Liver DiseasesPhase 3NCT05470205
Noninvasive Subharmonic Aided Pressure Estimation of Portal Hypertension; Renewal
A Phase 3 study testing SHAPE measurement (Sonazoid ultrasoud contrast agent) and SHAPE measurement (Definity ultrasoud contrast agent) in people with Liver Diseases and Portal Hypertension, run by Thomas Jefferson University at 3 sites in 2 countries.
Trial summary
This is an open-label, non-randomized trial that will be conducted at three clinical sites, Thomas Jefferson University (TJU), the Hospital of the University of Pennsylvania (HUP) and University of Bern (UB). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Liver Diseases, Portal Hypertension
- What is being tested?
- SHAPE measurement (Sonazoid ultrasoud contrast agent) and SHAPE measurement (Definity ultrasoud contrast agent)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 660 participants
- Where
- 3 sitesin 2 countries
- Study dates
- 28 Nov 2022to 30 Apr 2028
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Show all 15Show fewer
- 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
Who cannot join
- 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)
Show all 18Show fewer
- 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
Trial locations and contacts
3 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
3 sites in 2 countries
United States2 sites, 2 recruiting
- Recruiting
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Michael Soulen, MD, 215-615-3591, Michael.Soulen@pennmedicine.upenn.edu
Susan Schultz, BS, RDMS, 215-573-0972, Susan.Schultz@pennmedicine.upenn.edu
- Recruiting
Thomas Jefferson University, Dept of Radiology
Philadelphia, Pennsylvania, 19107
Flemming Forsberg, PhD, 215-955-4870, flemming.forsberg@jefferson.edu
Cynthia Miller, RN, 215-955-8108, Cynthia.L.Miller.3@jefferson.edu
Switzerland1 site, 1 recruiting
- Recruiting
University of Bern
Bern, 3010
Annalisa Berzigotti, MD, PhD, +41 31 632 3391, Annalisa.Berzigotti@insel.ch
Monique Obertin, +41 31 632 3569, monique.obertin@dbmr.unibe.ch
About this study
Official title: Noninvasive Subharmonic Aided Pressure Estimation of Portal Hypertension
This is an open-label, non-randomized trial that will be conducted at three clinical sites, Thomas Jefferson University (TJU), the Hospital of the University of Pennsylvania (HUP) and University of Bern (UB). Enrollment will be allocated into one of 4 different cohorts depending on the inclusion criteria for each cohort.
Cohort 1:
Read more
Patients scheduled for hepatic vein pressure gradient (HVPG) measurements will subsequently undergo two consecutive SHAPE (subharmonic aided pressure estimation) procedures using different ultrasound contrast agents (Definity [Lantheus Medical Imaging, N Bilerica, MA, USA] and Sonazoid [GE Healthcare, Oslo, Norway] in randomized order) to estimate portal pressures with a Logiq E10 scanner (GE Healthcare, Waukesha, WI, USA) and determine the reproducibility of the SHAPE algorithm.
Cohort 2:
Patients identified as having clinically significant portal hypertension (CSPH) will be monitored by SHAPE with Sonazoid for the duration of this project (18-24 months on average). These subjects will have follow-up ultrasound scans every 6 ± 2 months to check for hepatocellular carcinoma (HCC) (using the Barcelona-Liver Cancer staging system) as well as ascites and at those times a repeat SHAPE examination will be performed. Liver stiffness values will be measured with elastography as well. This cohort will examine if serial SHAPE can accurately predict development of ascites and other liver related events in patients with compensated cirrhosis undergoing routine HCC surveillance in a multi-center setting.
Cohort 3:
Subjects newly diagnosed with portal hypertension and starting treatment with non-selective β-blockers will be monitored with SHAPE and results compared to elastography measurements of liver stiffness with standard assessments (e.g., serum liver function tests and measurement of spleen size as well as platelet count). This cohort will establish if SHAPE can be used to monitor treatment response in patients identified with portal hypertension.
Cohort 4:
Patients with compensated advanced chronic liver disease scheduled for an endoscopy examination for screening of varices relative to the Baveno VI and the expanded-Baveno VI criteria as well as the AST to Platelet Ratio Index will undergo a SHAPE examination. This cohort will compare the predictive ability of SHAPE for allocating patients with compensated advanced chronic liver disease to screening of varices compared to the current standard of care.
Read the detailed description
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.
- Conditions
- Liver Diseases, Portal Hypertension
- Being tested
- SHAPE measurement (Sonazoid ultrasoud contrast agent), SHAPE measurement (Definity ultrasoud contrast agent)
- Medical subject headings
- Liver Diseases, Hypertension, Portal
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SHAPE measurement (Sonazoid ultrasoud contrast agent)Drug
Also called Sonazoid
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.
SHAPE measurement (Definity ultrasoud contrast agent)Drug
Also called Definity
Two vials with 3 mL of Definity will be mixed and diluted in 50 mL of normal saline, yielding a concentration of 49.4 μL/mL, and infused at a rate of at least 4 ml/min.
| Study group | Role | What they receive |
|---|---|---|
| Reproducibility - Cohort 1 | Experimental | Patients scheduled for hepatic venous pressure gradient (HVPG) measurements will subsequently undergo two consecutive SHAPE procedures using different ultrasound contrast agents (Definity and Sonazoid in randomized order) to estimate portal pressures with a Logiq E10 scanner (GE Healthcare).
