Liver Fibroses, Portal Hypertension
Conditions
Brief summary
Pilot study examining changes in liver stiffness measured by ultrasound before and after TIPS creation
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.
Interventions
DIAGNOSTIC_TESTUltrasound
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.
Sponsors
National Cancer Institute (NCI)
University of Pennsylvania
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 79 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Decrease in Liver Stiffness | Pre-TIPS and 30 days Post-TIPS creation | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PSG (mm hg) and ARFI (m/s) Correlation | Pre-TIPS and 30 days Post-TIPS creation | Baseline PSG (mm Hg) correlation to baseline liver stiffness by ultrasound ARFI (m/s) |
| Frequency of Paracentesis and Recurrence of Variceal Bleeding | 30 days Post-TIPS and 12 months Post-TIPS creation | Difference in frequency of paracentesis and freedom from recurrence of variceal bleeding at 30 days and 12 months post-TIPS placement |
| Hyaluronic Acid and ARFI Correlation | Pre-TIPS and 30 days Post-TIPS creation | Correlation of hyaluronic acid, a serum marker of liver stiffness, with baseline ARFI measurements, non-invasive radiographic assessment of liver stiffness |
| Tissue Inhibitor of Metalloproteinase-1 and ARFI Correlation | Pre-TIPS and 30 days Post-TIPS creation | Correlation of tissue inhibitor of metalloproteinase-1, a serum marker of liver stiffness, with baseline ARFI measurements, non-invasive radiographic assessment of liver stiffness |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Open Label All enrolled participants will undergo hepatic ultrasound with acoustic radiation force impulse (ARFI) before and 30 days after creation of TIPS.
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. | 1 |
| Total | 1 |
Baseline characteristics
| Characteristic | Open Label |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants |
| Age, Continuous | 51 Years |
| Childs-Pugh Score | 8 units on a scale |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 1 Participants |
| Region of Enrollment United States | 1 Participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 1 |
| other Total, other adverse events | 0 / 1 |
| serious Total, serious adverse events | 0 / 1 |
Outcome results
Primary
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.
Time frame: Pre-TIPS and 30 days Post-TIPS creation
Population: This study was terminated early due to low enrollment. Only 1 subject was ever enrolled and as such no data analysis was conducted.
Secondary
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
Time frame: 30 days Post-TIPS and 12 months Post-TIPS creation
Population: This study was terminated early due to low enrollment. Only 1 subject was ever enrolled and as such no data analysis was conducted.
Secondary
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
Time frame: Pre-TIPS and 30 days Post-TIPS creation
Population: This study was terminated early due to low enrollment. Only 1 subject was ever enrolled and as such no data analysis was conducted.
Secondary
PSG (mm hg) and ARFI (m/s) Correlation
Baseline PSG (mm Hg) correlation to baseline liver stiffness by ultrasound ARFI (m/s)
Time frame: Pre-TIPS and 30 days Post-TIPS creation
Population: This study was terminated early due to low enrollment. Only 1 subject was ever enrolled and as such no data analysis was conducted.
Secondary
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
Time frame: Pre-TIPS and 30 days Post-TIPS creation
Population: This study was terminated early due to low enrollment. Only 1 subject was ever enrolled and as such no data analysis was conducted.