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Noninvasive Subharmonic Aided Pressure Estimation of Portal Hypertension

Primary Purpose

Liver Diseases, Portal Hypertension

Status

Completed

Phase

Phase 4

Locations

United States

Study Type

Interventional

Intervention

SHAPE measurement (Sonazoid ultrasoud contrast agent)

About this trial

This is an interventional diagnostic trial for Liver Diseases

Eligibility Criteria

21 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

University of Pennsylvania
Thomas Jefferson University, Dept of Radiology

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

SHAPE measurement

Arm Description

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.

Outcomes

Primary Outcome Measures

Diagnostic Accuracy of SHAPE Liver Pressure Estimates (in dB) for Diagnosing Portal Hypertension With Catheter Pressure Measurements (in mmHg) as the Reference Standard

Evaluate the use of in vivo subharmonic aided pressure estimation (SHAPE as the difference between the optimized subharmonic signal in a hepatic vein and in the portal vein) as a first quantitative screening modality for determining the presence of clinically significant portal hypertension in patients undergoing a transjugular liver biopsy compared to catheter based hepatic-venous pressure gradient measurements (HVPG in mmHg as the reference standard).

SHAPE Liver Pressure Estimates (in dB) Correlation With Catheter Pressure Measurements (in mmHg)

Evaluate the correlation between in vivo subharmonic aided pressure estimation (SHAPE as the difference between the optimized subharmonic signal in a hepatic vein and catheter based hepatic-venous pressure gradient measurements (HVPG in mmHg) in patients undergoing a transjugular liver biopsy.

Comparing SHAPE Results With Blood Work and Concomitant Imaging in Portal Hypertension Patients

Determine if SHAPE measurements (in dB) can provide a quantitative, noninvasive measurement of hepatic venous pressure gradient (HVPG) to monitor disease progression or treatment response in patients identified with portal hypertension by comparing the results to repeat biopsies and/or clinical outcomes.

Secondary Outcome Measures

Full Information

NCT ID

NCT02489045

First Posted

May 14, 2015

Last Updated

July 20, 2021

Sponsor

Thomas Jefferson University

Collaborators

University of Pennsylvania, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

1. Study Identification

Unique Protocol Identification Number

NCT02489045

Brief Title

Noninvasive Subharmonic Aided Pressure Estimation of Portal Hypertension

Official Title

Noninvasive Subharmonic Aided Pressure Estimation of Portal Hypertension

Study Type

Interventional

2. Study Status

Record Verification Date

July 2021

Overall Recruitment Status

Completed

Study Start Date

April 6, 2015 (Actual)

Primary Completion Date

March 31, 2019 (Actual)

Study Completion Date

March 31, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Thomas Jefferson University

Collaborators

University of Pennsylvania, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Liver Diseases, Portal Hypertension

7. Study Design

Primary Purpose

Diagnostic

Study Phase

Phase 4

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

178 (Actual)

8. Arms, Groups, and Interventions

Arm Title

SHAPE measurement

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

SHAPE measurement (Sonazoid ultrasoud contrast agent)

Other Intervention Name(s)

Sonazoid

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.

Primary Outcome Measure Information:

Title

Diagnostic Accuracy of SHAPE Liver Pressure Estimates (in dB) for Diagnosing Portal Hypertension With Catheter Pressure Measurements (in mmHg) as the Reference Standard

Description

Time Frame

up to 1 day

Title

SHAPE Liver Pressure Estimates (in dB) Correlation With Catheter Pressure Measurements (in mmHg)

Description

Time Frame

up to 1 day

Title

Comparing SHAPE Results With Blood Work and Concomitant Imaging in Portal Hypertension Patients

Description

Time Frame

up to 2 hours

10. Eligibility

Sex

All

Minimum Age & Unit of Time

21 Years

Accepts Healthy Volunteers

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Flemming Forsberg, PhD

Organizational Affiliation

Thomas Jefferson University

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Pennsylvania

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19104

Country

United States

Facility Name

Thomas Jefferson University, Dept of Radiology

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19107

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

23525208

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.

Results Reference

background

PubMed Identifier

33201789

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.

Results Reference

derived

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Noninvasive Subharmonic Aided Pressure Estimation of Portal Hypertension

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