Trial Outcomes & Findings for SonoVue®-Enhanced Ultrasound (US) Versus Unenhanced US for Focal Liver Lesion Characterization (NCT NCT00829413)
NCT ID: NCT00829413
Last Updated: 2018-08-03
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 subject, since each subject had a single lesion 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 truth standard) x 100
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
353 participants
Primary outcome timeframe
24 hours to 6 months
Results posted on
2018-08-03
Participant Flow
Study Initiation Date (first subject enrolled): 15 June 2010; Study completion date (last patient completed study related activities): 18 February 2013. The study was conducted at 18 investigational sites; 11 sites throughout the United States (USA), 5 sites in Europe, and 2 sites in Canada.
A total of 67 patients received SonoVue in the training phase and were included only in safety population. A total of 259 patients received SonoVue in the efficacy phase. The 67 patients, included within the "Not Completed" category below, are the training patients.
Participant milestones
| Measure |
Safety Population
Interventions included SonoVue administration, unenhanced (UE-US) and SonoVue-enhanced ultrasound (CE-US) and definitive truth standard diagnosis.
Any patient who received SonoVue is included in the Safety Population. Thirteen patients who started had "No study drug administered" and are not included in the Safety Population.
Among patients in the Safety Population, 67 training phase patients were excluded from efficacy analysis. Completed patients included efficacy phase patients who underwent unenhanced and SonoVue-enhanced ultrasound and had definite truth standard diagnosis available.
|
|---|---|
|
Overall Study
STARTED
|
353
|
|
Overall Study
COMPLETED
|
259
|
|
Overall Study
NOT COMPLETED
|
94
|
Reasons for withdrawal
| Measure |
Safety Population
Interventions included SonoVue administration, unenhanced (UE-US) and SonoVue-enhanced ultrasound (CE-US) and definitive truth standard diagnosis.
Any patient who received SonoVue is included in the Safety Population. Thirteen patients who started had "No study drug administered" and are not included in the Safety Population.
Among patients in the Safety Population, 67 training phase patients were excluded from efficacy analysis. Completed patients included efficacy phase patients who underwent unenhanced and SonoVue-enhanced ultrasound and had definite truth standard diagnosis available.
|
|---|---|
|
Overall Study
No study drug admimnistered
|
13
|
|
Overall Study
Training Patients
|
67
|
|
Overall Study
No truth standard procedure available
|
9
|
|
Overall Study
Technically inadequate truth standard
|
2
|
|
Overall Study
Indeterminate diagnosis from truth stand
|
3
|
Baseline Characteristics
SonoVue®-Enhanced Ultrasound (US) Versus Unenhanced US for Focal Liver Lesion Characterization
Baseline characteristics by cohort
| Measure |
ITD Population
n=259 Participants
All patients who were enrolled in the efficacy phase, received SonoVue, 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
|
185 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
74 Participants
n=5 Participants
|
|
Age, Continuous
|
56.9 years
STANDARD_DEVIATION 13.4 • n=5 Participants
|
|
Sex: Female, Male
Female
|
123 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
136 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
206 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black
|
22 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
12 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Other
|
19 participants
n=5 Participants
|
|
Region of Enrollment
United States
|
132 participants
n=5 Participants
|
|
Region of Enrollment
Europe
|
93 participants
n=5 Participants
|
|
Region of Enrollment
Canada
|
34 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 24 hours to 6 monthsPopulation: Among 259 ITD subjects, 119 were malignant by 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 subject, since each subject had a single lesion 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 truth standard) x 100
Outcome measures
| Measure |
Offsite Reader 1 UE-US
n=119 Malignant lesions
Offsite Reader 1 UE-US assessment
|
Offsite Reader 1 SonoVue CE-US
n=119 Malignant lesions
Offsite Reader 1 SonoVue CE-US assessment
|
Offsite Reader 2 UE-US
n=119 Malignant lesions
Offsite Reader 2 UE-US assessment
|
Offsite Reader 2 SonoVue CE-US
n=119 Malignant lesions
Offsite Reader 2 SonoVue CE-US assessment
|
Offsite Reader 3 UE-US
n=119 Malignant lesions
Offsite Reader 3 UE-US assessment
|
Offsite Reader 3 SonoVue CE-US
n=119 Malignant lesions
Offsite Reader 3 SonoVue CE-US assessment
|
|---|---|---|---|---|---|---|
|
Sensitivity: Percentage of True Positive Lesions Among All Malignant Lesions Per Truth Standard
|
48.7 Percentage of true positive lesions
Interval 39.8 to 57.7
|
86.6 Percentage of true positive lesions
Interval 80.4 to 92.7
|
35.3 Percentage of true positive lesions
Interval 26.7 to 43.9
|
75.6 Percentage of true positive lesions
Interval 67.9 to 83.3
|
16.0 Percentage of true positive lesions
Interval 9.4 to 22.5
|
91.6 Percentage of true positive lesions
Interval 86.6 to 96.6
|
PRIMARY outcome
Timeframe: 24 hours to 6 monthsPopulation: Among the 259 ITD participants, only 140 participants (lesions) were benign based on the truth standard and were were included for specificty.
