Noninvasive Subharmonic Aided Pressure Estimation of Portal Hypertension

Status: Recruiting
Location: See all (3) locations...
Intervention Type: Drug
Study Type: Interventional
Study Phase: Phase 3
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
Participation Requirements
Sex: All
Minimum Age: 18
Healthy Volunteers: f
View:

⁃ 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.

⁃ Also there are specific inclusion criteria for each cohort:

⁃ 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

Locations
United States
Pennsylvania
Thomas Jefferson University, Dept of Radiology
RECRUITING
Philadelphia
University of Pennsylvania
RECRUITING
Philadelphia
Other Locations
Switzerland
University of Bern
RECRUITING
Bern
Contact Information
Primary
Flemming Forsberg, PhD
flemming.forsberg@jefferson.edu
215-955-4870
Backup
Cynthia Miller, RN
Cynthia.L.Miller.3@jefferson.edu
215-955-8108
Time Frame
Start Date: 2022-11-28
Estimated Completion Date: 2026-04-30
Participants
Target number of participants: 660
Treatments
Experimental: Reproducibility - Cohort 1
Patients scheduled for hepatic venous pressure gradient (HVPG) measurements will subsequently undergo two consecutive SHAPE procedures using different ultrasound contrast agents (Definity and Sonazoid in randomized order) to estimate portal pressures with a Logiq E10 scanner (GE Healthcare).~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.~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.
Experimental: HCC monitoring - Cohort 2
Patients identified as having CSPH will be monitored every 6 ± 2 months to check for HCC by SHAPE with Sonazoid for the duration of this project ( for 18-24 months on average).~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.
Experimental: New β-blockers - Cohort 3
Patients newly diagnosed with portal hypertension and starting treatment with non-selective β-blockers will be monitored with SHAPE 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.
Experimental: Ccreening for varices - Cohort 4
Patients with compensated advanced chronic liver disease scheduled for an endoscopy examination for screening of varices according to the Baveno VI or the expanded-Baveno VI criteria as well as the AST to Platelet Ratio Index and FIB-4 will undergo a SHAPE examination.~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.
Sponsors
Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), University of Bern, University of Pennsylvania
Leads: Thomas Jefferson University

This content was sourced from clinicaltrials.gov