Correlation and Comparison of the HepQuant® Disease Severity Index (DSI) With Hepatic Venous Pressure Gradient (HVPG)

• Sponsor: University of Colorado, Denver (Other)
• Overall Status: Completed
• CT.gov ID: NCT02523196
• Collaborator: (none)
• Enrollment: 20
• Location: 1
• Arm: 1
• Duration (Months): 11.8
• Patients Per Site Per Month: 1.7

Study Details

Study Description

Brief Summary

This study plans to learn more about a new test to look at liver function, the HepQuant-Shunt (HQ-Shunt). The HQ-Shunt is being evaluated for safety and effectiveness as an alternative to Hepatic Venous Pressure Gradient testing in patients with liver disease.

Condition or Disease	Intervention/Treatment	Phase
Liver Disease	Drug: HepQuant-SHUNT (Drug and Device) #65,123 (4D-cholate) and IND #65,121 (13C-cholate); Device: Hepatic Venous Pressure Gradient (HVPG)	Phase 3

Detailed Description

The goal of this study is to demonstrate the HQ-SHUNT is safe, simple to administer, noninvasive, cost-effective, and well tolerated by patients. This study will compare the HQ-SHUNT to Hepatic Venous Pressure Gradient (HVPG) testing. In this study, 100 consecutive patients with various etiologies of liver disease who have undergone technically successful HVPG testing as standard of care will also undergo HQ-SHUNT testing.

Study Design

• Study Type: Interventional
• Actual Enrollment: 20 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: Correlation and Comparison of the HepQuant® Disease Severity Index (DSI) With Hepatic Venous Pressure Gradient (HVPG)
• Study Start Date: Mar 1, 2016
• Actual Primary Completion Date: Feb 23, 2017
• Actual Study Completion Date: Feb 23, 2017

Arms and Interventions

Arm

Intervention/Treatment

Other: (HVPG) and HepQuant-SHUNT (HQ-Shunt) Successful Hepatic Venous Pressure Gradiant (HVPG) testing is required prior to administration of the HepQuant-SHUNT test. Comparison of Disease Severity Index (DSI) from HQ-SHUNT with HVPG in identifying patients with cirrhosis and patients with varices.

Drug: HepQuant-SHUNT (Drug and Device) #65,123 (4D-cholate) and IND #65,121 (13C-cholate); The HQ-SHUNT test is being evaluated for safety and effectiveness as an alternative to Hepatic Venous Pressure Gradient (HVPG) testing in patients with liver disease; Other Names: HQ-SHUNT ; Device: Hepatic Venous Pressure Gradient (HVPG); Hepatic Venous Pressure Gradient (HVPG) is a test for patients with liver disease; Other Names: (HVPG)

Outcome Measures

Primary Outcome Measures

1. Results of HepQuant SHUNT Test: Elimination Rate (IV Phase 1 Only; Min-1) [Up to 90 minutes]

   Compare Disease Severity Index (DSI) from HQ-SHUNT for defining patients with (HVPG ≥6 mmHg) and without (HVPG <6 mmHg) portal hypertension.

2. Results of HepQuant SHUNT Test: Systemic Clearance [Up to 90 minutes]

   Compare Disease Severity Index (DSI) from HQ-SHUNT for defining patients with (HVPG ≥6 mmHg) and without (HVPG <6 mmHg) portal hypertension. Systemic Clearance (13C-CA; ml min-1)

3. Results of HepQuant SHUNT Test: Apparent Portal Clearance [Up to 90 minutes]

   Compare Disease Severity Index (DSI) from HQ-SHUNT for defining patients with (HVPG ≥6 mmHg) and without (HVPG <6 mmHg) portal hypertension.

4. Results of HepQuant SHUNT Test: Systemic Hepatic Filtration Rate [Up to 90 minutes]

   Compare Disease Severity Index (DSI) from HQ-SHUNT for defining patients with (HVPG ≥6 mmHg) and without (HVPG <6 mmHg) portal hypertension.

5. Results of HepQuant SHUNT Test: Portal Hepatic Filtration Rate [Up to 90 minutes]

   Compare Disease Severity Index (DSI) from HQ-SHUNT for defining patients with (HVPG ≥6 mmHg) and without (HVPG <6 mmHg) portal hypertension.