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 truth standard. Among the 259 ITD participants, only 140 participants (lesions) were benign based on 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=140 Benign lesions
Offsite Reader 1 UE-US assessment
|
Offsite Reader 1 SonoVue CE-US
n=140 Participants
Offsite Reader 1 SonoVue CE-US assessment
|
Offsite Reader 2 UE-US
n=140 Participants
Offsite Reader 2 UE-US assessment
|
Offsite Reader 2 SonoVue CE-US
n=140 Participants
Offsite Reader 2 SonoVue CE-US assessment
|
Offsite Reader 3 UE-US
n=140 Participants
Offsite Reader 3 UE-US assessment
|
Offsite Reader 3 SonoVue CE-US
n=140 Participants
Offsite Reader 3 SonoVue CE-US assessment
|
|---|---|---|---|---|---|---|
|
Specificity: Percentage of True Negative Lesions Among All Benign Lesions Per Truth Standard'
|
62.9 Percentage of true benign lesions
Interval 54.9 to 70.9
|
70.7 Percentage of true benign lesions
Interval 63.2 to 78.3
|
54.3 Percentage of true benign lesions
Interval 46.0 to 62.5
|
82.9 Percentage of true benign lesions
Interval 76.6 to 89.1
|
22.1 Percentage of true benign lesions
Interval 15.3 to 29.0
|
72.9 Percentage of true benign lesions
Interval 65.5 to 80.2
|
SECONDARY outcome
Timeframe: 24 hours to 6 monthsPopulation: 259 participants in the ITD population
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 truth standard. True negative: subject with a target lesion characterized as benign by both ultrasonography and 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=259 Total lesions
Offsite Reader 1 UE-US assessment
|
Offsite Reader 1 SonoVue CE-US
n=259 Total lesions
Offsite Reader 1 SonoVue CE-US assessment
|
Offsite Reader 2 UE-US
n=259 Total lesions
Offsite Reader 2 UE-US assessment
|
Offsite Reader 2 SonoVue CE-US
n=259 Total lesions
Offsite Reader 2 SonoVue CE-US assessment
|
Offsite Reader 3 UE-US
n=259 Total lesions
Offsite Reader 3 UE-US assessment
|
Offsite Reader 3 SonoVue CE-US
n=259 Total lesions
Offsite Reader 3 SonoVue CE-US assessment
|
|---|---|---|---|---|---|---|
|
Accuracy: Percentage of True Positive and True Negative Among All Lesions
|
56.4 Percent true positive and negative lesio
Interval 50.3 to 62.4
|
78.0 Percent true positive and negative lesio
Interval 72.9 to 83.0
|
45.6 Percent true positive and negative lesio
Interval 39.5 to 51.6
|
79.5 Percent true positive and negative lesio
Interval 74.6 to 84.5
|
19.3 Percent true positive and negative lesio
Interval 14.5 to 24.1
|
81.5 Percent true positive and negative lesio
Interval 76.7 to 86.2
|
SECONDARY outcome
Timeframe: 24 hours to 6 monthsPopulation: Among the 259 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 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=110 Positive lesions
Offsite Reader 1 UE-US assessment
|
Offsite Reader 1 SonoVue CE-US
n=144 Positive lesions
Offsite Reader 1 SonoVue CE-US assessment
|
Offsite Reader 2 UE-US
n=106 Positive lesions
Offsite Reader 2 UE-US assessment
|
Offsite Reader 2 SonoVue CE-US
n=114 Positive lesions
Offsite Reader 2 SonoVue CE-US assessment
|
Offsite Reader 3 UE-US
n=128 Positive lesions
Offsite Reader 3 UE-US assessment
|
Offsite Reader 3 SonoVue CE-US
