Surrogate Markers of Portal Pressure

NCT ID: NCT02508298

Last Updated: 2019-11-25

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

41 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-04-30

Study Completion Date

2019-07-31

Brief Summary

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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

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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.

Conditions

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Portal Hypertension Cirrhosis

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

DIAGNOSTIC

Blinding Strategy

NONE

Study Groups

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Indocyanine green retention test

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).

Group Type ACTIVE_COMPARATOR

HVPG

Intervention Type PROCEDURE

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.

Indocyanine Green Retention test

Intervention Type DRUG

As decribed in arm descriptions

Liver stiffness measurement

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).

Group Type ACTIVE_COMPARATOR

HVPG

Intervention Type PROCEDURE

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.

Liver stiffness measurement

Intervention Type DEVICE

As decribed in arm descriptions; perfromed by ARFI

Spleen stiffness measurement

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).

Group Type ACTIVE_COMPARATOR

HVPG

Intervention Type PROCEDURE

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.

Spleen stiffness measurement

Intervention Type DEVICE

As decribed in arm descriptions; performed by ARFI

Interventions

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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.

Intervention Type PROCEDURE

Indocyanine Green Retention test

As decribed in arm descriptions

Intervention Type DRUG

Liver stiffness measurement

As decribed in arm descriptions; perfromed by ARFI

Intervention Type DEVICE

Spleen stiffness measurement

As decribed in arm descriptions; performed by ARFI

Intervention Type DEVICE

Other Intervention Names

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Hepatic Venous Portal Gradient ICG test LS SS

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

85 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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VA Connecticut Healthcare System

FED

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Guadalupe Garcia-Tsao, MD

Role: PRINCIPAL_INVESTIGATOR

VA Connecticut Healthcare System

Locations

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Yale-New Haven Hospital

New Haven, Connecticut, United States

Site Status

VA Connecticut Healthcare System

West Haven, Connecticut, United States

Site Status

Countries

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United States

Other Identifiers

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GGT0037

Identifier Type: -

Identifier Source: org_study_id

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