6. Results of HepQuant SHUNT Test: SHUNT [Up to 90 minutes]

   Compare Disease Severity Index (DSI) from HQ-SHUNT for defining patients with (HVPG ≥6 mmHg) and without (HVPG <6 mmHg) portal hypertension. SHUNT% is The percent of the oral dose of cholate that escapes hepatic extraction

7. Results of HepQuant SHUNT Test: DSI Score [Up to 90 minutes]

   Compare Disease Severity Index (DSI) from HQ-SHUNT for defining patients with (HVPG ≥6 mmHg) and without (HVPG <6 mmHg) portal hypertension. DSI range is from 0 to 50. 0 implies no disease; 50 implies severe end-stage disease.

8. Results of HepQuant SHUNT Test: STAT [60 minutes]

   Compare HepQuant STAT test from HQ-SHUNT for defining patients with (HVPG ≥6 mmHg) and without (HVPG <6 mmHg) portal hypertension. HepQuant STAT is a simple "drink and draw" blood-based clearance test that quantifies hepatic impairment from early through late stages of disease.

Secondary Outcome Measures

1. Survey Patients on Their Experience of Having Both HQ-SHUNT and HVPG Procedures. [Immediately post HepQuant SHUNT test (Baseline up to Day 60)]

   Overall experience and willingness to repeat 0-10 Scale 0 being no pain, 10 being severe pain 0 being no discomfort, 10 being severe discomfort 0 being no interference with daily life, 10 being unable to carry on activities 0 being very negative experience, 10 being very positive experience 0 being definitely not wanting to have the test again, 10 being very willing to have the test again

2. Hours for Test [Baseline, up to Day 60]

   Number of hours it took for subjects to complete each test

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Liver disease patient scheduled to have an Hepatic Venous Pressure Gradient (HVPG) procedure

• At time of enrollment, being between the ages of 18 and 75

Exclusion Criteria:

• Concomitant treatment with both a beta blocker and an ACE inhibitor

• Concurrent hepatic malignancy. Patients with a history of treated HCC can be included if there is no evidence of recurrent disease at the time of this study.

• Unstable angina or history of myocardial infarction or congestive heart failure within 6 months prior to enrollment into this study

• Renal insufficiency with chronic kidney disease stage 4 or 5 (GFR < 30 mL/min/1.73m2)

• Crohn's disease or any active intestinal inflammatory condition

• Having had an ileal resection

• Diabetic Gastroparesis

• Pregnancy or intent to become pregnant. Urine pregnancy tests will be performed prior to HQ SHUNT testing.

• Inability to consent for one's self

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Colorado Denver (Leprino Building)	Aurora	Colorado	United States	80045

Sponsors and Collaborators

• University of Colorado, Denver

Investigators

• Principal Investigator: Amanda Wieland, MD, University of Colorado, Denver

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Aug 17, 2015
• Informed Consent Form - Jun 30, 2017

More Information

Publications

None provided.

• Responsible Party: University of Colorado, Denver
• ClinicalTrials.gov Identifier: NCT02523196
• Other Study ID Numbers: 15-0520; UL1TR001082
• First Posted: Aug 14, 2015
• Last Update Posted: Aug 9, 2021
• Last Verified: Aug 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by University of Colorado, Denver: Hepatic Venous Pressure Gradient (HVPG) testing; HepQuant-SHUNT; Liver Function
• Additional relevant MeSH terms: Liver Diseases; Cholic Acids

Study Results

Participant Flow

Pre-assignment Detail	Subjects can be excluded if they do not complete the study visit within 60 days of the HVPG testing or if they test positive in a urine pregnancy test the day of the HQ-SHUNT test.

