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Surrogate Markers of Portal Pressure

Primary Purpose

Portal Hypertension, Cirrhosis

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
HVPG
Indocyanine Green Retention test
Liver stiffness measurement
Spleen stiffness measurement
Sponsored by
VA Connecticut Healthcare System
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Portal Hypertension focused on measuring ICG, ARFI, portal hypertension, cirrhosis, diagnostic study

Eligibility Criteria

18 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Age 18-85
  • HCV infection (HCV-RNA positive)
  • Compensated cirrhosis will be defined histologically and/or clinically (presence of compatible lab findings (platelet count ≤ 150,000, total bilirubin ≥ 2, serum albumin ≤ 3.5, INR ≥ 1.2) PLUS compatible physical exam features (cutaneous stigmata, gynecomastia in men, or splenomegaly) OR compatible radiological findings (nodular liver surface, splenomegaly, and/or collaterals). (The ultimate confirmation of the diagnosis of cirrhosis will be a baseline HVPG > 5 mmHg)
  • Planned anti-HCV therapy in the next 3 months

Exclusion Criteria:

  • Any clinically-evident complication of cirrhosis that defines decompensation : jaundice, ascites, variceal hemorrhage, overt hepatic encephalopathy)
  • Hepatocellular carcinoma
  • Co-infection with HBV or HIV
  • Ongoing alcohol abuse
  • Occlusive portal thrombosis,
  • Presence of comorbid conditions conferring a life expectancy<1 year, history of allergy to iodides, pregnancy

Sites / Locations

  • Yale-New Haven Hospital
  • VA Connecticut Healthcare System

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Active Comparator

Active Comparator

Arm Label

Indocyanine green retention test

Liver stiffness measurement

Spleen stiffness measurement

Arm Description

A baseline venous sample of 5 ml of venous will be drawn for pre-infusion measurement. Under sterile conditions 0.5 mg/kg body weight of ICG will be injected into vein. Further blood samples (5 ml each) will be collected at 5, 10, 15 and 20 minute intervals after the injection from a peripheral vein in the opposite arm using another intravenous catheter. After serum is separated by centrifugation, optical densities will be measured at 804 nm using a calibrated method for measurement of ICG level s. ICG retention at 15 minutes and elimination rate constant will be calculated by fitting the serum disappearance curve to a single exponential decay equation.This will be compared to portal pressure measured by Hepatic Venous Portal Gradient (HVPG).

ARFI measurements of the liver will be obtained using a standard ultrasound probe. The patient will be lying on his back and will be asked to hold his/her breath for 2-5 seconds during measurements.These will be compared to portal pressure measured by Hepatic Venous Portal Gradient (HVPG).

ARFI measurements of the spleen will be obtained using a standard ultrasound probe. The patient will be lying on his back and will be asked to hold his/her breath for 2-5 seconds during measurements.These will be compared to portal pressure measured by Hepatic Venous Portal Gradient (HVPG).

Outcomes

Primary Outcome Measures

Indocyanine Green before and after treatment of hepatitis c
Indocyanine Green will be obtained , this will be conducted before and after treatment for hepatitis c and is measured in mg/dl

Secondary Outcome Measures

Spleen stiffness before and after treatment of hepatitis c
Spleen stiffness will be obtained by ARFI, this will be conducted before and after treatment for hepatitis c and is measured in m/sec
Liver stiffness before and after treatment of hepatitis c
Liver stiffness will be obtained by ARFI, this will be conducted before and after treatment for hepatitis c and is measured in m/sec
Hepatic venous pressure gradient before and after treatment of hepatitis c
Hepatic venous pressure gradient would be obtained by catheterization of the hepatic vein, this will be conducted before and after treatment for hepatitis c and is measured in mmHg

Full Information

First Posted
January 9, 2015
Last Updated
November 22, 2019
Sponsor
VA Connecticut Healthcare System
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1. Study Identification

Unique Protocol Identification Number
NCT02508298
Brief Title
Surrogate Markers of Portal Pressure
Official Title
Surrogate Markers of Portal Pressure and Changes in Portal Pressure in Patients With Compensated Cirrhosis Undergoing Anti-viral Therapy
Study Type
Interventional

2. Study Status

Record Verification Date
November 2019
Overall Recruitment Status
Completed
Study Start Date
April 2014 (undefined)
Primary Completion Date
July 2018 (Actual)
Study Completion Date
July 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
VA Connecticut Healthcare System

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
This is a prospective longitudinal study that will evaluate if changes (pre and post therapy) in indocyanine green (ICG) retention test and liver stiff ness (LS) and spleen stiffness (SS) as measured by acoustic radiofrequency impulse (ARFI) correlate with changes in portal pressure as determined by the hepatic vein pressure gradient (HVPG) in patients with compensated hepatitis C virus (HCV) cirrhosis undergoing antiviral therapy.
Detailed Description
Subjects will be recruited from the outpatient setting of the West Haven VA Medical Center and the Yale Liver Clinic. Subjects between 18-85 years of age with compensated cirrhosis due to chronic hepatitis C virus (HCV) infection who will be starting anti-viral therapy to treat HCV within the next 3 months will be eligible for this study. 33 subjects (assuming 10% loss to follow-up) will be recruited and their participation will last from 6-12 months. The expected duration of the study is 2 years. The primary end point of the study is to correlate the change (from baseline to after completing anti-HCV therapy) in ICG retention test, LS and SS as measured by ARFI with HVPG. After consent has been obtained, subjects will undergo ICG retention test, ARFI imaging and HVPG measurements before and after HCV therapy. Blood samples, demographic and clinical data will be collected before and after HCV therapy. Correlations between changes in HVPG and changes in ICG, LS and SS will be assessed. With 30 patients , we will have 80% power to perform a hypothesis test of the Pearson correlation assuming an observed correlation of 0.70 and a two-sided type I error rate of 0.05.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Portal Hypertension, Cirrhosis
Keywords
ICG, ARFI, portal hypertension, cirrhosis, diagnostic study

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
41 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Indocyanine green retention test
Arm Type
Active Comparator
Arm Description
A baseline venous sample of 5 ml of venous will be drawn for pre-infusion measurement. Under sterile conditions 0.5 mg/kg body weight of ICG will be injected into vein. Further blood samples (5 ml each) will be collected at 5, 10, 15 and 20 minute intervals after the injection from a peripheral vein in the opposite arm using another intravenous catheter. After serum is separated by centrifugation, optical densities will be measured at 804 nm using a calibrated method for measurement of ICG level s. ICG retention at 15 minutes and elimination rate constant will be calculated by fitting the serum disappearance curve to a single exponential decay equation.This will be compared to portal pressure measured by Hepatic Venous Portal Gradient (HVPG).
Arm Title
Liver stiffness measurement
Arm Type
Active Comparator
Arm Description
ARFI measurements of the liver will be obtained using a standard ultrasound probe. The patient will be lying on his back and will be asked to hold his/her breath for 2-5 seconds during measurements.These will be compared to portal pressure measured by Hepatic Venous Portal Gradient (HVPG).
Arm Title
Spleen stiffness measurement
Arm Type
Active Comparator
Arm Description
ARFI measurements of the spleen will be obtained using a standard ultrasound probe. The patient will be lying on his back and will be asked to hold his/her breath for 2-5 seconds during measurements.These will be compared to portal pressure measured by Hepatic Venous Portal Gradient (HVPG).
Intervention Type
Procedure
Intervention Name(s)
HVPG
Other Intervention Name(s)
Hepatic Venous Portal Gradient
Intervention Description
HVPG will be performed by placing a placing a 7F venous catheter into a supra-hepatic vein and then advancing a 5F balloon-tipped catheter into the right hepatic vein. Wedged hepatic venous pressure (WHVP) and free hepatic venous pressure (FHVP) will be measured by connection to an external transducer and polygraph (PowerLab, ADInstruments Inc., Colorado Springs, CO). After inflating the balloon catheter, adequacy of the occlusion will be established by injection of a small amount of radiologic contrast medium. Hepatic Venous Pressure gradient (HVPG) will be calculated as the difference between WHVP and FHVP.
Intervention Type
Drug
Intervention Name(s)
Indocyanine Green Retention test
Other Intervention Name(s)
ICG test
Intervention Description
As decribed in arm descriptions
Intervention Type
Device
Intervention Name(s)
Liver stiffness measurement
Other Intervention Name(s)
LS
Intervention Description
As decribed in arm descriptions; perfromed by ARFI
Intervention Type
Device
Intervention Name(s)
Spleen stiffness measurement
Other Intervention Name(s)
SS
Intervention Description
As decribed in arm descriptions; performed by ARFI
Primary Outcome Measure Information:
Title
Indocyanine Green before and after treatment of hepatitis c
Description
Indocyanine Green will be obtained , this will be conducted before and after treatment for hepatitis c and is measured in mg/dl
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Spleen stiffness before and after treatment of hepatitis c
Description
Spleen stiffness will be obtained by ARFI, this will be conducted before and after treatment for hepatitis c and is measured in m/sec
Time Frame
2 years
Title
Liver stiffness before and after treatment of hepatitis c
Description
Liver stiffness will be obtained by ARFI, this will be conducted before and after treatment for hepatitis c and is measured in m/sec
Time Frame
2 years
Title
Hepatic venous pressure gradient before and after treatment of hepatitis c
Description
Hepatic venous pressure gradient would be obtained by catheterization of the hepatic vein, this will be conducted before and after treatment for hepatitis c and is measured in mmHg
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age 18-85 HCV infection (HCV-RNA positive) Compensated cirrhosis will be defined histologically and/or clinically (presence of compatible lab findings (platelet count ≤ 150,000, total bilirubin ≥ 2, serum albumin ≤ 3.5, INR ≥ 1.2) PLUS compatible physical exam features (cutaneous stigmata, gynecomastia in men, or splenomegaly) OR compatible radiological findings (nodular liver surface, splenomegaly, and/or collaterals). (The ultimate confirmation of the diagnosis of cirrhosis will be a baseline HVPG > 5 mmHg) Planned anti-HCV therapy in the next 3 months Exclusion Criteria: Any clinically-evident complication of cirrhosis that defines decompensation : jaundice, ascites, variceal hemorrhage, overt hepatic encephalopathy) Hepatocellular carcinoma Co-infection with HBV or HIV Ongoing alcohol abuse Occlusive portal thrombosis, Presence of comorbid conditions conferring a life expectancy<1 year, history of allergy to iodides, pregnancy
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Guadalupe Garcia-Tsao, MD
Organizational Affiliation
VA Connecticut Healthcare System
Official's Role
Principal Investigator
Facility Information:
Facility Name
Yale-New Haven Hospital
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06511
Country
United States
Facility Name
VA Connecticut Healthcare System
City
West Haven
State/Province
Connecticut
ZIP/Postal Code
06516
Country
United States

12. IPD Sharing Statement

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