign lesions
|
|
Specific Diagnosis of Benign FLLs
#Focal nodular hyperplasia Correctly Characterized
|
0 Benign lesions
|
10 Benign lesions
|
2 Benign lesions
|
13 Benign lesions
|
0 Benign lesions
|
12 Benign lesions
|
SECONDARY outcome
Timeframe: 24 hours to 6 monthsInter-reader agreement of assessment of malignant or benign by unenhanced and SonoVue-enhanced ultrasonography separately. Unit of analysis was the lesion, equivalent to the subject, since each subject had a single lesion that was to be characterized. Computation for the percentage agreement within two categories: "3 out of 3 readers agree" and "2 out of 3 readers agree".
Outcome measures
| Measure |
Offsite Reader 1 - UE-US
n=240 Participants
Offsite Reader 1 unenhanced (UE) US assessment
|
Offsite Reader 1 SonoVue CE-US
n=240 Participants
Offsite Reader 1 SonoVue CE-US assessment
|
Offsite Reader 2 - UE-US
Offsite Reader 2 UE-US assessment
|
Offsite Reader 2 SonoVue CE-US
Offsite Reader 2 SonoVue CE-US assessment
|
Offsite Reader 3 UE-US
Offsite Reader 3 UE-US assessment
|
Offsite Reader 3 SonoVue CE-US
Offsite Reader 3 SonoVue CE-US assessment
|
|---|---|---|---|---|---|---|
|
Inter-reader Agreement
% Agreement: 2 out of 3 off-site readers agree
|
97.1 Percent of total number of lesions
|
91.7 Percent of total number of lesions
|
—
|
—
|
—
|
—
|
|
Inter-reader Agreement
% Agreement: All 3 off-site readers agree
|
32.1 Percent of total number of lesions
|
51.7 Percent of total number of lesions
|
—
|
—
|
—
|
—
|
Adverse Events
Safety Population
Serious events: 5 serious events
Other events: 54 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Safety Population
n=337 participants at risk
Interventions included SonoVue administration, unenhanced and SonoVue-enhanced ultrasound and definitive truth standard diagnosis.
Any patient who received SonoVue, training or efficacy phase, regardless of availability of ultrasonography or truth standard, is included in the Safety Population. Twelve patients with "No study drug administered" are not included in the Safety Population.
Of 349 patients who started the study, 12 patients had "No study drug administered" and are not included and 337 received SonoVue and are included in the Safety Population.
|
|---|---|
|
Metabolism and nutrition disorders
Metabolic acidosis
|
0.30%
1/337 • Up to 7 days after contrast media injection
An AE was defined as any untoward medical occurrence in a patient or a clinical trial subject administered a medicinal product and that did not necessarily have to have a causal relationship with the use of the product. Any patient who received SonoVue is in the Safety Population. Of 349 patients who started the study, 12 had "No study drug administered" and are not included and 337 received SonoVue and are included in the Safety Population. All AEs were categorized using MedDRA 12.1.
|
|
Metabolism and nutrition disorders
Dehydration
|
0.30%
1/337 • Up to 7 days after contrast media injection
An AE was defined as any untoward medical occurrence in a patient or a clinical trial subject administered a medicinal product and that did not necessarily have to have a causal relationship with the use of the product. Any patient who received SonoVue is in the Safety Population. Of 349 patients who started the study, 12 had "No study drug administered" and are not included and 337 received SonoVue and are included in the Safety Population. All AEs were categorized using MedDRA 12.1.
|
|
Vascular disorders
Orthostatic hypotension
|
0.30%
1/337 • Up to 7 days after contrast media injection
An AE was defined as any untoward medical occurrence in a patient or a clinical trial subject administered a medicinal product and that did not necessarily have to have a causal relationship with the use of the product. Any patient who received SonoVue is in the Safety Population. Of 349 patients who started the study, 12 had "No study drug administered" and are not included and 337 received SonoVue and are included in the Safety Population. All AEs were categorized using MedDRA 12.1.
