Surrogate Markers of Portal Pressure

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

Sponsoren

Hauptsponsor: VA Connecticut Healthcare System

Quelle VA Connecticut Healthcare System
Kurze Zusammenfassung

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.

detaillierte Beschreibung

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.

Gesamtstatus Completed
Anfangsdatum April 2014
Fertigstellungstermin July 2019
Primäres Abschlussdatum July 2018
Phase N/A
Studientyp Interventional
Primärer Ausgang
Messen Zeitfenster
Indocyanine Green before and after treatment of hepatitis c 2 years
Sekundäres Ergebnis
Messen Zeitfenster
Spleen stiffness before and after treatment of hepatitis c 2 years
Liver stiffness before and after treatment of hepatitis c 2 years
Hepatic venous pressure gradient before and after treatment of hepatitis c 2 years
Einschreibung 41
Bedingung
Intervention

Interventionsart: Procedure

Interventionsname: HVPG

Beschreibung: 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.

Anderer Name: Hepatic Venous Portal Gradient

Interventionsart: Drug

Interventionsname: Indocyanine Green Retention test

Beschreibung: As decribed in arm descriptions

Armgruppenetikett: Indocyanine green retention test

Anderer Name: ICG test

Interventionsart: Device

Interventionsname: Liver stiffness measurement

Beschreibung: As decribed in arm descriptions; perfromed by ARFI

Armgruppenetikett: Liver stiffness measurement

Anderer Name: LS

Interventionsart: Device

Interventionsname: Spleen stiffness measurement

Beschreibung: As decribed in arm descriptions; performed by ARFI

Armgruppenetikett: Spleen stiffness measurement

Anderer Name: SS

Teilnahmeberechtigung

Kriterien:

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

Geschlecht: All

Mindestalter: 18 Years

Maximales Alter: 85 Years

Gesunde Freiwillige: No

Insgesamt offiziell
Nachname Rolle Zugehörigkeit
Guadalupe Garcia-Tsao, MD Principal Investigator VA Connecticut Healthcare System
Ort
Einrichtung:
Yale-New Haven Hospital | New Haven, Connecticut, 06511, United States
VA Connecticut Healthcare System | West Haven, Connecticut, 06516, United States
Standort Länder

United States

Überprüfungsdatum

November 2019

Verantwortliche Partei

Art: Sponsor

Schlüsselwörter
Hat den Zugriff erweitert No
Bedingung Durchsuchen
Anzahl der Waffen 3
Armgruppe

Etikette: Indocyanine green retention test

Art: Active Comparator

Beschreibung: 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).

Etikette: Liver stiffness measurement

Art: Active Comparator

Beschreibung: 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).

Etikette: Spleen stiffness measurement

Art: Active Comparator

Beschreibung: 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).

Studiendesign Info

Zuweisung: Non-Randomized

Interventionsmodell: Single Group Assignment

Hauptzweck: Diagnostic

Maskierung: None (Open Label)

Quelle: ClinicalTrials.gov