Arm/Group Title	Hepatic Venous Pressure Gradient (HVPG) and HepQuant-SHUNT (HQ
Arm/Group Description	Comparison of Disease Severity Index (DSI) from HQ-SHUNT with HVPG in identifying patients with cirrhosis and patients with varices. Successful Hepatic Venous Pressure Gradiant (HVPG) testing is required prior to administration of the HepQuant-SHUNT test. Hepatic Venous Pressure Gradient (HVPG): Hepatic Venous Pressure Gradient (HVPG) is a test for patients with liver disease HepQuant-SHUNT: The HQ-SHUNT test is being evaluated for safety and effectiveness as an alternative to Hepatic Venous Pressure Gradient (HVPG) testing in patients with liver disease
Period Title: Overall Study
STARTED	20
Received HVPG	20
Received HQ Shunt	20
COMPLETED	20
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	HepQuant-SHUNT (HQ-Shunt)
Arm/Group Description	Comparison of Disease Severity Index (DSI) from HQ-SHUNT with HVPG in identifying patients with cirrhosis and patients with varices. HepQuant-SHUNT: The HQ-SHUNT test is being evaluated for safety and effectiveness as an alternative to Hepatic Venous Pressure Gradient (HVPG) testing in patients with liver disease
Overall Participants	20
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	49.8 (10.1)
Sex: Female, Male (Count of Participants)
Female	15 75%
Male	5 25%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	6 30%
Not Hispanic or Latino	14 70%
Unknown or Not Reported	0 0%
Race/Ethnicity, Customized (Count of Participants)
White	20 100%
Non-Wihite	0 0%
Weight (Kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Kg]	87.1 (19.7)
Etiology of Liver Disease (Count of Participants)
NASH	9 45%
HCV	4 20%
Autoimmune Hepatitis	3 15%
Wilsons Disease	1 5%
Budd-Chiari Syndrome	1 5%
Cryptogenic	1 5%
Other	1 5%
Fibrosis Stage (Count of Participants)
F0	2 10%
F1	6 30%
F2-F3 (F2.5)	3 15%
F3	3 15%
F4	5 25%
NA	1 5%
Steatosis Grade (Count of Participants)
Mild, <5%	4 20%
Mild, 5 to 33%	9 45%
Moderate, 33 to 66%	4 20%
Severe, >66%	1 5%
NA	2 10%
Co-Morbid Conditions (participants) [Number]
Obesity	10 50%
Diabetes Mellitus	9 45%
Hypertension	8 40%
Dyslipidemia	4 20%
Gout	1 5%
Extrahepatic autoimmune disease	7 35%
Pulmonary hypertension	1 5%
Malignancy	1 5%
Standard Laboratory Tests: Serum Sodium (mEq/L) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mEq/L]	136 (4)
Standard Laboratory Tests: Creatine, Glucose and Bilirubin (mg/dL) [Mean (Standard Deviation) ]
Creatine	0.71 (0.15)
Glucose	149 (140)
Bilirubin	0.75 (0.34)
Standard Laboratory Tests: AST, Alkaline Phosphatase, ALT (IU/L) [Mean (Standard Deviation) ]
AST	46 (36)
Alkaline Phosphatase	108 (100)
ALT	53 (45)
Standard Laboratory Tests: Albumin (g/L) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [g/L]	3.79 (.49)
Standard Laboratory Tests: WBC, RBC and Platelets (count/nL) [Mean (Standard Deviation) ]
WBC	7.22 (3.06)
RBC	4.44 (0.84)
Platelets	218.45 (102.56)
Standard Laboratory Tests: Hemoglobin (g/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [g/dL]	13.38 (2.91)
Standard Laboratory Tests: Hematocrit (%) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [%]	39.60 (7.50)
Standard Laboratory Tests: INR (No units (ratio)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [No units (ratio)]	1.11 (0.14)
Standard Laboratory Tests: MELD Score (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	7.35 (1.84)
Standard Laboratory Tests: Child-Turcotte-Pugh (CTP) Score (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	5.35 (0.59)

Outcome Measures

1. Primary Outcome

Title	Results of HepQuant SHUNT Test: Elimination Rate (IV Phase 1 Only; Min-1)
Description	Compare Disease Severity Index (DSI) from HQ-SHUNT for defining patients with (HVPG ≥6 mmHg) and without (HVPG <6 mmHg) portal hypertension.
Time Frame	Up to 90 minutes

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	HVPG <6 mmHg	HVPG ≥6 mmHg	All Patients
Arm/Group Description	Patients without portal hypertension	Patients with portal hypertension	patients with (HVPG ≥6 mmHg) and without (HVPG <6 mmHg) portal hypertension
Measure Participants	11	9	20
Mean (Standard Deviation) [min-1]	0.104 (0.017)	0.092 (0.023)	0.099 (0.020)

2. Primary Outcome

Title	Results of HepQuant SHUNT Test: Systemic Clearance
Description	Compare Disease Severity Index (DSI) from HQ-SHUNT for defining patients with (HVPG ≥6 mmHg) and without (HVPG <6 mmHg) portal hypertension. Systemic Clearance (13C-CA; ml min-1)
Time Frame	Up to 90 minutes

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	HVPG <6 mmHg	HVPG ≥6 mmHg	All Patients
Arm/Group Description	Patients without portal hypertension	Patients with portal hypertension	patients with (HVPG ≥6 mmHg) and without (HVPG <6 mmHg) portal hypertension
Measure Participants	11	9	20
Mean (Standard Deviation) [(13C-CA; ml min-1)]	463 (161)	384 (137)	427 (152)

