The SHUNT-V Study for Varices

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

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.

Study Overview

• Status: Completed
• Conditions: Chronic Liver Disease
• Intervention / Treatment: Combination product: HepQuant SHUNT Liver Diagnostic Test

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 311
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Chandler, Arizona, United States, 85224
      • Arizona Liver Health
  • California
    • Coronado, California, United States, 92118
      • Southern CA Research Center
    • Pasadena, California, United States, 91105
      • California Liver Research Institute
    • Rialto, California, United States, 92377
      • Inland Empire Liver Foundation
  • Colorado
    • Colorado Springs, Colorado, United States, 80907
      • Peak Gastroenterlogy Associates
  • Florida
    • Inverness, Florida, United States, 34452
      • Nature Coast Clinical Research
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic, Jacksonville
    • Orange City, Florida, United States, 32763
      • Accel Research Sites
    • Pensacola, Florida, United States, 32503
      • Gastroenterology Associates of Pensacola
  • Indiana
    • New Albany, Indiana, United States, 47150
      • Gastroenterology Health Partners, PLLC
  • Louisiana
    • Marrero, Louisiana, United States, 70072
      • Tandem Clinical Research
  • Maryland
    • Catonsville, Maryland, United States, 21228
      • Digestive Disease Associates
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic, Rochester
  • Missouri
    • Saint Louis, Missouri, United States, 63104
      • St Louis University
  • North Carolina
    • Morehead City, North Carolina, United States, 28557
      • Lucas Research (Diabetes & Endocrinology Consultants, PC)
    • Winston-Salem, North Carolina, United States, 27103
      • PMG Research
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Univ of Pennsylvania Hospital
  • South Carolina
    • Charleston, South Carolina, United States, 29401
      • Ralph H Johnson Veterans Affairs Medical Center
  • Texas
    • Dallas, Texas, United States, 75203
      • Methodist Dallas Liver Center
    • Dallas, Texas, United States, 75246
      • Baylor, Scott & White
    • San Antonio, Texas, United States, 78229
      • Clinical Trials of Texas
  • Utah
    • Murray, Utah, United States, 84107
      • Intermountain Healthcare
  • Virginia
    • Newport News, Virginia, United States, 23602
      • Bon Secours, Newport News
    • Richmond, Virginia, United States, 23226
      • Bon Secours, Richmond
    • Roanoke, Virginia, United States, 24014
      • Gastroenterology Consultants of SW VA
  • Washington
    • Seattle, Washington, United States, 98195
      • University of WA

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: DIAGNOSTIC
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Open Label; 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; 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: HepQuant, LLC

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 23, 2019
• Primary Completion (ACTUAL): May 7, 2021
• Study Completion (ACTUAL): May 7, 2021

Study Registration Dates

• First Submitted: April 20, 2018
• First Submitted That Met QC Criteria: July 10, 2018
• First Posted (ACTUAL): July 12, 2018

Study Record Updates

• Last Update Posted (ACTUAL): August 30, 2021
• Last Update Submitted That Met QC Criteria: August 27, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases
• Other Study ID Numbers: HQ-US-SHUNT-1801

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: Yes
• product manufactured in and exported from the U.S.: No