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.
Two vials with 3 mL of Definity will be mixed and diluted in 50 mL of normal saline, yielding a concentration of 49.4 μL/mL, and infused at a rate of at least 4 ml/min. Receives: Drug: SHAPE measurement (Sonazoid ultrasoud contrast agent); Drug: SHAPE measurement (Definity ultrasoud contrast agent) |
| HCC monitoring - Cohort 2 | Experimental | Patients identified as having CSPH will be monitored every 6 ± 2 months to check for HCC by SHAPE with Sonazoid for the duration of this project ( for 18-24 months on average).
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. Receives: Drug: SHAPE measurement (Sonazoid ultrasoud contrast agent) |
| New β-blockers - Cohort 3 | Experimental | Patients newly diagnosed with portal hypertension and starting treatment with non-selective β-blockers will be monitored with SHAPE 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. Receives: Drug: SHAPE measurement (Sonazoid ultrasoud contrast agent) |
| Ccreening for varices - Cohort 4 | Experimental | Patients with compensated advanced chronic liver disease scheduled for an endoscopy examination for screening of varices according to the Baveno VI or the expanded-Baveno VI criteria as well as the AST to Platelet Ratio Index and FIB-4 will undergo a SHAPE examination.
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. Receives: Drug: SHAPE measurement (Sonazoid ultrasoud contrast agent) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Reproducibility of SHAPE liver pressure measurements
Evaluate the use of in vivo SHAPE with 2 ultrasound contrast agents (Sonazoid and Definity) for determining the presence of portal hypertension in patients undergoing a transjugular liver biopsy using catheter based pressure measurements as the reference standard.
Measured: during procedure
Number of subjects who develop ascites during follow-up
Determine if SHAPE estimates of portal vein pressures in patients with compensated cirrhosis can predict the development of ascites (i.e., the progression into decompensated cirrhosis or HVPG > 16 mmHg).
Measured: up to 18 months
Number of subjects who experience clinical decompensation events (including the development of variceal bleeding) during follow-up
Determine if SHAPE measurements can monitor treatment response (i.e., the ability to accurately assess the response to non-selective beta blockers) in patients newly diagnosed with portal hypertension better than elastography.
Measured: up to 18 months
Number of subjects who present with esophageal or gastric varices on endoscopy
In subjects allocated to endoscopic screening for varices based on their clinical risk assessment the outcome of the endoscopic procedure will be compared to their SHAPE values
Measured: baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jul 2022
- Study start28 Nov 2022
- Primary completion28 Feb 2028 (estimated)
- Study completion30 Apr 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Liver DiseasesStudies of the same condition, open and under way.
- More trials run by Thomas Jefferson UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 660 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Thomas Jefferson University
- Sponsor type
- University, hospital or other
- Collaborators
- University of Pennsylvania, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), University of Bern
- Responsible party
- Sponsor
- Investigators
- Flemming Forsberg, PhD, Principal investigator, Thomas Jefferson University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05470205
- Sponsor's protocol ID
- 21F.1224
- Other IDs
- 2R01DK098526
- Status last verified
- Sep 2026
- First submitted
- 13 Jun 2022
- Last updated
- 2 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: This project will generate subharmonic ultrasound data corresponding to portal pressures in the liver from the patients who will be recruited in this study. In addition other conventional measurements will be obtained during the clinical phases of this project. The clinical data will be anonymized to remove any patient information. All of the data collected as in this project will be uploaded on Zenodo.org and made openly available using the Zenodo platform, because it accepts any file format and assigns the uploads a Digital Object Identifier (DOI) to make uploads easily accessible and citable.
Publications
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.
PubMed 23525208Gupta 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.
PubMed 33201789Gupta I, Fenkel JM, Eisenbrey JR, Machado P, Stanczak M, Wessner CE, Shaw CM, Miller C, Soulen MC, Wallace K, Forsberg F. A Noninvasive Ultrasound Based Technique to Identify Treatment Responders in Patients with Portal Hypertension. Acad Radiol. 2021 Nov;28 Suppl 1(Suppl 1):S128-S137. doi: 10.1016/j.acra.2020.11.023. Epub 2020 Dec 17.
PubMed 33341374Machado P, Gupta I, Gummadi S, Stanczak M, Wessner CE, Fenkel JM, Shaw CM, Shamini-Noori S, Schultz S, Soulen MC, Sehgal CM, Wallace K, Eisenbrey JR, Forsberg F. Hepatic Vein Contrast-Enhanced Ultrasound Subharmonic Imaging Signal as a Screening Test for Portal Hypertension. Dig Dis Sci. 2021 Dec;66(12):4354-4360. doi: 10.1007/s10620-020-06790-6. Epub 2021 Jan 4.
