The SHUNT-V Study for Varices

HepQuant

Status: Completed

Conditions: Chronic Liver Disease

Treatments: Combination Product: HepQuant SHUNT Liver Diagnostic Test

Study type: Interventional

Funder types: Industry

Identifiers

NCT03583996

HQ-US-SHUNT-1801

Details and patient eligibility

About

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.

Full 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.

Enrollment: 306 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Diagnostic

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

---

306 participants in 1 patient group

Open Label

Experimental group

Description:

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.

Treatment:

Combination Product: HepQuant SHUNT Liver Diagnostic Test