Clinical trial NCT02508298: 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
Overall status: COMPLETED
Phase: NA
Conditions: Portal Hypertension
Cirrhosis
Keywords: ICG
ARFI
portal hypertension
cirrhosis
diagnostic study
Lead sponsor: VA Connecticut Healthcare System
Sponsor class: FED
First posted: 2015-07-24
Enrollment: 41
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

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.

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

Primary outcomes:
measure: Indocyanine Green before and after treatment of hepatitis c
timeFrame: 2 years
Secondary outcomes:
measure: Spleen stiffness before and after treatment of hepatitis c
timeFrame: 2 years
measure: Liver stiffness before and after treatment of hepatitis c
timeFrame: 2 years
measure: Hepatic venous pressure gradient before and after treatment of hepatitis c
timeFrame: 2 years
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Yale-New Haven Hospital
state: Connecticut
city: West Haven
country: United States
facility: VA Connecticut Healthcare System
state: Connecticut
Study officials:
affiliation: VA Connecticut Healthcare System
name: Guadalupe Garcia-Tsao, MD
role: PRINCIPAL_INVESTIGATOR
References: