Clinical trial NCT03583996: The SHUNT-V Study for Varices
Official title: The HepQuant SHUNT Liver Diagnostic Kit for Likelihood of Large Esophageal Varices: The SHUNT-V Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Chronic Liver Disease
Lead sponsor: HepQuant, LLC
Sponsor class: INDUSTRY
First posted: 2018-07-12
Enrollment: 306
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: All subjects receive HepQuant SHUNT test and DSI measurement prior to a standard of care (SOC) EGD, to be done within 42 days of the SHUNT test. HepQuant SHUNT is a combination product where 24-13C-cholic acid (13C cholate) 20mg is administered intravenously once for each test and 2,2,4,4-D4-cholic acid (d4 cholate) 40mg is administered once orally for each test
Primary purpose: DIAGNOSTIC

Brief summary: 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: 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. The Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) Trial training dataset demonstrated that the DSI 18.3 had sensitivity 95%, specificity 54%, positive predictive value (PPV) 19%, negative predictive value (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, area under the receiver operating characteristic curve (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.

Eligibility criteria: 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 University of California, San Francisco (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

Primary outcomes:
measure: Disease Severity Index (DSI) Less Than/Equal to 18.3 to Rule Out Large Varices
timeFrame: 1 day
Secondary outcomes:
measure: DSI and Probability of Large Esophageal Varices
timeFrame: 1 day
Other outcomes:
Locations:
city: Chandler
country: United States
facility: Arizona Liver Health
state: Arizona
city: Coronado
country: United States
facility: Southern CA Research Center
state: California
city: Pasadena
country: United States
facility: California Liver Research Institute
state: California
city: Rialto
country: United States
facility: Inland Empire Liver Foundation
state: California
city: Colorado Springs
country: United States
facility: Peak Gastroenterlogy Associates
state: Colorado
city: Inverness
country: United States
facility: Nature Coast Clinical Research
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic, Jacksonville
state: Florida
city: Orange City
country: United States
facility: Accel Research Sites
state: Florida
city: Pensacola
country: United States
facility: Gastroenterology Associates of Pensacola
state: Florida
city: New Albany
country: United States
facility: Gastroenterology Health Partners, PLLC
state: Indiana
city: Marrero
country: United States
facility: Tandem Clinical Research
state: Louisiana
city: Catonsville
country: United States
facility: Digestive Disease Associates
state: Maryland
city: Rochester
country: United States
facility: Mayo Clinic, Rochester
state: Minnesota
city: Saint Louis
country: United States
facility: St Louis University
state: Missouri
city: Morehead City
country: United States
facility: Lucas Research (Diabetes & Endocrinology Consultants, PC)
state: North Carolina
city: Winston-Salem
country: United States
facility: PMG Research
state: North Carolina
city: Philadelphia
country: United States
facility: Univ of Pennsylvania Hospital
state: Pennsylvania
city: Charleston
country: United States
facility: Ralph H Johnson Veterans Affairs Medical Center
state: South Carolina
city: Dallas
country: United States
facility: Methodist Dallas Liver Center
state: Texas
city: Dallas
country: United States
facility: Baylor, Scott & White
state: Texas
city: San Antonio
country: United States
facility: Clinical Trials of Texas
state: Texas
city: Murray
country: United States
facility: Intermountain Healthcare
state: Utah
city: Newport News
country: United States
facility: Bon Secours, Newport News
state: Virginia
city: Richmond
country: United States
facility: Bon Secours, Richmond
state: Virginia
city: Roanoke
country: United States
facility: Gastroenterology Consultants of SW VA
state: Virginia
city: Seattle
country: United States
facility: University of WA
state: Washington
Study officials:
affiliation: HepQuant, LLC
name: Greg Everson, MD
role: STUDY_DIRECTOR
References: