Impact of Transjugular Intrahepatic Portosystemic Shunts on Liver Stiffness

Pilot study examining changes in liver stiffness measured by ultrasound before and after TIPS creation

Study Overview

• Status: Terminated
• Conditions: Portal Hypertension; Liver Fibroses
• Intervention / Treatment: Diagnostic test: Ultrasound

Detailed Description

Single arm pilot study of adults ≥18yo investigating changes in liver stiffness as measured by ultrasound acoustic radiation force impulse (ARFI) before and after creation of TIPS. Duration of participation is 30 days from TIPS creation. TIPS creation with Viatorr stent graft will be in accordance with its FDA-approved indication for symptomatic portal hypertension and per the manufacturer's instructions for use. Liver stiffness will be measured on pre-TIPS and post-TIPS ultrasounds using Phillips Epiq Ultrasound systems equipped with ElastPQ ultrasound shear wave elastography. Both ultrasounds will be performed at times which are standard of care before and after TIPS creation. Primary objectives include liver stiffness as measured by ultrasound acoustic radiation force impulse (ARFI) before and after creation of TIPS. Secondary objectives include change in portosystemic gradient, clinical success as measured by difference in frequency of repeat paracentesis post-TIPS or freedom from recurrence of variceal bleeding and rate of hepatic encephalopathy. Exploratory objectives include serum biomarkers of liver stiffness.

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Hospital of the University of Pennsylvania

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 79 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Symptomatic portal hypertension secondary to cirrhosis undergoing elective outpatient TIPS
• Age >18, Age <80
• Capable of giving informed consent

Exclusion Criteria:

• Coagulopathy defined as international normalized ration (INR) >2 which cannot be corrected with fresh frozen plasma
• Platelet count <50,000/microliter, which cannot be corrected with platelet transfusion
• BMI >35 and/or cirrhosis due to non-alcoholic steatohepatitis (due to inaccurate elastography measurements in patients with fatty liver)
• Urgent or emergent TIPS for bleeding
• Portal vein thrombosis with in the main, 1st, or 2nd order branches of the portal vein
• Hepatic vein thrombosis (ie no Budd Chiari syndrome)
• Excessive alcohol use defined as more than 2 oz in 24 hours on any individual day within the last 30 days
• Inability to provide informed consent
• Pregnant or nursing women
• Enrollment in concurrent therapeutic trial for symptomatic portal hypertension

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Open Label; All enrolled participants will undergo hepatic ultrasound with acoustic radiation force impulse (ARFI) before and 30 days after creation of TIPS.	Diagnostic test: Ultrasound; Hepatic ultrasound using gray scale, color Doppler, and spectral Doppler imaging to evaluate hepatic vein and portal vein patency, direction and velocity of flow respectively. ARFI will be performed in the right hepatic lobe. Three measurements of stiffness (m/s) will be performed and the mean value recorded.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Decrease in Liver Stiffness	The primary study endpoint will be decrease in liver stiffness following TIPS creation as measured by ARFI using mean propagation velocity values in meters per second. Mean normal values and mean values indicating severe fibrosis range about 0.8-1.7 m/s and about 1-3.4 m/s respectively. We hypothesize TIPS creation will reduce the liver stiffness by > 50%. Change in liver stiffness will be correlated to change in PSG.	Pre-TIPS and 30 days Post-TIPS creation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PSG (mm hg) and ARFI (m/s) Correlation	Baseline PSG (mm Hg) correlation to baseline liver stiffness by ultrasound ARFI (m/s)	Pre-TIPS and 30 days Post-TIPS creation
Frequency of Paracentesis and Recurrence of Variceal Bleeding	Difference in frequency of paracentesis and freedom from recurrence of variceal bleeding at 30 days and 12 months post-TIPS placement	30 days Post-TIPS and 12 months Post-TIPS creation
Hyaluronic Acid and ARFI Correlation	Correlation of hyaluronic acid, a serum marker of liver stiffness, with baseline ARFI measurements, non-invasive radiographic assessment of liver stiffness	Pre-TIPS and 30 days Post-TIPS creation
Tissue Inhibitor of Metalloproteinase-1 and ARFI Correlation	Correlation of tissue inhibitor of metalloproteinase-1, a serum marker of liver stiffness, with baseline ARFI measurements, non-invasive radiographic assessment of liver stiffness	Pre-TIPS and 30 days Post-TIPS creation

Collaborators and Investigators

• Sponsor: University of Pennsylvania
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Kimberly Forde, MD, MHS, University of Pennsylvania

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2016
• Primary Completion (Actual): April 3, 2019
• Study Completion (Actual): April 3, 2019

Study Registration Dates

• First Submitted: October 4, 2017
• First Submitted That Met QC Criteria: November 17, 2017
• First Posted (Actual): November 24, 2017

Study Record Updates

• Last Update Posted (Actual): October 1, 2019
• Last Update Submitted That Met QC Criteria: September 12, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Liver Diseases; Fibrosis; Liver Cirrhosis; Hypertension, Portal
• Other Study ID Numbers: 826196; U54CA193417 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes