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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00788697
First Posted: November 11, 2008
Last Update Posted: October 24, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Bracco Diagnostics, Inc
  Purpose
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.

Condition Intervention Phase
Liver Neoplasms Drug: SonoVue-enhanced ultrasound Other: Unenhanced ultrasound Phase 3

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
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

Resource links provided by NLM:


Further study details as provided by Bracco Diagnostics, Inc:

Primary Outcome Measures:
  • Sensitivity [ Time Frame: 24 hours to 6 months ]

    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.

    Among the 240 ITD participants, only 124 participants (lesions) were malignant based on 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 [ Time Frame: 24 hours to 6 months ]

    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.

    Among the 240 ITD participants, only 116 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.



Secondary Outcome Measures:
  • Accuracy [ Time Frame: 24 hours to 6 months ]

    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) [ Time Frame: 24 hours to 6 months ]

    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.

    Among the 240 ITD participants, the 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.

    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) [ Time Frame: 24 hours to 6 months ]

    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.

    Among the 240 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.

    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 [ Time Frame: 24 hours to 6 months ]

    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.

    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.

    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 [ Time Frame: 24 hours to 6 months ]

    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 116 ITD participants with benign lesions based on the truth standard, only 89 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.


  • Inter-reader Agreement [ Time Frame: 24 hours to 6 months ]
    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".


Enrollment: 349
Study Start Date: September 2009
Study Completion Date: July 2013
Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Patients who received SonoVue

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

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.
  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00788697


Locations
United States, New Jersey
Bracco Diagnostics Inc
Princeton, New Jersey, United States, 08540
Sponsors and Collaborators
Bracco Diagnostics, Inc
Investigators
Study Chair: Maria Luigia Storto, M.D. Bracco Diagnostics, Inc
  More Information

Responsible Party: Bracco Diagnostics, Inc
ClinicalTrials.gov Identifier: NCT00788697     History of Changes
Other Study ID Numbers: BR1-128
First Submitted: November 7, 2008
First Posted: November 11, 2008
Results First Submitted: September 28, 2016
Results First Posted: June 14, 2017
Last Update Posted: October 24, 2017
Last Verified: September 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Liver Diseases