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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Open Label | Experimental | 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| HepQuant SHUNT Liver Diagnostic Test | Combination Product | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Disease Severity Index (DSI) Less Than/Equal to 18.3 to Rule Out Large Varices | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| DSI and Probability of Large Esophageal Varices | Logistic regression analysis of DSI as predictor of large varices | 1 day |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Greg Everson, MD | HepQuant, LLC | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Arizona Liver Health | Chandler | Arizona | 85224 | United States | ||
| Southern CA Research Center |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 41586527 | Derived | Rahimi RS, Mena E, Lucas KJ, McRae MP, Kittelson J, Imperial JC, Smith AD, Everson GT; SHUNT-V Subjects, Investigators, and Coordinators. HMG-CoA Reductase Inhibitors (Statins) May Preserve Hepatic Function and Reduce Portal-Systemic Shunting in Compensated Advanced Chronic Liver Disease: Results From the SHUNT-V Study. Clin Transl Gastroenterol. 2026 Mar 1;17(3):e00980. doi: 10.14309/ctg.0000000000000980. | |
| 39523681 |
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A total of 306 subjects were enrolled in the study. For the analyses of all primary, secondary, and exploratory endpoints, only subjects who completed the HepQuant SHUNT Test and esophagogastroduodenoscopy (EGD) examination (N=280) were considered.
A total of 367 subjects were screened for the study.
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| ID | Title | Description |
|---|---|---|
| FG000 | Open Label | All subjects receive HepQuant SHUNT Liver Diagnostic Test within 42 days of the scheduled EGD. Test includes 20mg of 24-13C-cholic acid (13C cholate) mixed with Albumin via IV push, and 40mg of 2,2,4,4-D4-cholic acid (d4 cholate) mixed with juice orally, both doses given simultaneously one time. HepQuant SHUNT Liver Diagnostic Test: One time testing using the HepQuant SHUNT Liver Diagnostic Test kit (the combination product) in subjects with chronic liver disease (CLD) and undergoing a standard of care EGD. The SHUNT test was completed prior to the EGD. Each subject received an IV push dose of 13C Cholate mixed with Albumin simultaneously with an oral dose of d4 Cholate. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Oct 6, 2020 |
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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
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|
| Coronado |
| California |
| 92118 |
| United States |
| California Liver Research Institute | Pasadena | California | 91105 | United States |
| Inland Empire Liver Foundation | Rialto | California | 92377 | United States |
| Peak Gastroenterlogy Associates | Colorado Springs | Colorado | 80907 | United States |
| Nature Coast Clinical Research | Inverness | Florida | 34452 | United States |
| Mayo Clinic, Jacksonville | Jacksonville | Florida | 32224 | United States |
| Accel Research Sites | Orange City | Florida | 32763 | United States |
| Gastroenterology Associates of Pensacola | Pensacola | Florida | 32503 | United States |
| Gastroenterology Health Partners, PLLC | New Albany | Indiana | 47150 | United States |
| Tandem Clinical Research | Marrero | Louisiana | 70072 | United States |
| Digestive Disease Associates | Catonsville | Maryland | 21228 | United States |
| Mayo Clinic, Rochester | Rochester | Minnesota | 55905 | United States |
| St Louis University | St Louis | Missouri | 63104 | United States |
| Lucas Research (Diabetes & Endocrinology Consultants, PC) | Morehead City | North Carolina | 28557 | United States |
| PMG Research | Winston-Salem | North Carolina | 27103 | United States |
| Univ of Pennsylvania Hospital | Philadelphia | Pennsylvania | 19104 | United States |
| Ralph H Johnson Veterans Affairs Medical Center | Charleston | South Carolina | 29401 | United States |
| Methodist Dallas Liver Center | Dallas | Texas | 75203 | United States |
| Baylor, Scott & White | Dallas | Texas | 75246 | United States |
| Clinical Trials of Texas | San Antonio | Texas | 78229 | United States |
| Intermountain Healthcare | Murray | Utah | 84107 | United States |
| Bon Secours, Newport News | Newport News | Virginia | 23602 | United States |
| Bon Secours, Richmond | Richmond | Virginia | 23226 | United States |
| Gastroenterology Consultants of SW VA | Roanoke | Virginia | 24014 | United States |
| University of WA | Seattle | Washington | 98195 | United States |
| Derived |
| Shiffman M, Reddy KR, Leise MD, Qureshi K, Smith AD, Helmke S, Kittelson J, McRae MP, Imperial JC, Everson GT; SHUNT-V Investigators. Cholate Shunt, Oral Cholate Challenge and Endoscopic Lesions of Portal Hypertension: The SHUNT-V Study. Aliment Pharmacol Ther. 2025 Jan;61(1):75-87. doi: 10.1111/apt.18386. Epub 2024 Nov 10. |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. 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 was completed prior to the EGD. Each subject received an IV push dose of 13C Cholate mixed with Albumin simultaneously with an oral dose of d4 Cholate. |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Age at informed consent | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
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| Body Mass Index (BMI) | Incomplete data entry | Mean | Standard Deviation | kg/m^2 |
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| Child-Pugh Score | The Child-Pugh score predicts mortality in patients with cirrhosis. The scale represents the severity of cirrhosis in three classes: Child-Pugh A, 5 to 6 points (well-compensated disease); Child-Pugh B, 7 to 9 points (significant functional impairment); Child-Pugh C, 10 to 15 points (decompensated disease). | Incomplete data entry | Mean | Standard Deviation | units on a scale |
| |||||||||||||||
