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| ID | Type | Description | Link |
|---|---|---|---|
| R01DK098526 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| University of Pennsylvania | OTHER |
| National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) | NIH |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| SHAPE measurement | Experimental | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| SHAPE measurement (Sonazoid ultrasoud contrast agent) | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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). | up to 1 day |
| 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. | up to 1 day |
| 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. | up to 2 hours |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Flemming Forsberg, PhD | Thomas Jefferson University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Pennsylvania | Philadelphia | Pennsylvania | 19104 | United States | ||
| Thomas Jefferson University, Dept of Radiology |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23525208 | Background | 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. | |
| 33201789 | Derived | 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. |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| Follow-up |
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. 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. |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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). | Posted | Number | diagnostic accuracy in percent | up to 1 day |
|
2 hours after infusion of the ultrasound contrast agent
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. 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. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Flemming Forsberg, PhD | Thomas Jefferson University | 215-955-4870 | flemming.forsberg@jefferson.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jul 21, 2014 | Apr 19, 2021 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D008107 | Liver Diseases |
| D006975 | Hypertension, Portal |
| ID | Term |
|---|---|
| D004066 | Digestive System Diseases |
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| ID | Term |
|---|---|
| C069727 | Sonazoid |
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|
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| Philadelphia |
| Pennsylvania |
| 19107 |
| United States |
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| years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Primary | 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. | Posted | Number | correlation coefficient | up to 1 day |
|
|
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| Primary | 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. | Only subjects with clinically significant portal hypertension were included in the follow-up study | Posted | Mean | Standard Deviation | dB | up to 2 hours |
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| 0 |
| 125 |
| 0 |
| 125 |
| 0 |
| 125 |
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