Surrogate Markers of Portal Pressure

Cirrhosis Clinical Trial

Official title:

Surrogate Markers of Portal Pressure and Changes in Portal Pressure in Patients With Compensated Cirrhosis Undergoing Anti-viral Therapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02508298
• Other study ID #: GGT0037
• Status: Completed
• Phase: N/A
• Start date: April 2014
• Est. completion date: July 2019

Study information

• Verified date: November 2019
• Source: VA Connecticut Healthcare System
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 41
• Est. completion date: July 2019
• Est. primary completion date: July 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• Cirrhosis
• Fibrosis
• Hypertension
• Hypertension, Portal
• Liver Cirrhosis
• Portal Hypertension

Intervention

Procedure:
• HVPG
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.

Drug:
• Indocyanine Green Retention test
As decribed in arm descriptions

Device:
• Liver stiffness measurement
As decribed in arm descriptions; perfromed by ARFI
• Spleen stiffness measurement
As decribed in arm descriptions; performed by ARFI

Locations

Country	Name	City	State
United States	Yale-New Haven Hospital	New Haven	Connecticut
United States	VA Connecticut Healthcare System	West Haven	Connecticut

Sponsors (1)

Lead Sponsor	Collaborator
VA Connecticut Healthcare System

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	2 years
Secondary	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	2 years
Secondary	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	2 years
Secondary	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	2 years