The SHUNT-V Study for Varices

Study Overview
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Brief Summary
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The purpose of this study is to validate the Disease Severity Index (DSI) from the HepQuant SHUNT Liver Diagnostic Kit (Test) for likelihood of large esophageal varices.

Detailed Description
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The purpose of this study is to validate the Disease Severity Index (DSI) from the HepQuant SHUNT Liver Diagnostic Kit (Test) for likelihood of large esophageal varices. Our HALT-C Training dataset demonstrated that the DSI 18.3 had sensitivity 95%, specificity 54%, PPV 19%, NPV >99%, negative likelihood ratio (NLR) 0.09, and positive likelihood ratio (PLR) 2.09 for large varices. To validate DSI 18.3 as a cutoff for large varices, we will enroll 420 subjects with chronic liver disease (CLD) of mixed etiologies from 15 to 25 US clinical centers (CLD Validation dataset). The target prevalence of large varices is ≥20%. Each subject will have been scheduled for an esophago-gastro-duodenoscopy (EGD) as part of their standard of care for either variceal or non-variceal indications. Enrolled subjects will undergo standard clinical assessment, laboratory tests, and the HepQuant SHUNT Test. The EGD will be performed within 6 weeks following the HepQuant SHUNT Test. The relationship of DSI to large varices will be analyzed by univariate and multivariate logistic regression analyses, AUROC, and linear and nonlinear regression and correlation coefficients. Diagnostic performance of the DSI cutoff will be defined in the CLD Validation dataset and validated for likelihood of large esophageal varices. The validated DSI cutoff will identify subjects who are either unlikely or likely to have large esophageal varices.

Official Title
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The HepQuant SHUNT Liver Diagnostic Kit for Likelihood of Large Esophageal Varices: The SHUNT-V Study

Conditions
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Chronic Liver Disease

Intervention / Treatment
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* Combination Product: HepQuant SHUNT Liver Diagnostic Test


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ability to have a peripheral venous catheter for administration of the 13C cholate Ability to take the oral dose of d4-cholate Ability to hold morning doses of medications for the 90-minute duration of the HepQuant SHUNT Test Meets the protocol defined criteria for CLD in addition to having the diagnoses of CLD for >6 months Is scheduled, or in the process of being scheduled, for a standard of care EGD Exclusion Criteria: Unable to give informed consent Unable to obtain venous access for administration of intravenous cholate Unable to absorb orally-administered cholate Known hypersensitivity to human serum albumin Known hypersensitivity to any of the components of the HepQuant SHUNT Liver Diagnostic Kit Acute hepatitis or Acute Liver Failure Acute drug-induced liver disease (DILI) Noncirrhotic causes for portal hypertension and varices Ongoing active alcoholic hepatitis Child-Pugh class C defined by Child-Pugh score 10 or higher Dialysis Active infection or febrile illness within the last month Documented history of esophageal or gastric variceal hemorrhage Documented history of treatment of esophageal varices Documented history of endoscopic findings of large esophageal varices Hepatocellular carcinoma beyond Milan or UCSF criteria Thrombosis of main portal vein Liver transplant recipient Pregnancy Women who are breast-feeding Serious intercurrent medical or surgical illness, such as acute myocardial infarction, acute cerebral hemorrhage, sepsis, or other immediate life-threatening illness

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Interventional Model Description: All subjects receive HepQuant SHUNT test and DSI measurement prior to a SOC EGD, to be done within 42 days of the SHUNT test. HepQuant SHUNT is a combination product where 13C Cholate 20mg is administered intravenously once for each test and d4 Cholate 40mg is administered once orally for each test
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Open Label<br>All subjects receive HepQuant SHUNT Liver Diagnostic Test within 42 days of the scheduled EGD. Test includes 20mg of 13C Cholate mixed with Albumin via IV push, and 40mg of d4 Cholate mixed with juice orally, both doses given simultaneously one time. | Combination Product: HepQuant SHUNT Liver Diagnostic Test<br>* One time testing using the HepQuant SHUNT Liver Diagnostic Test kit (the combination product) in subjects with CLD and undergoing a standard of care EGD. The SHUNT test will be completed prior to the EGD. Each subject will receive an IV push dose of 13C Cholate mixed with Albumin simultaneously with an oral dose of d4 Cholate<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| DSI less than/equal to 18.3 | The primary objective of this study is to measure the subjects' liver function using DSI ≤18.3 for those that are not likely to have large esophageal varices. | 1 day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| DSI greater than 18.3 | Secondary objective is to measure the subjects' liver function using DSI >18.3 for those subjects who are likely to have large esophageal varices. | 1 day |