|
|
Nervous system disorders
Presyncope
|
0.30%
1/337 • Up to 7 days after contrast media injection
An AE was defined as any untoward medical occurrence in a patient or a clinical trial subject administered a medicinal product and that did not necessarily have to have a causal relationship with the use of the product. Any patient who received SonoVue is in the Safety Population. Of 349 patients who started the study, 12 had "No study drug administered" and are not included and 337 received SonoVue and are included in the Safety Population. All AEs were categorized using MedDRA 12.1.
|
|
Respiratory, thoracic and mediastinal disorders
Haemothorax
|
0.30%
1/337 • Up to 7 days after contrast media injection
An AE was defined as any untoward medical occurrence in a patient or a clinical trial subject administered a medicinal product and that did not necessarily have to have a causal relationship with the use of the product. Any patient who received SonoVue is in the Safety Population. Of 349 patients who started the study, 12 had "No study drug administered" and are not included and 337 received SonoVue and are included in the Safety Population. All AEs were categorized using MedDRA 12.1.
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.30%
1/337 • Up to 7 days after contrast media injection
An AE was defined as any untoward medical occurrence in a patient or a clinical trial subject administered a medicinal product and that did not necessarily have to have a causal relationship with the use of the product. Any patient who received SonoVue is in the Safety Population. Of 349 patients who started the study, 12 had "No study drug administered" and are not included and 337 received SonoVue and are included in the Safety Population. All AEs were categorized using MedDRA 12.1.
|
Other adverse events
| Measure |
Safety Population
n=337 participants at risk
Interventions included SonoVue administration, unenhanced and SonoVue-enhanced ultrasound and definitive truth standard diagnosis.
Any patient who received SonoVue, training or efficacy phase, regardless of availability of ultrasonography or truth standard, is included in the Safety Population. Twelve patients with "No study drug administered" are not included in the Safety Population.
Of 349 patients who started the study, 12 patients had "No study drug administered" and are not included and 337 received SonoVue and are included in the Safety Population.
|
|---|---|
|
Ear and labyrinth disorders
Tinnitus
|
0.30%
1/337 • Up to 7 days after contrast media injection
An AE was defined as any untoward medical occurrence in a patient or a clinical trial subject administered a medicinal product and that did not necessarily have to have a causal relationship with the use of the product. Any patient who received SonoVue is in the Safety Population. Of 349 patients who started the study, 12 had "No study drug administered" and are not included and 337 received SonoVue and are included in the Safety Population. All AEs were categorized using MedDRA 12.1.
|
|
Eye disorders
Conjunctival haemorrhage
|
0.30%
1/337 • Up to 7 days after contrast media injection
An AE was defined as any untoward medical occurrence in a patient or a clinical trial subject administered a medicinal product and that did not necessarily have to have a causal relationship with the use of the product. Any patient who received SonoVue is in the Safety Population. Of 349 patients who started the study, 12 had "No study drug administered" and are not included and 337 received SonoVue and are included in the Safety Population. All AEs were categorized using MedDRA 12.1.
|
|
Eye disorders
Conjunctival hyperaemia
|
0.30%
1/337 • Up to 7 days after contrast media injection
An AE was defined as any untoward medical occurrence in a patient or a clinical trial subject administered a medicinal product and that did not necessarily have to have a causal relationship with the use of the product. Any patient who received SonoVue is in the Safety Population. Of 349 patients who started the study, 12 had "No study drug administered" and are not included and 337 received SonoVue and are included in the Safety Population. All AEs were categorized using MedDRA 12.1.
|
|
Gastrointestinal disorders
Abdominal discomfort
|
0.59%
2/337 • Up to 7 days after contrast media injection
An AE was defined as any untoward medical occurrence in a patient or a clinical trial subject administered a medicinal product and that did not necessarily have to have a causal relationship with the use of the product. Any patient who received SonoVue is in the Safety Population. Of 349 patients who started the study, 12 had "No study drug administered" and are not included and 337 received SonoVue and are included in the Safety Population. All AEs were categorized using MedDRA 12.1.
