Noninvasive Subharmonic Aided Pressure Estimation of Portal Hypertension

NCT ID: NCT02489045

Last Updated: 2021-08-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 178 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-04-06
• Study Completion Date: 2019-03-31

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.

Conditions

Liver Diseases; Portal Hypertension

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

SHAPE measurement

48 µl of Sonazoid microbubbles (GE Healthcare, Oslo, Norway) will be co-infused at a rate of 0.024 µl/kg body weight/minute together with a 0.9% NaCl solution infused at a rate of at least 2 ml/min.

Group Type: EXPERIMENTAL

SHAPE measurement (Sonazoid ultrasoud contrast agent)

Intervention Type: DRUG

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.

Interventions

SHAPE 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.

Intervention Type: DRUG

Other Intervention Names

Sonazoid

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.

• Minimum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Pennsylvania

OTHER

Sponsor Role: collaborator

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

NIH

Sponsor Role: collaborator

Thomas Jefferson University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Flemming Forsberg, PhD

Role: PRINCIPAL_INVESTIGATOR

Thomas Jefferson University

Locations

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Thomas Jefferson University, Dept of Radiology

Philadelphia, Pennsylvania, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 23525208 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33201789 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

R01DK098526

Identifier Type: NIH

Identifier Source: secondary_id

View Link

14F.113

Identifier Type: -

Identifier Source: org_study_id