REVISE-HCC: Real-world Elecsys® GAAD Implementation and Validation to Improve Surveillance and Early Detection of HCC

Sponsor

Manchester University NHS Foundation Trust (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05971108

Collaborator

University of Manchester (Other), Roche Pharma AG (Industry), Unity Insights (Other), Imperial College London (Other)

600

Enrollment

Arm

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

Patients with liver cirrhosis are at high risk of developing hepatocellular carcinoma (HCC) which implies significant mortality. At present current surveillance methods detect hepatocellular carcinomas at a late stage resulting in few treatment options for patients and, in the majority of cases, premature death.

The goal of this study is to implement Elecsys® GAAD in real-world hepatocellular carcinoma surveillance for those with liver cirrhosis.

The main questions it aims to answer are:

Does the introduction of the Elecsys® GAAD algorithm to the surveillance pathway increase early detection of HCC?
Does the introduction of the Elecsys® GAAD algorithm to the surveillance pathway reduce false positive tests and unnecessary confirmatory investigations?
Does the new surveillance pathway improve adherence?

Researchers will compare Elecsys® GAAD with standard of care tests to see if it results in earlier detection of hepatocellular carcinoma and will explore potential improvements to the surveillance pathway.

Condition or Disease	Intervention/Treatment	Phase
Liver Cirrhosis Hepatocellular Carcinoma	Diagnostic Test: Elecsys® GAAD	N/A

Study Design

Study Type:

Interventional

Anticipated Enrollment :

600 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Diagnostic

Official Title:

Real-world Elecsys® GAAD Algorithm Implementation and Validation to Improve Surveillance and Early Detection of Hepatocellular Carcinoma

Anticipated Study Start Date :

Aug 1, 2023

Anticipated Primary Completion Date :

Jul 31, 2030

Anticipated Study Completion Date :

Jul 31, 2030

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Patients with liver cirrhosis eligible for HCC Surveillance Real-world HCC surveillance cohort will be exposed to Elecsys® GAAD in parallel with standard of care tests.	Diagnostic Test: Elecsys® GAAD Elecsys® GAAD is a CE marked in vitro diagnostic (IVD) multivariate index assay, intended as an aid in the diagnosis of early-stage HCC. It provides a semi quantitative result by combining in an algorithm the quantitative measurements of Elecsys® AFP (alpha-fetoprotein) and Elecsys® PIVKA-II (protein induced by vitamin K absence II) levels in serum and plasma, with gender and age. Clinical evidence showed that Elecsys® GAAD had high performance in detecting HCC (sensitivity 86.5%), particularly early stage (sensitivity 78.9%), with 91.4% specificity for both early and all stages, out-performing current standard of care (Chan et al. 2021). Elecsys® GAAD may be integrated into current surveillance practice to increase early-stage HCC detection rate, reduce unnecessary onward investigations and patient anxiety.

Arm

Intervention/Treatment

Experimental: Patients with liver cirrhosis eligible for HCC Surveillance

Real-world HCC surveillance cohort will be exposed to Elecsys® GAAD in parallel with standard of care tests.

Diagnostic Test: Elecsys® GAAD

Elecsys® GAAD is a CE marked in vitro diagnostic (IVD) multivariate index assay, intended as an aid in the diagnosis of early-stage HCC. It provides a semi quantitative result by combining in an algorithm the quantitative measurements of Elecsys® AFP (alpha-fetoprotein) and Elecsys® PIVKA-II (protein induced by vitamin K absence II) levels in serum and plasma, with gender and age. Clinical evidence showed that Elecsys® GAAD had high performance in detecting HCC (sensitivity 86.5%), particularly early stage (sensitivity 78.9%), with 91.4% specificity for both early and all stages, out-performing current standard of care (Chan et al. 2021). Elecsys® GAAD may be integrated into current surveillance practice to increase early-stage HCC detection rate, reduce unnecessary onward investigations and patient anxiety.

Outcome Measures

Primary Outcome Measures

Incidence of hepatocellular carcinoma diagnosis [2 years]
Incidence recorded as number of cases per study cohort
Stage of hepatocellular carcinoma at diagnosis [2 years]
Barcelona Clinic Liver Cancer (BCLC) stage 0-D

Secondary Outcome Measures

Rates of false positives for each combination of diagnostic tests [2 years]
Count (%) of True/False positives for each test (against magnetic resonance imaging (MRI) / computerised tomography (CT)) will be reported. Results from different tests (and their (meaningful) combination) will be tabulated against each other: Alpha-fetoprotein (AFP) vs GAAD Ultrasound scan (USS) vs GAAD AFP+ USS vs GAAD AFP+USS vs GAAD +USS AFP/GAAD/USS/AFP+USS/GAAD+USS vs MRI/CT for those who proceed to confirmatory imaging.
Rates of curative treatment [2 years]
Rates of curative treatment being offered (%) will be recorded on an intention to treat (ITT) basis from Multi-Disciplinary Team (MDT) meeting outcomes.
Rates of adherence [2 years]
• Attendance rates for biannual surveillance appointments (%), within predefined tolerance of 5-9 months post previous appointment.
Rates of discontinuation [2 years]
• Count (%) of surveillance discontinuation, defined as no visit >12 months.
Survival rates [7 years]
Long-term follow up data will be collected to determine rates of survival following HCC diagnosis at 1-year, 3-years and 5-years.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

• Patients with known liver cirrhosis referred into or already under hepatocellular carcinoma surveillance

Exclusion Criteria:

Pregnancy/breast-feeding.
Patients who do not have liver cirrhosis
Patients who already have hepatocellular carcinoma
Any patient who is unable to understand, retain and weigh information to make an informed decision, will be excluded from the study. The investigators will use every opportunity, including tele-interpretation services to minimise this from happening.