|
|
Gastrointestinal disorders
Abdominal pain
|
1.2%
4/337 • Up to 7 days after contrast media injection
An AE was defined as any untoward medical occurrence in a patient or a clinical trial subject administered a medicinal product and that did not necessarily have to have a causal relationship with the use of the product. Any patient who received SonoVue is in the Safety Population. Of 349 patients who started the study, 12 had "No study drug administered" and are not included and 337 received SonoVue and are included in the Safety Population. All AEs were categorized using MedDRA 12.1.
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.30%
1/337 • Up to 7 days after contrast media injection
An AE was defined as any untoward medical occurrence in a patient or a clinical trial subject administered a medicinal product and that did not necessarily have to have a causal relationship with the use of the product. Any patient who received SonoVue is in the Safety Population. Of 349 patients who started the study, 12 had "No study drug administered" and are not included and 337 received SonoVue and are included in the Safety Population. All AEs were categorized using MedDRA 12.1.
|
|
Gastrointestinal disorders
Diarrhoea
|
0.89%
3/337 • Up to 7 days after contrast media injection
An AE was defined as any untoward medical occurrence in a patient or a clinical trial subject administered a medicinal product and that did not necessarily have to have a causal relationship with the use of the product. Any patient who received SonoVue is in the Safety Population. Of 349 patients who started the study, 12 had "No study drug administered" and are not included and 337 received SonoVue and are included in the Safety Population. All AEs were categorized using MedDRA 12.1.
|
|
Gastrointestinal disorders
Dry mouth
|
0.30%
1/337 • Up to 7 days after contrast media injection
An AE was defined as any untoward medical occurrence in a patient or a clinical trial subject administered a medicinal product and that did not necessarily have to have a causal relationship with the use of the product. Any patient who received SonoVue is in the Safety Population. Of 349 patients who started the study, 12 had "No study drug administered" and are not included and 337 received SonoVue and are included in the Safety Population. All AEs were categorized using MedDRA 12.1.
|
|
Gastrointestinal disorders
Nausea
|
2.7%
9/337 • Up to 7 days after contrast media injection
An AE was defined as any untoward medical occurrence in a patient or a clinical trial subject administered a medicinal product and that did not necessarily have to have a causal relationship with the use of the product. Any patient who received SonoVue is in the Safety Population. Of 349 patients who started the study, 12 had "No study drug administered" and are not included and 337 received SonoVue and are included in the Safety Population. All AEs were categorized using MedDRA 12.1.
|
|
Gastrointestinal disorders
Vomiting
|
0.89%
3/337 • Up to 7 days after contrast media injection
An AE was defined as any untoward medical occurrence in a patient or a clinical trial subject administered a medicinal product and that did not necessarily have to have a causal relationship with the use of the product. Any patient who received SonoVue is in the Safety Population. Of 349 patients who started the study, 12 had "No study drug administered" and are not included and 337 received SonoVue and are included in the Safety Population. All AEs were categorized using MedDRA 12.1.
|
|
General disorders
Chest pain
|
0.30%
1/337 • Up to 7 days after contrast media injection
An AE was defined as any untoward medical occurrence in a patient or a clinical trial subject administered a medicinal product and that did not necessarily have to have a causal relationship with the use of the product. Any patient who received SonoVue is in the Safety Population. Of 349 patients who started the study, 12 had "No study drug administered" and are not included and 337 received SonoVue and are included in the Safety Population. All AEs were categorized using MedDRA 12.1.
|
|
General disorders
Chills
|
0.30%
1/337 • Up to 7 days after contrast media injection
An AE was defined as any untoward medical occurrence in a patient or a clinical trial subject administered a medicinal product and that did not necessarily have to have a causal relationship with the use of the product. Any patient who received SonoVue is in the Safety Population. Of 349 patients who started the study, 12 had "No study drug administered" and are not included and 337 received SonoVue and are included in the Safety Population. All AEs were categorized using MedDRA 12.1.