n=147 Positive lesions
Offsite Reader 3 SonoVue CE-US assessment
|
|---|---|---|---|---|---|---|
|
Positive Predictive Value [PPV]: Percentage of True Positive Lesions Among All Malignant Lesions Per Ultrasound
|
52.7 Percent positive lesions by ultrasound
Interval 43.4 to 62.1
|
71.5 Percent positive lesions by ultrasound
Interval 64.2 to 78.9
|
39.6 Percent positive lesions by ultrasound
Interval 30.3 to 48.9
|
78.9 Percent positive lesions by ultrasound
Interval 71.5 to 86.4
|
14.8 Percent positive lesions by ultrasound
Interval 8.7 to 21.0
|
74.1 Percent positive lesions by ultrasound
Interval 67.1 to 81.2
|
SECONDARY outcome
Timeframe: 24 hours to 6 monthsPopulation: Among the 259 ITD participants, the 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 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=149 Negative lesions
Offsite Reader 1 UE-US assessment
|
Offsite Reader 1 SonoVue CE-US
n=115 Negative lesions
Offsite Reader 1 SonoVue CE-US assessment
|
Offsite Reader 2 UE-US
n=153 Negative lesions
Offsite Reader 2 UE-US assessment
|
Offsite Reader 2 SonoVue CE-US
n=145 Negative lesions
Offsite Reader 2 SonoVue CE-US assessment
|
Offsite Reader 3 UE-US
n=131 Negative lesions
Offsite Reader 3 UE-US assessment
|
Offsite Reader 3 SonoVue CE-US
n=112 Negative lesions
Offsite Reader 3 SonoVue CE-US assessment
|
|---|---|---|---|---|---|---|
|
Negative Predictive Value [NPV]: Percentage of True Negative Lesions Among All Benign Lesions Per Ultrasound
|
59.1 Percent negative lesions by ultrasound
Interval 51.2 to 67.0
|
86.1 Percent negative lesions by ultrasound
Interval 79.8 to 92.4
|
49.7 Percent negative lesions by ultrasound
Interval 41.8 to 57.6
|
80.0 Percent negative lesions by ultrasound
Interval 73.5 to 86.5
|
23.7 Percent negative lesions by ultrasound
Interval 16.4 to 30.9
|
91.1 Percent negative lesions by ultrasound
Interval 85.8 to 96.4
|
SECONDARY outcome
Timeframe: 24 hours to 6 monthsPopulation: Among the 119 ITD participants with malignant lesions based on the truth standard, only 94 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=94 Malignant lesions to be characterized
Offsite Reader 1 UE-US assessment
|
Offsite Reader 1 SonoVue CE-US
n=94 Malignant lesions to be characterized
Offsite Reader 1 SonoVue CE-US assessment
|
Offsite Reader 2 UE-US
n=94 Malignant lesions to be characterized
Offsite Reader 2 UE-US assessment
|
Offsite Reader 2 SonoVue CE-US
n=94 Malignant lesions to be characterized
Offsite Reader 2 SonoVue CE-US assessment
|
Offsite Reader 3 UE-US
n=94 Malignant lesions to be characterized
Offsite Reader 3 UE-US assessment
|
Offsite Reader 3 SonoVue CE-US
n=94 Malignant lesions to be characterized
Offsite Reader 3 SonoVue CE-US assessment
|
|---|---|---|---|---|---|---|
|
Specific Diagnosis of Malignant FLLs
# of HCC by Truth Standard
|
47 Malignant lesions
|
47 Malignant lesions
|
47 Malignant lesions
|
47 Malignant lesions
|
47 Malignant lesions
|
47 Malignant lesions
|
|
Specific Diagnosis of Malignant FLLs
# HCC(Malignant) Correctly Characterized
|
16 Malignant lesions
|
26 Malignant lesions
|
10 Malignant lesions
|
29 Malignant lesions
|
3 Malignant lesions
|
