SonoVue®-Enhanced Ultrasound Versus Unenhanced US for Focal Liver Lesion Characterization

Liver Neoplasms Clinical Trial

Official title:

Characterization of Focal Liver Lesions With SONOVUE®-Enhanced Ultrasound Imaging: A Phase III, Intrapatient Comparative Study Versus Un-enhanced Ultrasound Imaging Using Histology or Combined Imaging/Clinical Data as Truth Standard

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00788697
• Other study ID #: BR1-128
• Status: Completed
• Phase: Phase 3
• First received: November 7, 2008
• Last updated: November 13, 2017
• Start date: September 2009
• Est. completion date: July 2013

Study information

• Verified date: November 2017
• Source: Bracco Diagnostics, Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to demonstrate the superiority of SonoVue®-enhanced ultrasound versus unenhanced ultrasound for characterization of Focal Liver Lesions using final diagnosis based on histology or combined imaging/clinical data as truth standard.

Description:

Unit of analysis for the outcome measures was the lesion, equivalent to the subject, since each subject had a single lesion that was to be characterized.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 349
• Est. completion date: July 2013
• Est. primary completion date: July 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Male/female.

• Provides written Informed Consent and is willing to comply with protocol requirements.

• Is at least 18 years of age.

• Has at least 1 focal liver lesion (FLL) (target lesion) requiring work-up for characterization. Target lesions may include those:

• Incidentally detected,

• In subjects with chronic hepatitis or liver cirrhosis,

• In subjects with known history of malignancy.

• Is scheduled for surgical removal or biopsy of the target lesion from 24 hours to 30 days after the SonoVue® administration OR

• In case tissue biopsy is not indicated nor surgery planned, is scheduled for or has performed a contrast-enhanced (CE) CT and/or CE-MRI of the target lesion from 30 days to 48 hours prior to or from 24 hours to 30 days after the administration of SonoVue®.

Exclusion Criteria:

• Has an acoustic window insufficient for adequate ultrasound examination of the liver.

• Has a FLL that cannot be identified with unenhanced ultrasound.

• Has received or is scheduled for antineoplastic chemotherapy or an invasive procedure in the time period between test procedures and truth standard assessments which may have modified the target lesion.

• Is receiving any other contrast medium, within the 48 hours before and up to 24 hours following the administration of SonoVue®.

• Has previously been enrolled in and completed this study.

• Known right to left cardiac shunt, bidirectional or transient.

• Has any known allergy to 1 or more of the ingredients of the investigational product (sulfur hexafluoride or to any components of SonoVue®).

• Has any contraindication to 1 of the planned imaging procedures (ultrasound, CT or MRI), e.g., implants, claustrophobia, inadequate medical conditions etc.

• Has received an investigational compound within 30 days before admission into this study.

• Has any medical condition or other circumstances which would significantly decrease the chances of obtaining reliable data, achieving study objectives, or completing the study and/or post-dose follow-up examinations.

• Is determined by the Investigator that the subject is clinically unsuitable for the study.

• Is a pregnant or lactating female. Exclude the possibility of pregnancy by:

• testing on site at the institution serum beta-human chorionic gonadotropin (ßHCG) within 24 hours prior to the start of SonoVue® administration,

• surgical history (e.g., tubal ligation or hysterectomy),

• post menopausal with a minimum 1 year without menses.

Related Conditions & MeSH terms

• Liver Neoplasms

Intervention

Drug:
• SonoVue-enhanced ultrasound
Contrast-enhanced ultrasound (CE-US) examination of the target lesion. Drug: SonoVue® Dose of 2.4 mL bolus injection administered intravenously. Maximum of 2 injections (4.8 mL)

Other:
• Unenhanced ultrasound
-Unenhanced: Gray scale and Doppler (color or power imaging) ultrasound investigations of the target lesion. Drug: None

Locations

Country	Name	City	State
United States	Bracco Diagnostics Inc	Princeton	New Jersey

Sponsors (1)

Lead Sponsor	Collaborator
Bracco Diagnostics, Inc

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Sensitivity: Percentage of True Positive Lesions Among All Malignant Lesions Per Truth Standard	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.	24 hours to 6 months
Primary	Specificity: Percentage of True Negative Lesions Among All Malignant Lesions Per Truth Standard	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.	24 hours to 6 months
Secondary	Accuracy: Percentage of True Positive and True Negative Among All Lesions	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.	24 hours to 6 months
Secondary	Positive Predictive Value (PPV): Percentage of True Positive Lesions Among All Malignant Lesions Per Ultrasound	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.	24 hours to 6 months
Secondary	Negative Predictive Value (NPV): Percentage of True Negative Lesions Among All Malignant Lesions Per Ultrasound	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.	24 hours to 6 months
Secondary	Specific Diagnosis of Malignant FLLs	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.	24 hours to 6 months
Secondary	Specific Diagnosis of Benign FLLs	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.	24 hours to 6 months
Secondary	Inter-reader Agreement	Inter-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".	24 hours to 6 months