|
|
General disorders
Fatigue
|
0.30%
1/337 • Up to 7 days after contrast media injection
An AE was defined as any untoward medical occurrence in a patient or a clinical trial subject administered a medicinal product and that did not necessarily have to have a causal relationship with the use of the product. Any patient who received SonoVue is in the Safety Population. Of 349 patients who started the study, 12 had "No study drug administered" and are not included and 337 received SonoVue and are included in the Safety Population. All AEs were categorized using MedDRA 12.1.
|
|
General disorders
Feeling hot
|
0.59%
2/337 • Up to 7 days after contrast media injection
An AE was defined as any untoward medical occurrence in a patient or a clinical trial subject administered a medicinal product and that did not necessarily have to have a causal relationship with the use of the product. Any patient who received SonoVue is in the Safety Population. Of 349 patients who started the study, 12 had "No study drug administered" and are not included and 337 received SonoVue and are included in the Safety Population. All AEs were categorized using MedDRA 12.1.
|
|
General disorders
Influenza like illness
|
0.30%
1/337 • Up to 7 days after contrast media injection
An AE was defined as any untoward medical occurrence in a patient or a clinical trial subject administered a medicinal product and that did not necessarily have to have a causal relationship with the use of the product. Any patient who received SonoVue is in the Safety Population. Of 349 patients who started the study, 12 had "No study drug administered" and are not included and 337 received SonoVue and are included in the Safety Population. All AEs were categorized using MedDRA 12.1.
|
|
General disorders
Injection site coldness
|
0.30%
1/337 • Up to 7 days after contrast media injection
An AE was defined as any untoward medical occurrence in a patient or a clinical trial subject administered a medicinal product and that did not necessarily have to have a causal relationship with the use of the product. Any patient who received SonoVue is in the Safety Population. Of 349 patients who started the study, 12 had "No study drug administered" and are not included and 337 received SonoVue and are included in the Safety Population. All AEs were categorized using MedDRA 12.1.
|
|
General disorders
Injection site pain
|
1.2%
4/337 • Up to 7 days after contrast media injection
An AE was defined as any untoward medical occurrence in a patient or a clinical trial subject administered a medicinal product and that did not necessarily have to have a causal relationship with the use of the product. Any patient who received SonoVue is in the Safety Population. Of 349 patients who started the study, 12 had "No study drug administered" and are not included and 337 received SonoVue and are included in the Safety Population. All AEs were categorized using MedDRA 12.1.
|
|
General disorders
Injection site swelling
|
0.30%
1/337 • Up to 7 days after contrast media injection
An AE was defined as any untoward medical occurrence in a patient or a clinical trial subject administered a medicinal product and that did not necessarily have to have a causal relationship with the use of the product. Any patient who received SonoVue is in the Safety Population. Of 349 patients who started the study, 12 had "No study drug administered" and are not included and 337 received SonoVue and are included in the Safety Population. All AEs were categorized using MedDRA 12.1.
|
|
General disorders
Pain
|
0.30%
1/337 • Up to 7 days after contrast media injection
An AE was defined as any untoward medical occurrence in a patient or a clinical trial subject administered a medicinal product and that did not necessarily have to have a causal relationship with the use of the product. Any patient who received SonoVue is in the Safety Population. Of 349 patients who started the study, 12 had "No study drug administered" and are not included and 337 received SonoVue and are included in the Safety Population. All AEs were categorized using MedDRA 12.1.
|
|
Hepatobiliary disorders
Gallbladder pain
|
0.30%
1/337 • Up to 7 days after contrast media injection
An AE was defined as any untoward medical occurrence in a patient or a clinical trial subject administered a medicinal product and that did not necessarily have to have a causal relationship with the use of the product. Any patient who received SonoVue is in the Safety Population. Of 349 patients who started the study, 12 had "No study drug administered" and are not included and 337 received SonoVue and are included in the Safety Population. All AEs were categorized using MedDRA 12.1.