30 Malignant lesions
|
|
Specific Diagnosis of Malignant FLLs
# of Metastasis by Truth Standard
|
47 Malignant lesions
|
47 Malignant lesions
|
47 Malignant lesions
|
47 Malignant lesions
|
47 Malignant lesions
|
47 Malignant lesions
|
|
Specific Diagnosis of Malignant FLLs
# Metastasis Correctly Characterized
|
18 Malignant lesions
|
37 Malignant lesions
|
12 Malignant lesions
|
31 Malignant lesions
|
1 Malignant lesions
|
28 Malignant lesions
|
SECONDARY outcome
Timeframe: 24 hours to 6 monthsPopulation: Among the 140 ITD participants with benign lesions based on the truth standard, only 91 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. Among the 140 ITD participants with benign lesions based on the truth standard, only 91 participants (lesions) were characterized as either hemangioma or focal nodular hyperplasia. 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=91 Benign lesions to be characterized
Offsite Reader 1 UE-US assessment
|
Offsite Reader 1 SonoVue CE-US
n=91 Benign lesions to be characterized
Offsite Reader 1 SonoVue CE-US assessment
|
Offsite Reader 2 UE-US
n=91 Benign lesions to be characterized
Offsite Reader 2 UE-US assessment
|
Offsite Reader 2 SonoVue CE-US
n=91 Benign lesions to be characterized
Offsite Reader 2 SonoVue CE-US assessment
|
Offsite Reader 3 UE-US
n=91 Benign lesions to be characterized
Offsite Reader 3 UE-US assessment
|
Offsite Reader 3 SonoVue CE-US
n=91 Benign lesions to be characterized
Offsite Reader 3 SonoVue CE-US assessment
|
|---|---|---|---|---|---|---|
|
Specific Diagnosis of Benign FLLs
# of Hemangioma by Truth Standard
|
52 Benign lesions
|
52 Benign lesions
|
52 Benign lesions
|
52 Benign lesions
|
52 Benign lesions
|
52 Benign lesions
|
|
Specific Diagnosis of Benign FLLs
# Hemangioma Correctly Characterized
|
28 Benign lesions
|
38 Benign lesions
|
30 Benign lesions
|
43 Benign lesions
|
12 Benign lesions
|
38 Benign lesions
|
|
Specific Diagnosis of Benign FLLs
# of Focal nodular hyperplasia by Truth Standard
|
39 Benign lesions
|
39 Benign lesions
|
39 Benign lesions
|
39 Benign lesions
|
39 Benign lesions
|
39 Benign lesions
|
|
Specific Diagnosis of Benign FLLs
#Focal nodular hyperplasia Correctly Characterized
|
15 Benign lesions
|
23 Benign lesions
|
8 Benign lesions
|
22 Benign lesions
|
2 Benign lesions
|
18 Benign lesions
|
SECONDARY outcome
Timeframe: 24 hours to 6 monthsKappa statistic based on assessment of malignant or benign by unenhanced and SonoVue-enhanced ultrasonography separately and 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=259 Participants
Offsite Reader 1 UE-US assessment
|
Offsite Reader 1 SonoVue CE-US
n=259 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: All 3 off-site readers agree
|
28.2 Percentage of agreement
|
66.0 Percentage of agreement
|
—
|
—
|
—
|
—
|
|
Inter-reader Agreement
% Agreement: 2 out of 3 off-site readers agree
|
94.6 Percentage of agreement
|
99.6 Percentage of agreement
|
—
|
—
|
—
|
—
|
Adverse Events
Safety Population
Serious events: 4 serious events
Other events: 45 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Safety Population
n=340 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.
