ESCULAP: Standardized CEUS Algorithms for Diagnosis of HCC - Prospective German Multicenter Study

Sponsor

University Hospital Erlangen (Other)

Overall Status

Completed

CT.gov ID

NCT03405909

Collaborator

(none)

517

Enrollment

Location

11.5

Actual Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Aim of this prospective national multicenter study is to improve standardization of contrast-enhanced ultrasound (CEUS) in the non-invasive diagnosis of hepatocellular carcinoma (HCC) in high-risk patients.

The study is funded by the German Society for Ultrasound in Medicine (DEGUM).

Condition or Disease	Intervention/Treatment	Phase
Hepatocellular Carcinoma Cholangiocarcinoma, Intrahepatic Liver Cirrhosis Liver Cancer Liver Neoplasms Liver Diseases	Diagnostic Test: contrast enhanced ultrasound (CEUS) Diagnostic Test: MRI Diagnostic Test: Histology

Detailed Description

To date, CEUS criteria for non-invasive diagnosis of HCC include arterial phase hyperenhancement, followed by contrast washout in the portal venous or late phase. We would like to investigate the following points:

whether arterial hyperenhancement alone is sufficient for the definite diagnosis of HCC in cirrhosis with CEUS
whether a further clearly-defined point of assessment in the late phase after 4-6 minutes is of additional diagnostic value in focal liver lesions showing no contrast washout after 3 minutes
diagnostic value of CEUS-based standardised diagnostic algorithms (ESCULAP = Erlanger Synopsis of Contrast Enhanced Ultrasound for Liver lesion Assessment in Patients at risk; CEUS LI-RADS = Contrast Enhanced Ultrasound Liver Imaging Reporting and Data System) for non-invasive diagnosis of HCC in high-risk patients (diagnostic accuracy, interobserver-variability, feasability in clinical Routine).

Study Design

Study Type:

Observational

Actual Enrollment :

517 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Standardized Contrast-enhanced Ultrasound (CEUS) -Algorithms for the Non-invasive Diagnosis of Hepatocellular Carcinoma (HCC) in High-risk-patients - a Prospective German Multicenter Study

Actual Study Start Date :

Apr 21, 2018

Actual Primary Completion Date :

Apr 6, 2019

Actual Study Completion Date :

Apr 6, 2019

Arms and Interventions

Arm	Intervention/Treatment
Patients at risk for HCC Patients with any of the following conditions: liver cirrhosis of any origin chronic hepatitis B infection chronic hepatitis C infection with advanced fibrosis non-alcoholic steatohepatitis (NASH) hemochromatosis Interventions: B-mode ultrasound, contrast enhanced ultrasound (CEUS); MRI / histology	Diagnostic Test: contrast enhanced ultrasound (CEUS) CEUS with SonoVue following standardized protocol Diagnostic Test: MRI CE-MRI following standardized protocol Diagnostic Test: Histology diagnostic liver biopsy

Arm

Intervention/Treatment

Patients at risk for HCC

Patients with any of the following conditions: liver cirrhosis of any origin chronic hepatitis B infection chronic hepatitis C infection with advanced fibrosis non-alcoholic steatohepatitis (NASH) hemochromatosis Interventions: B-mode ultrasound, contrast enhanced ultrasound (CEUS); MRI / histology

Diagnostic Test: contrast enhanced ultrasound (CEUS)

CEUS with SonoVue following standardized protocol

Diagnostic Test: MRI

CE-MRI following standardized protocol

Diagnostic Test: Histology

diagnostic liver biopsy

Outcome Measures

Primary Outcome Measures

Diagnostic value of standardised CEUS-based algorithms for the non-invasive diagnosis of HCC in high-risk patients [2 years]
Diagnostic accuracy, interobserver-variabilty and feasability in clinical routine for CEUS-based algorithms Reference Standard: histology / MRI

Secondary Outcome Measures

Diagnostic value / dispensability of contrast washout for definite diagnosis of HCC with CEUS [2 years]
Sensitvity, specificity, positive and negative predictive value of arterial hyperenhancement only compared with arterial hyperenhancement followed by contrast washout for non-invasive diagnosis of HCC in high-risk patients Reference Standard: histology / MRI
Standardisation of CEUS examinations [2 years]
Diagnostic value of an additional standardised examination point in the late phase after 4-6 minutes in lesions without contrast washout after 3 minutes Reference Standard: histology / MRI
Diagnostic accuracy of CEUS in intrahepatic cholangiocellular carcinoma (ICC) [2 years]
Sensitvity, specificity, positive and negative predictive value of contrast-enhanced ultrasound for non-invasive diagnosis of ICC in high-risk patients / differential diagnosis of HCC versus ICC Reference Standard: histology
Comparison of two CEUS-based algorithms [2 years]
ESCULAP versus CEUS LI-RADS (diagnostic accuracy, interobserver agreement) Reference Standard: histology / MRI
Non-inferiority of CEUS versus MRI for non-invasive diagnosis of HCC [2 years]
Comparison of CEUS and MRI for non-invasive diagnosis of HCC (diagnostic accuracy, interobserver agreement) Reference Standard: histology
Influence of histological grading on contrast enhancement behaviour [2 years]
correlation of histological grading and contrast enhancement pattern

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

high risk for HCC
focal liver lesion on B-mode ultrasound

Exclusion Criteria:

pre-treated HCC lesion
systemic therapy for HCC (sorafenib, regorafenib and others)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University Hospital Erlangen, Department of Medicine 1	Erlangen	Bavaria	Germany	91054

Sponsors and Collaborators

University Hospital Erlangen

Investigators

Principal Investigator: Barbara Schellhaas, MD, University Hospital Erlangen, Department of Medicine 1
Principal Investigator: Deike Strobel, MD, University Hospital Erlangen, Department of Medicine 1