Point-of-care Ultrasound Screening and Assessment of Chronic Liver Diseases and NASH (POCUS-NASH)

Evaluation of Diagnostic Performances of a New Point-of-care Ultrasound System for the Detection of Fibrotic NASH and the Assessment of Liver Disease Severity in Patients With Known or Suspected Chronic Liver Disease

The main objective of the study is to determine the diagnostic performances of an ultraportable diagnostic ultrasound system for the assessment of liver fibrosis severity in patients with NASH, and to compare them to other non-invasive tests.

Study Overview

• Status: Not yet recruiting
• Conditions: Liver Diseases; Liver Cirrhosis; Fibrosis, Liver; NASH - Nonalcoholic Steatohepatitis; Non-Alcoholic Fatty Liver Disease; Steatosis of Liver
• Intervention / Treatment: Device: Ultrasound liver assessment

Detailed Description

This is a prospective cross-sectional study that will recruit approximately 1000 patients across 30 clinical sites in Europe and the USA.

The target recruited population will include adult patients at risk of, or with known chronic liver diseases, whether or not screened for inclusion in NASH pharmaceutical trials.

After being informed about the study objectives and potential risks, patients who consent to participate will undergo an non-invasive external ultrasound exam of their liver using an ultraportable diagnostic ultrasound system. The system will derive quantitative information related to physical and acoustic properties of the liver tissue, which are known to correlate with the severity of chronic diffuse liver diseases such as fibrosis and steatosis.

The study will also assess the repeatability, reproducibility and robustness of quantitative parameters. Collected data will also enable exploring ultrasound-based liver tissue characterization correlated to NASH-specific histological lesions such as intra-hepatic inflammation and hepatic cell ballooning.

• Study Type: Interventional
• Enrollment (Anticipated): 1000
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Any of the following criteria:

  • Patients with known chronic liver diseases referred to liver-specific exams by their referring physician as part of the routine practice, including a VCTE exam, with or without a blood test, a MRI/MRE exam, a liver biopsy,
  • Patients screened for fibrotic NASH in the context of NASH pharmaceutical trials, for which a data sharing agreement has been signed between E-Scopics and the pharmaceutical trial promoter,
• Patients who consent in written to participate in the Clinical Investigation after being orally informed on the objectives and methods of the Clinical Investigation,
• European patients covered by a social security program

Exclusion Criteria:

• Patients under 18 years of age or over 80 years of age,
• Patients with active implants such as pacemakers, defibrillators, pumps, etc.
• Patients presenting wounds at the location where the ES1 probe shall be placed on patients' skin,
• Adult patients under social tutorship, or unable to provide informed consent when not subject to tutorship measures,
• Pregnant and breastfeeding women,
• People deprived of their freedom rights
• People who have been hospitalized without giving informed consent or under emergency situation,
• People admitted in a social or sanitary institution for other reasons than the Clinical Investigation,
• Patients included in another research study that could interfere with the present Clinical Investigation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Main arm; Main study arm	Device: Ultrasound liver assessment; The intervention consists in an ultrasound exam performed with the ultrasound medical device subject of the research.; Other Names: Elastography; Ultrasound attenuation; Sound speed

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Elastography diagnostic performance	Differences between areas under ROC curves for the ES1 liver stiffness measurement, used as a diagnostic measure of liver fibrosis severity, and other methods, in NASH patients.	At study completion, 1 year
Diagnostic performance estimates	Estimates of diagnostic performances at a defined cutoff, for binary diagnostic objectives (detect ≥ F2, ≥ F3, or F4): Sensitivity, specificity, and diagnostic accuracy; Positive and negative predictive values	At study completion, 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Liver stiffness robustness indicators	Dispersion and standard deviation of measurements; Intra-class Correlation Coefficients (ICC) and 95% confidence intervals for intra-operator repeatability; Intra-class Correlation Coefficients (ICC) and 95% confidence intervals for inter-operator reproducibility; Intra-subject variance; Intra-operator variance; Standard error on measurements	At study completion, 1 year
Equivalence with other methods	R² correlation coefficient and p-value between ES1 and VCTE liver stiffness measurements; R² correlation coefficient and p-value between ES1 and MRE liver stiffness measurements; Average of quadratic errors between 2 equipment; Concordance Correlation Coefficients (CCC) and 95% confidence intervals	At study completion, 1 year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploratory outcome 1: Liver steatosis	R² correlation coefficient and p-value between ES1 ultrasound attenuation measurements and MRI PDFF; Concordance Correlation Coefficients (CCC) and 95% confidence intervals, and Bland-Altman graphs between ultrasound attenuation measurements and MRI PDFF; R² correlation coefficient and p-value between ES1 speed of sound measurements and MRI PDFF; Concordance Correlation Coefficients (CCC) and 95% confidence intervals, and Bland-Altman graphs between speed of sound measurements and MRI PDFF	At study completion, 1 year
Exploratory outcome 2: Intra-hepatic inflammation and/or hepatocytes ballooning	Correlation coefficients between ES1 parameters or combinations of parameters and histological scoring for lobular inflammation (A0 to A3) and/or ballooning.; If relevant, area under the ROC curve for combinations of ES1 parameters or combinations of parameters used as a diagnostic measures of liver inflammation severity using histological scoring for lobular inflammation (A0 to A3); If relevant for given binary diagnostic objectives (detect ≥ A1, ≥ A2, or A3), calculate optimal diagnostic cutoffs and estimate diagnostic performances	At study completion, 1 year
Exploratory outcome 3: Liver NAS Score	Correlation coefficients between ES1 parameters or combinations of parameters and histological NAS score (NAS 0 to NAS 8).; If relevant, area under the ROC curve for combinations of ES1 parameters or combinations of parameters used as a diagnostic measure of NAFLD-related activity using the histological NAS score (0 to 8); If relevant, for given binary diagnostic objectives (detect < NAS 3, ≥ NAS 3, ≥ NAS 5), calculate optimal diagnostic cutoffs and estimate diagnostic performances	At study completion, 1 year

Collaborators and Investigators

• Sponsor: E-Scopics

Study record dates

Study Major Dates

• Study Start (Anticipated): September 1, 2022
• Primary Completion (Anticipated): September 1, 2023
• Study Completion (Anticipated): September 1, 2023

Study Registration Dates

• First Submitted: November 3, 2021
• First Submitted That Met QC Criteria: November 3, 2021
• First Posted (Actual): November 15, 2021

Study Record Updates

• Last Update Posted (Actual): August 23, 2022
• Last Update Submitted That Met QC Criteria: August 22, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: Ultrasound; Elastography; Sound speed; Ultrasound attenuation
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Fibrosis; Liver Diseases; Fatty Liver; Liver Cirrhosis; Non-alcoholic Fatty Liver Disease
• Other Study ID Numbers: ES211

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No