|
|---|---|
|
Metabolism and nutrition disorders
Dehydration
|
0.29%
1/340 • Adverse events were monitored from the time of signing the Informed Consent Form through 7 days after SonoVue administration.
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 353 patients who started the study, 13 had "No study drug administered" and are not included and 340 received SonoVue and are included in the Safety Population. All AEs were categorized using MedDRA 12.1.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon cancer metastatic
|
0.29%
1/340 • Adverse events were monitored from the time of signing the Informed Consent Form through 7 days after SonoVue administration.
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 353 patients who started the study, 13 had "No study drug administered" and are not included and 340 received SonoVue and are included in the Safety Population. All AEs were categorized using MedDRA 12.1.
|
|
Hepatobiliary disorders
Hepatic hemorrhage
|
0.29%
1/340 • Adverse events were monitored from the time of signing the Informed Consent Form through 7 days after SonoVue administration.
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 353 patients who started the study, 13 had "No study drug administered" and are not included and 340 received SonoVue and are included in the Safety Population. All AEs were categorized using MedDRA 12.1.
|
|
Gastrointestinal disorders
Rectal haemorrhage
|
0.29%
1/340 • Adverse events were monitored from the time of signing the Informed Consent Form through 7 days after SonoVue administration.
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 353 patients who started the study, 13 had "No study drug administered" and are not included and 340 received SonoVue and are included in the Safety Population. All AEs were categorized using MedDRA 12.1.
|
Other adverse events
| Measure |
Safety Population
n=340 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.
|
|---|---|
|
General disorders
Chest pain
|
0.29%
1/340 • Adverse events were monitored from the time of signing the Informed Consent Form through 7 days after SonoVue administration.
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 353 patients who started the study, 13 had "No study drug administered" and are not included and 340 received SonoVue and are included in the Safety Population. All AEs were categorized using MedDRA 12.1.
|
|
Ear and labyrinth disorders
Tinnitus
|
0.29%
1/340 • Adverse events were monitored from the time of signing the Informed Consent Form through 7 days after SonoVue administration.
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 353 patients who started the study, 13 had "No study drug administered" and are not included and 340 received SonoVue and are included in the Safety Population. All AEs were categorized using MedDRA 12.1.
|
|
Gastrointestinal disorders
Abdominal discomfort
|
0.29%
1/340 • Adverse events were monitored from the time of signing the Informed Consent Form through 7 days after SonoVue administration.
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 353 patients who started the study, 13 had "No study drug administered" and are not included and 340 received SonoVue and are included in the Safety Population. All AEs were categorized using MedDRA 12.1.
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.29%
1/340 • Adverse events were monitored from the time of signing the Informed Consent Form through 7 days after SonoVue administration.
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 353 patients who started the study, 13 had "No study drug administered" and are not included and 340 received SonoVue and are included in the Safety Population. All AEs were categorized using MedDRA 12.1.
|
|
Gastrointestinal disorders
Abdominal tenderness
|
0.29%
1/340 • Adverse events were monitored from the time of signing the Informed Consent Form through 7 days after SonoVue administration.
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 353 patients who started the study, 13 had "No study drug administered" and are not included and 340 received SonoVue and are included in the Safety Population. All AEs were categorized using MedDRA 12.1.
|
|
Gastrointestinal disorders
Diarrhea
|
1.2%
4/340 • Adverse events were monitored from the time of signing the Informed Consent Form through 7 days after SonoVue administration.
