Noninvasive Subharmonic Aided Pressure Estimation of Portal Hypertension
Condition: Liver Diseases; Portal Hypertension
MeSH terms: Liver Diseases; Hypertension, Portal; Hypertension
Intervention: SHAPE measurement (Sonazoid ultrasoud contrast agent)
Intervention description: 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.
Phase: Phase 4
Study type: Interventional
Primary purpose: Diagnostic
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 178.0
Sex: All
Minimum age: 21 Years
Healthy volunteers: No

Summary:

      This is an open-label, non-randomized trial that will be conducted at two clinical sites,
      Thomas Jefferson University (TJU) and the Hospital of the University of Pennsylvania (HUP).
      Enrolled patients undergoing trans-jugular liver biopsy with hepatic vein pressure gradient
      (HVPG) measurements will receive a continuous infusion of Sonazoid® (GE Healthcare, Oslo,
      Norway) co-infused with 0.9% NaCl solution over a 5-10 minute time period. Ultrasound imaging
      will be performed using a Logiq 9 scanner with a 4C transducer (GE Healthcare, Milwaukee, WI)
      and the novel SHAPE (subharmonic aided pressure estimation) algorithm will be used to measure
      pressure values in the hepatic and portal veins. Data will be stored on a PC and compared to
      pressure-catheter measurements, Subjects identified in the initial examination as having
      portal hypertension (by HVPG results) will be monitored by SHAPE for up to 18 months. These
      subjects typically have surveillance Computed tomography (CT) or magnetic resonance imaging
      (MRI) scans every 6 months to screen for liver cancer, and at those times a repeat SHAPE
      examination will be performed (ideally within 1 month of their clinically indicated imaging
      follow up appointment). In patients who undergo more frequent screening (generally 3 month
      intervals), SHAPE exams will be performed at 6 month intervals. Any repeat trans-jugular
      liver biopsies performed in this population will also trigger a repeat SHAPE study. Results
      of blood test evaluations (performed every 3 months in this population), medication,
      concomitant imaging study or procedure (including endoscopies) will be noted (all blood tests
      and imaging are clinically indicated only and are not required by this protocol). The end
      point for this part of the study will be any one new complication (e.g., liver cancer) or a
      marked worsening in any complication, liver transplantation, death, or the end of this
      clinical trial (after 3 years). The investigators expect these patients will be monitored
      three times during the course of this clinical trial. The time to reach the end point will be
      noted if a new complication or a marked worsening in any complication occurs.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Be scheduled for trans-jugular liver biopsy the day of the ultrasound procedure.

          -  Be at least 21 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.

        Exclusion Criteria:

          -  Females who are pregnant or nursing.

          -  Patients not scheduled for trans-jugular liver biopsy

          -  Patients who have received an investigational drug in the 30 days before study drug
             administration, or will receive one within 72 h afterwards,.

          -  Patients with known or suspected right-to-left, bi-directional, or transient
             right-to-left cardiac shunts

          -  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 h 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.