|
|
Infections and infestations
Upper respiratory tract infection
|
0.30%
1/337 • Up to 7 days after contrast media injection
An AE was defined as any untoward medical occurrence in a patient or a clinical trial subject administered a medicinal product and that did not necessarily have to have a causal relationship with the use of the product. Any patient who received SonoVue is in the Safety Population. Of 349 patients who started the study, 12 had "No study drug administered" and are not included and 337 received SonoVue and are included in the Safety Population. All AEs were categorized using MedDRA 12.1.
|
|
Injury, poisoning and procedural complications
Procedural dizziness
|
0.30%
1/337 • Up to 7 days after contrast media injection
An AE was defined as any untoward medical occurrence in a patient or a clinical trial subject administered a medicinal product and that did not necessarily have to have a causal relationship with the use of the product. Any patient who received SonoVue is in the Safety Population. Of 349 patients who started the study, 12 had "No study drug administered" and are not included and 337 received SonoVue and are included in the Safety Population. All AEs were categorized using MedDRA 12.1.
|
|
Injury, poisoning and procedural complications
Procedural nausea
|
0.30%
1/337 • Up to 7 days after contrast media injection
An AE was defined as any untoward medical occurrence in a patient or a clinical trial subject administered a medicinal product and that did not necessarily have to have a causal relationship with the use of the product. Any patient who received SonoVue is in the Safety Population. Of 349 patients who started the study, 12 had "No study drug administered" and are not included and 337 received SonoVue and are included in the Safety Population. All AEs were categorized using MedDRA 12.1.
|
|
Injury, poisoning and procedural complications
Skin laceration
|
0.30%
1/337 • Up to 7 days after contrast media injection
An AE was defined as any untoward medical occurrence in a patient or a clinical trial subject administered a medicinal product and that did not necessarily have to have a causal relationship with the use of the product. Any patient who received SonoVue is in the Safety Population. Of 349 patients who started the study, 12 had "No study drug administered" and are not included and 337 received SonoVue and are included in the Safety Population. All AEs were categorized using MedDRA 12.1.
|
|
Investigations
Electrocardiogram T wave abnormal
|
0.30%
1/337 • Up to 7 days after contrast media injection
An AE was defined as any untoward medical occurrence in a patient or a clinical trial subject administered a medicinal product and that did not necessarily have to have a causal relationship with the use of the product. Any patient who received SonoVue is in the Safety Population. Of 349 patients who started the study, 12 had "No study drug administered" and are not included and 337 received SonoVue and are included in the Safety Population. All AEs were categorized using MedDRA 12.1.
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.30%
1/337 • Up to 7 days after contrast media injection
An AE was defined as any untoward medical occurrence in a patient or a clinical trial subject administered a medicinal product and that did not necessarily have to have a causal relationship with the use of the product. Any patient who received SonoVue is in the Safety Population. Of 349 patients who started the study, 12 had "No study drug administered" and are not included and 337 received SonoVue and are included in the Safety Population. All AEs were categorized using MedDRA 12.1.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.30%
1/337 • Up to 7 days after contrast media injection
An AE was defined as any untoward medical occurrence in a patient or a clinical trial subject administered a medicinal product and that did not necessarily have to have a causal relationship with the use of the product. Any patient who received SonoVue is in the Safety Population. Of 349 patients who started the study, 12 had "No study drug administered" and are not included and 337 received SonoVue and are included in the Safety Population. All AEs were categorized using MedDRA 12.1.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.59%
2/337 • Up to 7 days after contrast media injection
An AE was defined as any untoward medical occurrence in a patient or a clinical trial subject administered a medicinal product and that did not necessarily have to have a causal relationship with the use of the product. Any patient who received SonoVue is in the Safety Population. Of 349 patients who started the study, 12 had "No study drug administered" and are not included and 337 received SonoVue and are included in the Safety Population. All AEs were categorized using MedDRA 12.1.