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 353 patients who started the study, 13 had "No study drug administered" and are not included and 340 received SonoVue and are included in the Safety Population. All AEs were categorized using MedDRA 12.1.
|
|
Gastrointestinal disorders
Dyspepsia
|
0.59%
2/340 • Adverse events were monitored from the time of signing the Informed Consent Form through 7 days after SonoVue administration.
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 353 patients who started the study, 13 had "No study drug administered" and are not included and 340 received SonoVue and are included in the Safety Population. All AEs were categorized using MedDRA 12.1.
|
|
Gastrointestinal disorders
Flatulence
|
0.88%
3/340 • Adverse events were monitored from the time of signing the Informed Consent Form through 7 days after SonoVue administration.
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 353 patients who started the study, 13 had "No study drug administered" and are not included and 340 received SonoVue and are included in the Safety Population. All AEs were categorized using MedDRA 12.1.
|
|
Gastrointestinal disorders
Gastroesophageal reflux disease
|
0.29%
1/340 • Adverse events were monitored from the time of signing the Informed Consent Form through 7 days after SonoVue administration.
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 353 patients who started the study, 13 had "No study drug administered" and are not included and 340 received SonoVue and are included in the Safety Population. All AEs were categorized using MedDRA 12.1.
|
|
Gastrointestinal disorders
Nausea
|
1.8%
6/340 • Adverse events were monitored from the time of signing the Informed Consent Form through 7 days after SonoVue administration.
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 353 patients who started the study, 13 had "No study drug administered" and are not included and 340 received SonoVue and are included in the Safety Population. All AEs were categorized using MedDRA 12.1.
|
|
Gastrointestinal disorders
Toothache
|
0.29%
1/340 • Adverse events were monitored from the time of signing the Informed Consent Form through 7 days after SonoVue administration.
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 353 patients who started the study, 13 had "No study drug administered" and are not included and 340 received SonoVue and are included in the Safety Population. All AEs were categorized using MedDRA 12.1.
|
|
Gastrointestinal disorders
Vomiting
|
0.29%
1/340 • Adverse events were monitored from the time of signing the Informed Consent Form through 7 days after SonoVue administration.
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 353 patients who started the study, 13 had "No study drug administered" and are not included and 340 received SonoVue and are included in the Safety Population. All AEs were categorized using MedDRA 12.1.
|
|
General disorders
Asthenia
|
0.29%
1/340 • Adverse events were monitored from the time of signing the Informed Consent Form through 7 days after SonoVue administration.
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 353 patients who started the study, 13 had "No study drug administered" and are not included and 340 received SonoVue and are included in the Safety Population. All AEs were categorized using MedDRA 12.1.
|
|
General disorders
Chest discomfort
|
0.29%
1/340 • Adverse events were monitored from the time of signing the Informed Consent Form through 7 days after SonoVue administration.
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 353 patients who started the study, 13 had "No study drug administered" and are not included and 340 received SonoVue and are included in the Safety Population. All AEs were categorized using MedDRA 12.1.
|
|
General disorders
Fatigue
|
0.59%
2/340 • Adverse events were monitored from the time of signing the Informed Consent Form through 7 days after SonoVue administration.
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 353 patients who started the study, 13 had "No study drug administered" and are not included and 340 received SonoVue and are included in the Safety Population. All AEs were categorized using MedDRA 12.1.
|
|
General disorders
Injection site haemorrhage
|
0.29%
1/340 • Adverse events were monitored from the time of signing the Informed Consent Form through 7 days after SonoVue administration.
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 353 patients who started the study, 13 had "No study drug administered" and are not included and 340 received SonoVue and are included in the Safety Population. All AEs were categorized using MedDRA 12.1.
|
|
General disorders
Injection site irritation
|
0.29%
1/340 • Adverse events were monitored from the time of signing the Informed Consent Form through 7 days after SonoVue administration.
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 353 patients who started the study, 13 had "No study drug administered" and are not included and 340 received SonoVue and are included in the Safety Population. All AEs were categorized using MedDRA 12.1.
|
|
General disorders
Injection site pain
|
0.59%
2/340 • Adverse events were monitored from the time of signing the Informed Consent Form through 7 days after SonoVue administration.