3. Primary Outcome

Title	Results of HepQuant SHUNT Test: Apparent Portal Clearance
Description	Compare Disease Severity Index (DSI) from HQ-SHUNT for defining patients with (HVPG ≥6 mmHg) and without (HVPG <6 mmHg) portal hypertension.
Time Frame	Up to 90 minutes

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	HVPG <6 mmHg	HVPG ≥6 mmHg	All Patients
Arm/Group Description	Patients without portal hypertension	Patients with portal hypertension	patients with (HVPG ≥6 mmHg) and without (HVPG <6 mmHg) portal hypertension
Measure Participants	11	9	20
Mean (Standard Deviation) [d4-CA; ml min-1]	1538 (525)	975 (464)	1285 (564)

4. Primary Outcome

Title	Results of HepQuant SHUNT Test: Systemic Hepatic Filtration Rate
Description	Compare Disease Severity Index (DSI) from HQ-SHUNT for defining patients with (HVPG ≥6 mmHg) and without (HVPG <6 mmHg) portal hypertension.
Time Frame	Up to 90 minutes

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	HVPG <6 mmHg	HVPG ≥6 mmHg	All Patients
Arm/Group Description	Patients without portal hypertension	Patients with portal hypertension	patients with (HVPG ≥6 mmHg) and without (HVPG <6 mmHg) portal hypertension
Measure Participants	11	9	20
Mean (Standard Deviation) [ml min-1 kg-1]	5.30 (1.09)	4.47 (1.43)	4.92 (1.29)

5. Primary Outcome

Title	Results of HepQuant SHUNT Test: Portal Hepatic Filtration Rate
Description	Compare Disease Severity Index (DSI) from HQ-SHUNT for defining patients with (HVPG ≥6 mmHg) and without (HVPG <6 mmHg) portal hypertension.
Time Frame	Up to 90 minutes

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	HVPG <6 mmHg	HVPG ≥6 mmHg	All Patients
Arm/Group Description	Patients without portal hypertension	Patients with portal hypertension	patients with (HVPG ≥6 mmHg) and without (HVPG <6 mmHg) portal hypertension
Measure Participants	11	9	20
Mean (Standard Deviation) [ml min-1 kg-1]	17.83 (6.37)	11.11 (5.24)	14.81 (6.69)

6. Primary Outcome

Title	Results of HepQuant SHUNT Test: SHUNT
Description	Compare Disease Severity Index (DSI) from HQ-SHUNT for defining patients with (HVPG ≥6 mmHg) and without (HVPG <6 mmHg) portal hypertension. SHUNT% is The percent of the oral dose of cholate that escapes hepatic extraction
Time Frame	Up to 90 minutes

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	HVPG <6 mmHg	HVPG ≥6 mmHg	All Patients
Arm/Group Description	Patients without portal hypertension	Patients with portal hypertension	patients with (HVPG ≥6 mmHg) and without (HVPG <6 mmHg) portal hypertension
Measure Participants	11	9	20
Mean (Standard Deviation) [percentage]	29.08 (9.89)	47.50 (24.24)	37.37 (19.68)

7. Primary Outcome

Title	Results of HepQuant SHUNT Test: DSI Score
Description	Compare Disease Severity Index (DSI) from HQ-SHUNT for defining patients with (HVPG ≥6 mmHg) and without (HVPG <6 mmHg) portal hypertension. DSI range is from 0 to 50. 0 implies no disease; 50 implies severe end-stage disease.
Time Frame	Up to 90 minutes

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	HVPG <6 mmHg	HVPG ≥6 mmHg	All Patients
Arm/Group Description	Patients without portal hypertension	Patients with portal hypertension	patients with (HVPG ≥6 mmHg) and without (HVPG <6 mmHg) portal hypertension
Measure Participants	11	9	20
Mean (Standard Deviation) [score on a scale (DSI Score)]	14.64 (3.86)	20.68 (6.30)	17.36 (5.84)

8. Secondary Outcome

Title	Survey Patients on Their Experience of Having Both HQ-SHUNT and HVPG Procedures.
Description	Overall experience and willingness to repeat 0-10 Scale 0 being no pain, 10 being severe pain 0 being no discomfort, 10 being severe discomfort 0 being no interference with daily life, 10 being unable to carry on activities 0 being very negative experience, 10 being very positive experience 0 being definitely not wanting to have the test again, 10 being very willing to have the test again
Time Frame	Immediately post HepQuant SHUNT test (Baseline up to Day 60)

