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Noninvasive Subharmonic Aided Pressure Estimation of Portal Hypertension; Renewal

NCT05470205 · Thomas Jefferson University
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Official title
Noninvasive Subharmonic Aided Pressure Estimation of Portal Hypertension
About this study
For each SHAPE study (Cohorts 1, 2, 3 and 4), a dose of three vials with 60 μL of Sonazoid microbubbles (6 mL) will be prepared. An infusion of Sonazoid (1.44 μL microbubbles/kg/hour) and saline (120 mL/hour) through an IV line in the antecubital vein (or, if need be, in another suitable vein) will be started. The duration of contrast agent infusion will range from 6 to 10 minutes. For the direct contrast agent comparison in Cohort 1, two vials of Definity will be mixed and diluted in 50 mL of normal saline, yielding a concentration of 49.4 μL/mL, and infused over approximately 10-12 minutes. A waiting period of at least 30 minutes will be observed in Cohort 1 between infusing contrast agents and the order of the contrast agents will be randomized. Once the infusion of contrast has started, ultrasound imaging will be performed with the C1-6-D curvi-linear array (GE Healthcare) to guide SHAPE ROI placement into the portal vein (while also visualizing a hepatic vein). The SHAPE optimization algorithm will be activated and the acoustic power will be adjusted to produce the maximum change in subharmonic amplitudes (i.e., maximizing the sensitivity of SHAPE). Subharmonic raw DICOM data from the microbubbles (i.e., SHAPE) will be acquired at the optimal acoustic power setting in 5 s segments during the infusion of the Sonazoid (or Definity) suspension. All measurements will be repeated three times to allow for averaging of the resulting SHAPE pressure estimates. The SHAPE pressure estimates will be calculated on the Logiq E10 and recorded. Finally, all digital clips will be transferred off-line for backup and to permit repeat calculations of the portal pressure estimates in case new processing parameters are developed as part of this study.
Eligibility criteria
Inclusion Criteria: 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 Exclusion Criteria: * 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 Also there is one additional exclusion criteria for cohort 1: • Patients with a history of anaphylactic allergy to perflutren (PEG) or any other components of Definity
Study design
Enrollment target: 660 participants
Allocation: non_randomized
Masking: none
Age groups: adult, older_adult
Timeline
Starts: 2022-11-28
Estimated completion: 2026-04-30
Last updated: 2025-02-11
Interventions
Drug: SHAPE measurement (Sonazoid ultrasoud contrast agent)Drug: SHAPE measurement (Definity ultrasoud contrast agent)
Primary outcomes
  • Reproducibility of SHAPE liver pressure measurements (during procedure)
  • Number of subjects who develop ascites during follow-up (up to 18 months)
  • Number of subjects who experience clinical decompensation events (including the development of variceal bleeding) during follow-up (up to 18 months)
Sponsor
Thomas Jefferson University · other
With: University of Pennsylvania, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), University of Bern
Contacts & investigators
ContactFlemming Forsberg, PhD · contact · flemming.forsberg@jefferson.edu · 215-955-4870
ContactCynthia Miller, RN · contact · Cynthia.L.Miller.3@jefferson.edu · 215-955-8108
InvestigatorFlemming Forsberg, PhD · principal_investigator, Thomas Jefferson University
All locations (3)
University of PennsylvaniaRecruiting
Philadelphia, Pennsylvania, United States
Thomas Jefferson University, Dept of RadiologyRecruiting
Philadelphia, Pennsylvania, United States
University of BernRecruiting
Bern, Switzerland
Noninvasive Subharmonic Aided Pressure Estimation of Portal Hypertension; Renewal · TrialPath