RecruitingPhase 3NCT05470205

Noninvasive Subharmonic Aided Pressure Estimation of Portal Hypertension; Renewal

Noninvasive Subharmonic Aided Pressure Estimation of Portal Hypertension

Sponsor

Thomas Jefferson University

Enrollment

660 participants

Start Date

Nov 28, 2022

Study Type

INTERVENTIONAL

Conditions

Liver Diseases Portal Hypertension

Summary

This is an open-label, non-randomized trial that will be conducted at three clinical sites, Thomas Jefferson University (TJU), the Hospital of the University of Pennsylvania (HUP) and University of Bern (UB). Enrollment will be allocated into one of 4 different cohorts depending on the inclusion criteria for each cohort. Cohort 1: Patients scheduled for hepatic vein pressure gradient (HVPG) measurements will subsequently undergo two consecutive SHAPE (subharmonic aided pressure estimation) procedures using different ultrasound contrast agents (Definity \[Lantheus Medical Imaging, N Bilerica, MA, USA\] and Sonazoid \[GE Healthcare, Oslo, Norway\] in randomized order) to estimate portal pressures with a Logiq E10 scanner (GE Healthcare, Waukesha, WI, USA) and determine the reproducibility of the SHAPE algorithm. Cohort 2: Patients identified as having clinically significant portal hypertension (CSPH) will be monitored by SHAPE with Sonazoid for the duration of this project (18-24 months on average). These subjects will have follow-up ultrasound scans every 6 ± 2 months to check for hepatocellular carcinoma (HCC) (using the Barcelona-Liver Cancer staging system) as well as ascites and at those times a repeat SHAPE examination will be performed. Liver stiffness values will be measured with elastography as well. This cohort will examine if serial SHAPE can accurately predict development of ascites and other liver related events in patients with compensated cirrhosis undergoing routine HCC surveillance in a multi-center setting. Cohort 3: Subjects newly diagnosed with portal hypertension and starting treatment with non-selective β-blockers will be monitored with SHAPE and results compared to elastography measurements of liver stiffness with standard assessments (e.g., serum liver function tests and measurement of spleen size as well as platelet count). This cohort will establish if SHAPE can be used to monitor treatment response in patients identified with portal hypertension. Cohort 4: Patients with compensated advanced chronic liver disease scheduled for an endoscopy examination for screening of varices relative to the Baveno VI and the expanded-Baveno VI criteria as well as the AST to Platelet Ratio Index will undergo a SHAPE examination. This cohort will compare the predictive ability of SHAPE for allocating patients with compensated advanced chronic liver disease to screening of varices compared to the current standard of care.

Eligibility

Min Age: 18 Years

Inclusion Criteria14

All subjects accepted for this trial must fulfill all the following criteria:
Be at least 18 years of age.
Be medically stable.
If a female of child-bearing potential, must have a negative pregnancy test.
Be conscious and able to comply with study procedures.
Have read and signed the IRB-approved Informed Consent form for participating in the study.
Cohort 1:
• Be scheduled for transjugular liver biopsy where HVPG measurements will be obtained
Cohort 2:
• Have clinically significant portal hypertension undergoing routine HCC surveillance
Cohort 3:
• Have a diagnosis of portal hypertension and starting treatment with non-selective β-blockers
Cohort 4:
• Have clinically significant portal hypertension and be scheduled for endoscopy to screen for varices

Exclusion Criteria17

Females who are pregnant or nursing.
Patients with pulmonary hypertension or unstable cardiopulmonary conditions
Patients currently on chemotherapy or with other primary cancers requiring systemic or hepatic loco-regional treatment.
Patients who are medically unstable, patients who are seriously or terminally ill, and patients whose clinical course is unpredictable. For example:
Patients on life support or in a critical care unit.
Patients with unstable occlusive disease (e.g., crescendo angina)
Patients with clinically unstable cardiac arrhythmias, such as recurrent ventricular tachycardia.
Patients with uncontrolled congestive heart failure (NYHA Class IV)
Patients with recent cerebral hemorrhage.
Patients who have undergone surgery within 24 hours prior to the study sonographic examination.
Patients with a history of anaphylactic allergy to eggs or egg products, manifested by one or more of the following symptoms: generalized urticaria, difficulty in breathing, swelling of the mouth and throat, hypotension, or shock. (Subjects with nonanaphylactic allergies to eggs or egg products may be enrolled in the study, but must be watched carefully for 1 hour following the administration of Sonazoid).
Patients with congenital heart defects.
Patients with severe emphysema, pulmonary vasculitis, or a history of pulmonary emboli.
Patients with respiratory distress syndrome
Patients with thrombosis within the hepatic, portal, or mesenteric veins.
Patients with grade 2 and above of hepatic encephalopathy within the last 3 months
• Patients with a history of anaphylactic allergy to perflutren (PEG) or any other components of Definity

Interventions

DRUGSHAPE measurement (Sonazoid ultrasoud contrast agent)

Three vials with 48 µl of Sonazoid (GE Healthcare, Oslo, Norway) microbubbles (6 ml) will be prepared and drawn into a 10 ml syringe, placed in a syringe pump. Sonazoid will be co-infused at a rate of 0.024 µl/kg body weight/minute (suspension infusion rate of 0.18 ml/kg/hour) together with a 0.9% NaCl solution infused at a rate of at least 2 ml/min.

DRUGSHAPE measurement (Definity ultrasoud contrast agent)

Two vials with 3 mL of Definity will be mixed and diluted in 50 mL of normal saline, yielding a concentration of 49.4 μL/mL, and infused at a rate of at least 4 ml/min.