Clinical trial NCT02489045: Noninvasive Subharmonic Aided Pressure Estimation of Portal Hypertension
Official title: Noninvasive Subharmonic Aided Pressure Estimation of Portal Hypertension
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Liver Diseases
Portal Hypertension
Lead sponsor: Thomas Jefferson University
Sponsor class: OTHER
Collaborators: name: University of Pennsylvania
name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2015-07-02
Enrollment: 178
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief 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.

Primary outcomes:
measure: Diagnostic Accuracy of SHAPE Liver Pressure Estimates (in dB) for Diagnosing Portal Hypertension With Catheter Pressure Measurements (in mmHg) as the Reference Standard
timeFrame: up to 1 day
measure: SHAPE Liver Pressure Estimates (in dB) Correlation With Catheter Pressure Measurements (in mmHg)
timeFrame: up to 1 day
measure: Comparing SHAPE Results With Blood Work and Concomitant Imaging in Portal Hypertension Patients
timeFrame: up to 2 hours
Secondary outcomes:
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University, Dept of Radiology
state: Pennsylvania
Study officials:
affiliation: Thomas Jefferson University
name: Flemming Forsberg, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Eisenbrey JR, Dave JK, Halldorsdottir VG, Merton DA, Miller C, Gonzalez JM, Machado P, Park S, Dianis S, Chalek CL, Kim CE, Baliff JP, Thomenius KE, Brown DB, Navarro V, Forsberg F. Chronic liver disease: noninvasive subharmonic aided pressure estimation of hepatic venous pressure gradient. Radiology. 2013 Aug;268(2):581-8. doi: 10.1148/radiol.13121769. Epub 2013 Mar 22.
citation: Gupta I, Eisenbrey JR, Machado P, Stanczak M, Wessner CE, Shaw CM, Gummadi S, Fenkel JM, Tan A, Miller C, Parent J, Schultz S, Soulen MC, Sehgal CM, Wallace K, Forsberg F. Diagnosing Portal Hypertension with Noninvasive Subharmonic Pressure Estimates from a US Contrast Agent. Radiology. 2021 Jan;298(1):104-111. doi: 10.1148/radiol.2020202677. Epub 2020 Nov 17.