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 353 patients who started the study, 13 had "No study drug administered" and are not included and 340 received SonoVue and are included in the Safety Population. All AEs were categorized using MedDRA 12.1.
|
|
General disorders
Malaise
|
0.29%
1/340 • Adverse events were monitored from the time of signing the Informed Consent Form through 7 days after SonoVue administration.
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 353 patients who started the study, 13 had "No study drug administered" and are not included and 340 received SonoVue and are included in the Safety Population. All AEs were categorized using MedDRA 12.1.
|
|
Hepatobiliary disorders
Hepatic pain
|
0.29%
1/340 • Adverse events were monitored from the time of signing the Informed Consent Form through 7 days after SonoVue administration.
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 353 patients who started the study, 13 had "No study drug administered" and are not included and 340 received SonoVue and are included in the Safety Population. All AEs were categorized using MedDRA 12.1.
|
|
Injury, poisoning and procedural complications
Procedural pain
|
0.29%
1/340 • Adverse events were monitored from the time of signing the Informed Consent Form through 7 days after SonoVue administration.
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 353 patients who started the study, 13 had "No study drug administered" and are not included and 340 received SonoVue and are included in the Safety Population. All AEs were categorized using MedDRA 12.1.
|
|
Investigations
Basophil count increased
|
0.29%
1/340 • Adverse events were monitored from the time of signing the Informed Consent Form through 7 days after SonoVue administration.
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 353 patients who started the study, 13 had "No study drug administered" and are not included and 340 received SonoVue and are included in the Safety Population. All AEs were categorized using MedDRA 12.1.
|
|
Investigations
Blood creatinine increased
|
0.29%
1/340 • Adverse events were monitored from the time of signing the Informed Consent Form through 7 days after SonoVue administration.
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 353 patients who started the study, 13 had "No study drug administered" and are not included and 340 received SonoVue and are included in the Safety Population. All AEs were categorized using MedDRA 12.1.
|
|
Investigations
Electrocardiogram abnormal
|
0.29%
1/340 • Adverse events were monitored from the time of signing the Informed Consent Form through 7 days after SonoVue administration.
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 353 patients who started the study, 13 had "No study drug administered" and are not included and 340 received SonoVue and are included in the Safety Population. All AEs were categorized using MedDRA 12.1.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
0.29%
1/340 • Adverse events were monitored from the time of signing the Informed Consent Form through 7 days after SonoVue administration.
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 353 patients who started the study, 13 had "No study drug administered" and are not included and 340 received SonoVue and are included in the Safety Population. All AEs were categorized using MedDRA 12.1.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.29%
1/340 • Adverse events were monitored from the time of signing the Informed Consent Form through 7 days after SonoVue administration.
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 353 patients who started the study, 13 had "No study drug administered" and are not included and 340 received SonoVue and are included in the Safety Population. All AEs were categorized using MedDRA 12.1.
|
|
Musculoskeletal and connective tissue disorders
Groin pain
|
0.29%
1/340 • Adverse events were monitored from the time of signing the Informed Consent Form through 7 days after SonoVue administration.
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 353 patients who started the study, 13 had "No study drug administered" and are not included and 340 received SonoVue and are included in the Safety Population. All AEs were categorized using MedDRA 12.1.
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
0.59%
2/340 • Adverse events were monitored from the time of signing the Informed Consent Form through 7 days after SonoVue administration.
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 353 patients who started the study, 13 had "No study drug administered" and are not included and 340 received SonoVue and are included in the Safety Population. All AEs were categorized using MedDRA 12.1.
|
|
Nervous system disorders
Dizziness
|
0.88%
3/340 • Adverse events were monitored from the time of signing the Informed Consent Form through 7 days after SonoVue administration.