|
|
Nervous system disorders
Dizziness
|
0.59%
2/337 • Up to 7 days after contrast media injection
An AE was defined as any untoward medical occurrence in a patient or a clinical trial subject administered a medicinal product and that did not necessarily have to have a causal relationship with the use of the product. Any patient who received SonoVue is in the Safety Population. Of 349 patients who started the study, 12 had "No study drug administered" and are not included and 337 received SonoVue and are included in the Safety Population. All AEs were categorized using MedDRA 12.1.
|
|
Nervous system disorders
Dysgeusia
|
3.0%
10/337 • Up to 7 days after contrast media injection
An AE was defined as any untoward medical occurrence in a patient or a clinical trial subject administered a medicinal product and that did not necessarily have to have a causal relationship with the use of the product. Any patient who received SonoVue is in the Safety Population. Of 349 patients who started the study, 12 had "No study drug administered" and are not included and 337 received SonoVue and are included in the Safety Population. All AEs were categorized using MedDRA 12.1.
|
|
Nervous system disorders
Headache
|
3.0%
10/337 • Up to 7 days after contrast media injection
An AE was defined as any untoward medical occurrence in a patient or a clinical trial subject administered a medicinal product and that did not necessarily have to have a causal relationship with the use of the product. Any patient who received SonoVue is in the Safety Population. Of 349 patients who started the study, 12 had "No study drug administered" and are not included and 337 received SonoVue and are included in the Safety Population. All AEs were categorized using MedDRA 12.1.
|
|
Nervous system disorders
Paraesthesia
|
0.30%
1/337 • Up to 7 days after contrast media injection
An AE was defined as any untoward medical occurrence in a patient or a clinical trial subject administered a medicinal product and that did not necessarily have to have a causal relationship with the use of the product. Any patient who received SonoVue is in the Safety Population. Of 349 patients who started the study, 12 had "No study drug administered" and are not included and 337 received SonoVue and are included in the Safety Population. All AEs were categorized using MedDRA 12.1.
|
|
Nervous system disorders
Parosmia
|
0.30%
1/337 • Up to 7 days after contrast media injection
An AE was defined as any untoward medical occurrence in a patient or a clinical trial subject administered a medicinal product and that did not necessarily have to have a causal relationship with the use of the product. Any patient who received SonoVue is in the Safety Population. Of 349 patients who started the study, 12 had "No study drug administered" and are not included and 337 received SonoVue and are included in the Safety Population. All AEs were categorized using MedDRA 12.1.
|
|
Psychiatric disorders
Delirium tremens
|
0.30%
1/337 • Up to 7 days after contrast media injection
An AE was defined as any untoward medical occurrence in a patient or a clinical trial subject administered a medicinal product and that did not necessarily have to have a causal relationship with the use of the product. Any patient who received SonoVue is in the Safety Population. Of 349 patients who started the study, 12 had "No study drug administered" and are not included and 337 received SonoVue and are included in the Safety Population. All AEs were categorized using MedDRA 12.1.
|
|
Psychiatric disorders
Insomnia
|
0.30%
1/337 • Up to 7 days after contrast media injection
An AE was defined as any untoward medical occurrence in a patient or a clinical trial subject administered a medicinal product and that did not necessarily have to have a causal relationship with the use of the product. Any patient who received SonoVue is in the Safety Population. Of 349 patients who started the study, 12 had "No study drug administered" and are not included and 337 received SonoVue and are included in the Safety Population. All AEs were categorized using MedDRA 12.1.