| MELD Score | The Model for End-Stage Liver Disease (MELD) score is a numerical scale that estimates the survival probability during the next three months in patients with end-stage liver disease based on international normalized ratio (INR), serum total bilirubin, and serum creatinine. The MELD score ranges from 6 to 40. Higher values correspond to higher mortality risk. | Incomplete data entry | Mean | Standard Deviation | units on a scale |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Disease Severity Index (DSI) Less Than/Equal to 18.3 to Rule Out Large Varices | 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. | Of the 280 subjects who completed the HepQuant SHUNT Test and EGD examination, 275 had both HepQuant SHUNT Test and EGD results. | Posted | Count of Participants | Participants | 1 day |
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| Secondary | DSI and Probability of Large Esophageal Varices | Logistic regression analysis of DSI as predictor of large varices | Of the 280 subjects who had the HepQuant SHUNT Test and EGD examination, 275 subjects had both HepQuant SHUNT Test and EGD. | Posted | Count of Participants | Participants | 1 day |
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Information regarding adverse events (AE) and/or serious adverse events (SAE) were recorded during Visit 2 (HepQuant SHUNT Test Administration, <=28 days after enrollment) and Visit 3 (Post-Test Follow-up, 2 to 30 days after Visit 2). AEs and SAEs related to the performance of the EGD were recorded (note: findings of the EGD were NOT recorded as AEs).
AEs/SAEs had their relationship to HepQuant SHUNT Liver Diagnostic Kit assessed by the clinician who examines and evaluates the participant based on temporal relationship and clinical judgment. Only 11 of the AEs below were related to HepQuant SHUNT test, and none of the intervention-related AEs were serious. Note: there were 297 subjects in the Safety Set which is different from the number of subjects that completed the study. All subjects in the Safety Set underwent the HepQuant SHUNT test.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. 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 was completed prior to the EGD. Each subject received an IV push dose of 13C Cholate mixed with Albumin simultaneously with an oral dose of d4 Cholate. | 1 | 297 | 5 | 297 | 40 | 297 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Coronary Artery Disease | Cardiac disorders | MedDRA 21.0 | Systematic Assessment | Moderate AE of coronary artery disease. The AE was an SAE and was considered unexpected and not related to the HepQuant SHUNT Liver Diagnostic Kit. The subject recovered from the AE but discontinued from the study because of the AE. |
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| Pleural Effusion | Respiratory, thoracic and mediastinal disorders | MedDRA 21.0 | Systematic Assessment | Severe AE of pleural effusion. The AE was an SAE and was considered expected and not related to the HepQuant SHUNT Liver Diagnostic Kit. The subject recovered from the AE but discontinued from the study because of the AE. |
|
| Peritonitis Bacterial | Infections and infestations | MedDRA 21.0 | Systematic Assessment | Severe AEs of peritonitis bacterial and septic shock. The AEs were considered SAEs and were considered expected and not related to the HepQuant SHUNT Liver Diagnostic Kit. The subject died and was discontinued from the study because of the AEs. |
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| Septic Shock | Infections and infestations | MedDRA 21.0 | Systematic Assessment | Severe AEs of peritonitis bacterial and septic shock. The AEs were considered SAEs and were considered expected and not related to the HepQuant SHUNT Liver Diagnostic Kit. The subject died and was discontinued from the study because of the AEs. |
|
| Hyperosmolar State | Metabolism and nutrition disorders | MedDRA 21.0 | Systematic Assessment | Moderate AE of hyperosmolar state. The AE of hyperosmolar state was an SAE and was considered unexpected and not related to the HepQuant SHUNT liver Diagnostic Kit. The subject recovered from the AE. |
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| Metabolic Encephalopathy | Nervous system disorders | MedDRA 21.0 | Systematic Assessment | Moderate AE of metabolic encephalopathy. The AE of metabolic encephalopathy was an SAE and considered unexpected and not related to the HepQuant SHUNT Liver Diagnostic Kit. The subject recovered from the AE. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Infusion site bruising | General disorders | MedDRA 21.0 | Systematic Assessment | Related to HepQuant SHUNT Liver Diagnostic Kit |
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| Catheter site bruise | General disorders | MedDRA 21.0 | Systematic Assessment | Related to HepQuant SHUNT Liver Diagnostic Kit |
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| Infusion site pain | General disorders | MedDRA 21.0 | Systematic Assessment | Related to HepQuant SHUNT Liver Diagnostic Kit |
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| Contusion | Injury, poisoning and procedural complications | MedDRA 21.0 | Systematic Assessment | One event in one affected subject was determined to be related to HepQuant SHUNT Liver Diagnostic Kit |
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| Abdominal pain upper | Gastrointestinal disorders | MedDRA 21.0 | Systematic Assessment | One event in one affected subject was determined to be related to HepQuant SHUNT Liver Diagnostic Kit |
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| Diarrhea | Gastrointestinal disorders | MedDRA 21.0 | Systematic Assessment | One event in one affected subject was determined to be related to HepQuant SHUNT Liver Diagnostic Kit |
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| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 21.0 | Systematic Assessment | Related to HepQuant SHUNT Liver Diagnostic Kit |