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 353 patients who started the study, 13 had "No study drug administered" and are not included and 340 received SonoVue and are included in the Safety Population. All AEs were categorized using MedDRA 12.1.
|
|
Nervous system disorders
Dysgeusia
|
0.29%
1/340 • Adverse events were monitored from the time of signing the Informed Consent Form through 7 days after SonoVue administration.
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 353 patients who started the study, 13 had "No study drug administered" and are not included and 340 received SonoVue and are included in the Safety Population. All AEs were categorized using MedDRA 12.1.
|
|
Nervous system disorders
Headache
|
1.8%
6/340 • Adverse events were monitored from the time of signing the Informed Consent Form through 7 days after SonoVue administration.
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 353 patients who started the study, 13 had "No study drug administered" and are not included and 340 received SonoVue and are included in the Safety Population. All AEs were categorized using MedDRA 12.1.
|
|
Nervous system disorders
Paraesthesia
|
0.29%
1/340 • Adverse events were monitored from the time of signing the Informed Consent Form through 7 days after SonoVue administration.
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 353 patients who started the study, 13 had "No study drug administered" and are not included and 340 received SonoVue and are included in the Safety Population. All AEs were categorized using MedDRA 12.1.
|
|
Nervous system disorders
Parosmia
|
0.29%
1/340 • Adverse events were monitored from the time of signing the Informed Consent Form through 7 days after SonoVue administration.
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 353 patients who started the study, 13 had "No study drug administered" and are not included and 340 received SonoVue and are included in the Safety Population. All AEs were categorized using MedDRA 12.1.
|
|
Psychiatric disorders
Hallucination
|
0.29%
1/340 • Adverse events were monitored from the time of signing the Informed Consent Form through 7 days after SonoVue administration.
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 353 patients who started the study, 13 had "No study drug administered" and are not included and 340 received SonoVue and are included in the Safety Population. All AEs were categorized using MedDRA 12.1.
|
|
Psychiatric disorders
Insomnia
|
0.29%
1/340 • Adverse events were monitored from the time of signing the Informed Consent Form through 7 days after SonoVue administration.
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 353 patients who started the study, 13 had "No study drug administered" and are not included and 340 received SonoVue and are included in the Safety Population. All AEs were categorized using MedDRA 12.1.
|
|
Renal and urinary disorders
Renal pain
|
0.29%
1/340 • Adverse events were monitored from the time of signing the Informed Consent Form through 7 days after SonoVue administration.
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 353 patients who started the study, 13 had "No study drug administered" and are not included and 340 received SonoVue and are included in the Safety Population. All AEs were categorized using MedDRA 12.1.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.29%
1/340 • Adverse events were monitored from the time of signing the Informed Consent Form through 7 days after SonoVue administration.
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 353 patients who started the study, 13 had "No study drug administered" and are not included and 340 received SonoVue and are included in the Safety Population. All AEs were categorized using MedDRA 12.1.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.59%
2/340 • Adverse events were monitored from the time of signing the Informed Consent Form through 7 days after SonoVue administration.
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 353 patients who started the study, 13 had "No study drug administered" and are not included and 340 received SonoVue and are included in the Safety Population. All AEs were categorized using MedDRA 12.1.
|
|
Skin and subcutaneous tissue disorders
Night sweats
|
0.29%
1/340 • Adverse events were monitored from the time of signing the Informed Consent Form through 7 days after SonoVue administration.
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 353 patients who started the study, 13 had "No study drug administered" and are not included and 340 received SonoVue and are included in the Safety Population. All AEs were categorized using MedDRA 12.1.
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.29%
1/340 • Adverse events were monitored from the time of signing the Informed Consent Form through 7 days after SonoVue administration.
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 353 patients who started the study, 13 had "No study drug administered" and are not included and 340 received SonoVue and are included in the Safety Population. All AEs were categorized using MedDRA 12.1.
|
|
Vascular disorders
Flushing
|
0.29%
1/340 • Adverse events were monitored from the time of signing the Informed Consent Form through 7 days after SonoVue administration.
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 353 patients who started the study, 13 had "No study drug administered" and are not included and 340 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