|
|
Respiratory, thoracic and mediastinal disorders
Diaphragmalgia
|
0.30%
1/337 • Up to 7 days after contrast media injection
An AE was defined as any untoward medical occurrence in a patient or a clinical trial subject administered a medicinal product and that did not necessarily have to have a causal relationship with the use of the product. Any patient who received SonoVue is in the Safety Population. Of 349 patients who started the study, 12 had "No study drug administered" and are not included and 337 received SonoVue and are included in the Safety Population. All AEs were categorized using MedDRA 12.1.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
0.30%
1/337 • Up to 7 days after contrast media injection
An AE was defined as any untoward medical occurrence in a patient or a clinical trial subject administered a medicinal product and that did not necessarily have to have a causal relationship with the use of the product. Any patient who received SonoVue is in the Safety Population. Of 349 patients who started the study, 12 had "No study drug administered" and are not included and 337 received SonoVue and are included in the Safety Population. All AEs were categorized using MedDRA 12.1.
|
|
Respiratory, thoracic and mediastinal disorders
Sinus congestion
|
0.30%
1/337 • Up to 7 days after contrast media injection
An AE was defined as any untoward medical occurrence in a patient or a clinical trial subject administered a medicinal product and that did not necessarily have to have a causal relationship with the use of the product. Any patient who received SonoVue is in the Safety Population. Of 349 patients who started the study, 12 had "No study drug administered" and are not included and 337 received SonoVue and are included in the Safety Population. All AEs were categorized using MedDRA 12.1.
|
|
Respiratory, thoracic and mediastinal disorders
Throat tightness
|
0.30%
1/337 • Up to 7 days after contrast media injection
An AE was defined as any untoward medical occurrence in a patient or a clinical trial subject administered a medicinal product and that did not necessarily have to have a causal relationship with the use of the product. Any patient who received SonoVue is in the Safety Population. Of 349 patients who started the study, 12 had "No study drug administered" and are not included and 337 received SonoVue and are included in the Safety Population. All AEs were categorized using MedDRA 12.1.
|
|
Respiratory, thoracic and mediastinal disorders
Erythema
|
0.30%
1/337 • Up to 7 days after contrast media injection
An AE was defined as any untoward medical occurrence in a patient or a clinical trial subject administered a medicinal product and that did not necessarily have to have a causal relationship with the use of the product. Any patient who received SonoVue is in the Safety Population. Of 349 patients who started the study, 12 had "No study drug administered" and are not included and 337 received SonoVue and are included in the Safety Population. All AEs were categorized using MedDRA 12.1.
|
|
Vascular disorders
Flushing
|
0.30%
1/337 • Up to 7 days after contrast media injection
An AE was defined as any untoward medical occurrence in a patient or a clinical trial subject administered a medicinal product and that did not necessarily have to have a causal relationship with the use of the product. Any patient who received SonoVue is in the Safety Population. Of 349 patients who started the study, 12 had "No study drug administered" and are not included and 337 received SonoVue and are included in the Safety Population. All AEs were categorized using MedDRA 12.1.
|
|
Vascular disorders
Hot flush
|
0.30%
1/337 • Up to 7 days after contrast media injection
An AE was defined as any untoward medical occurrence in a patient or a clinical trial subject administered a medicinal product and that did not necessarily have to have a causal relationship with the use of the product. Any patient who received SonoVue is in the Safety Population. Of 349 patients who started the study, 12 had "No study drug administered" and are not included and 337 received SonoVue and are included in the Safety Population. All AEs were categorized using MedDRA 12.1.
|
|
Vascular disorders
Pallor
|
0.30%
1/337 • Up to 7 days after contrast media injection
An AE was defined as any untoward medical occurrence in a patient or a clinical trial subject administered a medicinal product and that did not necessarily have to have a causal relationship with the use of the product. Any patient who received SonoVue is in the Safety Population. Of 349 patients who started the study, 12 had "No study drug administered" and are not included and 337 received SonoVue and are included in the Safety Population. All AEs were categorized using MedDRA 12.1.
|
Additional Information
Maria Luigia Storto, MD Executive Director X-Ray and Ultrasound Medical Affairs
Bracco Diagnostics Inc.
Phone: (609) 514-2200
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee Study results may be presented at scientific symposia or published in a peer-review journal after review by sponsor in accordance with the guidelines set forth in the applicable publication or financial agreement
- Publication restrictions are in place
Restriction type: OTHER