Outcome Measure Data

Analysis Population Description

subjects that underwent HVPG and HQ-Shunt completed surveys

Arm/Group Title	Hepatic Venous Pressure Gradient (HVPG)	HepQuant-SHUNT (HQ-Shunt)
Arm/Group Description	Successful Hepatic Venous Pressure Gradiant (HVPG) testing is required prior to administration of the HepQuant-SHUNT test. Hepatic Venous Pressure Gradient (HVPG): Hepatic Venous Pressure Gradient (HVPG) is a test for patients with liver disease	Comparison of Disease Severity Index (DSI) from HQ-SHUNT with HVPG in identifying patients with cirrhosis and patients with varices. HepQuant-SHUNT: The HQ-SHUNT test is being evaluated for safety and effectiveness as an alternative to Hepatic Venous Pressure Gradient (HVPG) testing in patients with liver disease
Measure Participants	20	20
Pain	3.9 (3.14)	.35 (.59)
Discomfort	4.2 (2.89)	.5 (.89)
Interfere with Daily Life	5.9 (3.14)	1.25 (1.41)
Overall Experience	6.2 (2.73)	9.6 (.68)
Willingness to Repeat	5.65 (3.59)	9.85 (.37)

9. Secondary Outcome

Title	Hours for Test
Description	Number of hours it took for subjects to complete each test
Time Frame	Baseline, up to Day 60

Outcome Measure Data

Analysis Population Description

Number of hours

Arm/Group Title	Hepatic Venous Pressure Gradient (HVPG)	HepQuant-SHUNT (HQ-Shunt)
Arm/Group Description	Successful Hepatic Venous Pressure Gradiant (HVPG) testing is required prior to administration of the HepQuant-SHUNT test. Hepatic Venous Pressure Gradient (HVPG): Hepatic Venous Pressure Gradient (HVPG) is a test for patients with liver disease	Comparison of Disease Severity Index (DSI) from HQ-SHUNT with HVPG in identifying patients with cirrhosis and patients with varices. HepQuant-SHUNT: The HQ-SHUNT test is being evaluated for safety and effectiveness as an alternative to Hepatic Venous Pressure Gradient (HVPG) testing in patients with liver disease
Measure Participants	20	20
0-3 hours	4 20%	18 NaN
3-6 hours	5 25%	2 NaN
6-9 hours	3 15%	0 NaN
9-12 hours	8 40%	0 NaN

10. Primary Outcome

Title	Results of HepQuant SHUNT Test: STAT
Description	Compare HepQuant STAT test from HQ-SHUNT for defining patients with (HVPG ≥6 mmHg) and without (HVPG <6 mmHg) portal hypertension. HepQuant STAT is a simple "drink and draw" blood-based clearance test that quantifies hepatic impairment from early through late stages of disease.
Time Frame	60 minutes

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	HVPG <6 mmHg	HVPG ≥6 mmHg	All Patients
Arm/Group Description	Patients without portal hypertension	Patients with portal hypertension	patients with (HVPG ≥6 mmHg) and without (HVPG <6 mmHg) portal hypertension
Measure Participants	11	9	20
Mean (Standard Deviation) [uM/min]	0.61 (0.27)	1.29 (0.73)	0.92 (0.62)

Adverse Events

Time Frame	6 Weeks
Adverse Event Reporting Description	no adverse events
Arm/Group Title	Hepatic Venous Pressure Gradient (HVPG)		HepQuant-SHUNT (HQ-Shunt)
Arm/Group Description	Successful Hepatic Venous Pressure Gradiant (HVPG) testing is required prior to administration of the HepQuant-SHUNT test. Hepatic Venous Pressure Gradient (HVPG): Hepatic Venous Pressure Gradient (HVPG) is a test for patients with liver disease		Comparison of Disease Severity Index (DSI) from HQ-SHUNT with HVPG in identifying patients with cirrhosis and patients with varices. HepQuant-SHUNT: The HQ-SHUNT test is being evaluated for safety and effectiveness as an alternative to Hepatic Venous Pressure Gradient (HVPG) testing in patients with liver disease
All Cause Mortality
	Hepatic Venous Pressure Gradient (HVPG)		HepQuant-SHUNT (HQ-Shunt)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/20 (0%)		0/20 (0%)
Serious Adverse Events
	Hepatic Venous Pressure Gradient (HVPG)		HepQuant-SHUNT (HQ-Shunt)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/20 (0%)		0/20 (0%)
Other (Not Including Serious) Adverse Events
	Hepatic Venous Pressure Gradient (HVPG)		HepQuant-SHUNT (HQ-Shunt)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/20 (0%)		0/20 (0%)

Limitations/Caveats

Study did not reach enrollment goal of 110, therefore analysis was limited due to low power

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.