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| Flushing | Vascular disorders | MedDRA 21.0 | Systematic Assessment | Related to HepQuant SHUNT Liver Diagnostic Kit |
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| Fatigue | General disorders | MedDRA 21.0 | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA 21.0 | Systematic Assessment |
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| Vessel puncture site bruise | General disorders | MedDRA 21.0 | Systematic Assessment |
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| Fall | Injury, poisoning and procedural complications | MedDRA 21.0 | Systematic Assessment |
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| Hand fracture | Injury, poisoning and procedural complications | MedDRA 21.0 | Systematic Assessment |
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| Human bite | Injury, poisoning and procedural complications | MedDRA 21.0 | Systematic Assessment |
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| Post procedural discomfort | Injury, poisoning and procedural complications | MedDRA 21.0 | Systematic Assessment |
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| Road traffic accident | Injury, poisoning and procedural complications | MedDRA 21.0 | Systematic Assessment |
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| Thermal burn | Injury, poisoning and procedural complications | MedDRA 21.0 | Systematic Assessment |
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| Abdominal pain lower | Gastrointestinal disorders | MedDRA 21.0 | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | MedDRA 21.0 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 21.0 | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA 21.0 | Systematic Assessment |
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| Corona virus infection | Infections and infestations | MedDRA 21.0 | Systematic Assessment |
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| Gastroenteritis | Infections and infestations | MedDRA 21.0 | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA 21.0 | Systematic Assessment |
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| Otitis media acute | Infections and infestations | MedDRA 21.0 | Systematic Assessment |
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| Pneumonia streptococcal | Infections and infestations | MedDRA 21.0 | Systematic Assessment |
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| Urinary tract infection | Infections and infestations | MedDRA 21.0 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 21.0 | Systematic Assessment |
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| Hepatic encephalopathy | Nervous system disorders | MedDRA 21.0 | Systematic Assessment |
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| Acute respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA 21.0 | Systematic Assessment |
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| Haemoptysis | Respiratory, thoracic and mediastinal disorders | MedDRA 21.0 | Systematic Assessment |
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| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 21.0 | Systematic Assessment |
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| Diabetes mellitus inadequate control | Metabolism and nutrition disorders | MedDRA 21.0 | Systematic Assessment |
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| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 21.0 | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 21.0 | Systematic Assessment |
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| Confusional state | Psychiatric disorders | MedDRA 21.0 | Systematic Assessment |
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| Drug abuse | Psychiatric disorders | MedDRA 21.0 | Systematic Assessment |
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| Leukocytosis | Blood and lymphatic system disorders | MedDRA 21.0 | Systematic Assessment |
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| Ear pain | Ear and labyrinth disorders | MedDRA 21.0 | Systematic Assessment |
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| Eye pain | Eye disorders | MedDRA 21.0 | Systematic Assessment |
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| Food allergy | Immune system disorders | MedDRA 21.0 | Systematic Assessment |
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| Coronavirus test positive | Investigations | MedDRA 21.0 | Systematic Assessment |
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| Colon cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 21.0 | Systematic Assessment |
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| Acute kidney injury | Renal and urinary disorders | MedDRA 21.0 | Systematic Assessment |
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| Epididymal cyst | Reproductive system and breast disorders | MedDRA 21.0 | Systematic Assessment |
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| Urticaria | Skin and subcutaneous tissue disorders | MedDRA 21.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Elyse Handley | HepQuant LLC | 3037480524 | elyse.handley@hepquant.com |
| May 2, 2023 |
| Prot_SAP_000.pdf |
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| Black or African American |
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| Native Hawaiian or other Pacific Islander |
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| White |
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| Other |
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| No large varices and DSI <= 18.3 |
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The performance goal for validation of DSI <= 18.3 was the observed sensitivity must have been >0.85. The confidence level for the confidence interval (CI) was adjusted to maintain a 1-sided type I error rate of 0.025. |
| Sensitivity |
| 0.917 |
| 2-Sided |
| 95 |
| 0.775 |
| 0.982 |
| Other |
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