Characterization Of Focal Liver Lesions With Sonovue®-Enhanced Ultrasound Imaging: A Phase III, Intrapatient Comparative Study Versus Unenhanced Ultrasound Imaging Using Histology Or Combined Imaging/Clinical Data As Truth Standard
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- Bracco Diagnostics, Inc
- Enrollment
- 353
- Locations
- 1
- Primary Endpoint
- Specificity: Percentage of True Negative Lesions Among All Benign Lesions Per Truth Standard'
Study Overview
Brief Summary
The purpose of this study is to demonstrate the Sensitivity and Specificity of SonoVue®-enhanced ultrasound is superior to that of unenhanced ultrasound for the characterization of benign versus malignant FLLs using final diagnosis based on histology or combined imaging (CE-CT and/or CE MRI)/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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Diagnostic
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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 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 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 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.
Arms & Interventions
Patients who received SonoVue
Patients with at least one target lesions 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
2.4 mL of sulfur hexafluoride microbubbles (SonoVue®) will be administered as a bolus injection in a peripheral vein.
Intervention: SonoVue® (Drug)
Outcomes
Primary Outcomes
Specificity: Percentage of True Negative Lesions Among All Benign Lesions Per Truth Standard'
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 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.
Sensitivity: Percentage of True Positive Lesions Among All Malignant Lesions Per Truth Standard
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 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
Secondary Outcomes
- Accuracy: Percentage of True Positive and True Negative Among All Lesions(24 hours to 6 months)
- Positive Predictive Value [PPV]: Percentage of True Positive Lesions Among All Malignant Lesions Per Ultrasound(24 hours to 6 months)
- Negative Predictive Value [NPV]: Percentage of True Negative Lesions Among All Benign Lesions Per Ultrasound(24 hours to 6 months)
- Specific Diagnosis of Malignant FLLs(24 hours to 6 months)
- Specific Diagnosis of Benign FLLs(24 hours to 6 months)
- Inter-reader Agreement(24 hours to 6 months)