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

Primary Purpose

Liver Neoplasms

Status

Completed

Phase

Phase 3

Locations

United States

Study Type

Interventional

Intervention

SonoVue-enhanced ultrasound

Unenhanced ultrasound

About this trial

This is an interventional diagnostic trial for Liver Neoplasms

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 (βHCG) 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.

Sites / Locations

Bracco Diagnostics Inc

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

Patients who received SonoVue

Arm Description

Patients with at least 1 target lesion requiring work-up for characterization to undergo Unenhanced ultrasound of the target lesion (UE-US): gray scale and Doppler (color or power imaging) ultrasound investigations of the target lesion using commercially available ultrasound equipment and standard techniques (B-mode or Harmonic imaging) to study the anatomy of the target lesion and surrounding parenchyma; SonoVue-enhanced ultrasound of the target lesion (CE-US): procedures described in protocol Section 7.5.1.2, to study the lesion vascularity in comparison to the surrounding parenchyma; and Truth standard

Outcomes

Primary Outcome Measures

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.

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.

Secondary Outcome Measures

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.

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.

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.

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.

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.

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".

Full Information

NCT ID

NCT00788697

First Posted

November 7, 2008

Last Updated

November 13, 2017

Sponsor

Bracco Diagnostics, Inc

1. Study Identification

Unique Protocol Identification Number

NCT00788697

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

November 2017

Overall Recruitment Status

Completed

Study Start Date

September 2009 (undefined)

Primary Completion Date

July 2013 (Actual)

Study Completion Date

July 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Bracco Diagnostics, Inc

4. Oversight

Data Monitoring Committee

5. Study Description

Brief 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.

Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Liver Neoplasms

7. Study Design

Primary Purpose

Diagnostic

Study Phase

Phase 3

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

349 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Patients who received SonoVue

Arm Type

Other

Arm Description

Intervention Type

Drug

Intervention Name(s)

SonoVue-enhanced ultrasound

Other Intervention Name(s)

sulfur hexafluoride microbubbles

Intervention Description

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)

Intervention Type

Other

Intervention Name(s)

Unenhanced ultrasound

Intervention Description

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

Primary Outcome Measure Information:

Title

Sensitivity: Percentage of True Positive Lesions Among All Malignant Lesions Per Truth Standard

Description

Time Frame

24 hours to 6 months

Title

Specificity: Percentage of True Negative Lesions Among All Malignant Lesions Per Truth Standard

Description

Time Frame

24 hours to 6 months

Secondary Outcome Measure Information:

Title

Accuracy: Percentage of True Positive and True Negative Among All Lesions

Description

Time Frame

24 hours to 6 months

Title

Positive Predictive Value (PPV): Percentage of True Positive Lesions Among All Malignant Lesions Per Ultrasound

Description

Time Frame

24 hours to 6 months

Title

Negative Predictive Value (NPV): Percentage of True Negative Lesions Among All Malignant Lesions Per Ultrasound

Description

Time Frame

24 hours to 6 months

Title

Specific Diagnosis of Malignant FLLs

Description

Time Frame

24 hours to 6 months

Title

Specific Diagnosis of Benign FLLs

Description

Time Frame

24 hours to 6 months

Title

Inter-reader Agreement

Description

Time Frame

24 hours to 6 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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 (βHCG) 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Maria Luigia Storto, M.D.

Organizational Affiliation

Bracco Diagnostics, Inc

Official's Role

Study Chair

Facility Information:

Facility Name

Bracco Diagnostics Inc

City

Princeton

State/Province

New Jersey

ZIP/Postal Code

08540

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

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

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