PubMed 33392869Forsberg F, Gupta I, Machado P, Shaw CM, Fenkel JM, Wallace K, Eisenbrey JR. Contrast-Enhanced Subharmonic Aided Pressure Estimation (SHAPE) using Ultrasound Imaging with a Focus on Identifying Portal Hypertension. J Vis Exp. 2020 Dec 5;(166):10.3791/62050. doi: 10.3791/62050.
PubMed 33346203Machado P, Gupta I, Fenkel JM, Gummadi S, Stanczak M, Wessner CE, Shaw CM, Schultz S, Soulen MC, Wallace K, Eisenbrey JR, Forsberg F. Ultrasound Pressure Estimation for Diagnosing Portal Hypertension in Patients Undergoing Dialysis for Chronic Kidney Disease. J Ultrasound Med. 2022 Sep;41(9):2181-2189. doi: 10.1002/jum.15897. Epub 2021 Dec 1.
PubMed 34850412
Study at a glance
From the registry record, last updated by the sponsor on 2 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Noninvasive Subharmonic Aided Pressure Estimation of Portal Hypertension
- ClinicalTrials.gov ID
- NCT05470205
- Acronym / sponsor ID
- 21F.1224
- Conditions
- Liver Diseases, Portal Hypertension
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 660 participants (estimated)
- Lead sponsor
- Thomas Jefferson UniversityUniversity, hospital or other
- Collaborators
- University of Pennsylvania, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), University of Bern
- Study start
- 28 Nov 2022 (actual)
- Primary completion
- 28 Feb 2028 (estimated)
- Study completion
- 30 Apr 2028 (estimated)
- First posted
- 22 Jul 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is an open-label, non-randomized trial that will be conducted at three clinical sites, Thomas Jefferson University (TJU), the Hospital of the University of Pennsylvania (HUP) and University of Bern (UB). Enrollment will be allocated into one of 4 different cohorts depending on the inclusion criteria for each cohort.
Cohort 1:
Patients scheduled for hepatic vein pressure gradient (HVPG) measurements will subsequently undergo two consecutive SHAPE (subharmonic aided pressure estimation) procedures using different ultrasound contrast agents (Definity [Lantheus Medical Imaging, N Bilerica, MA, USA] and Sonazoid [GE Healthcare, Oslo, Norway] in randomized order) to estimate portal pressures with a Logiq E10 scanner (GE Healthcare, Waukesha, WI, USA) and determine the reproducibility of the SHAPE algorithm.
Cohort 2:
Patients identified as having clinically significant portal hypertension (CSPH) will be monitored by SHAPE with Sonazoid for the duration of this project (18-24 months on average). These subjects will have follow-up ultrasound scans every 6 ± 2 months to check for hepatocellular carcinoma (HCC) (using the Barcelona-Liver Cancer staging system) as well as ascites and at those times a repeat SHAPE examination will be performed. Liver stiffness values will be measured with elastography as well. This cohort will examine if serial SHAPE can accurately predict development of ascites and other liver related events in patients with compensated cirrhosis undergoing routine HCC surveillance in a multi-center setting.
Cohort 3:
Subjects newly diagnosed with portal hypertension and starting treatment with non-selective β-blockers will be monitored with SHAPE and results compared to elastography measurements of liver stiffness with standard assessments (e.g., serum liver function tests and measurement of spleen size as well as platelet count). This cohort will establish if SHAPE can be used to monitor treatment response in patients identified with portal hypertension.
Cohort 4:
Patients with compensated advanced chronic liver disease scheduled for an endoscopy examination for screening of varices relative to the Baveno VI and the expanded-Baveno VI criteria as well as the AST to Platelet Ratio Index will undergo a SHAPE examination. This cohort will compare the predictive ability of SHAPE for allocating patients with compensated advanced chronic liver disease to screening of varices compared to the current standard of care.
Detailed description
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.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Reproducibility - Cohort 1 | Experimental | Drug: SHAPE measurement (Sonazoid ultrasoud contrast agent), Drug: SHAPE measurement (Definity ultrasoud contrast agent)Patients scheduled for hepatic venous pressure gradient (HVPG) measurements will subsequently undergo two consecutive SHAPE procedures using different ultrasound contrast agents (Definity and Sonazoid in randomized order) to estimate portal pressures with a Logiq E10 scanner (GE Healthcare). 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. Two vials with 3 mL of Definity will be mixed and diluted in 50 mL of normal saline, yielding a concentration of 49.4 μL/mL, and infused at a rate of at least 4 ml/min. |
| HCC monitoring - Cohort 2 | Experimental | Drug: SHAPE measurement (Sonazoid ultrasoud contrast agent)Patients identified as having CSPH will be monitored every 6 ± 2 months to check for HCC by SHAPE with Sonazoid for the duration of this project ( for 18-24 months on average). 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. |
| New β-blockers - Cohort 3 | Experimental | Drug: SHAPE measurement (Sonazoid ultrasoud contrast agent)Patients newly diagnosed with portal hypertension and starting treatment with non-selective β-blockers will be monitored with SHAPE 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. |
| Ccreening for varices - Cohort 4 | Experimental | Drug: SHAPE measurement (Sonazoid ultrasoud contrast agent)Patients with compensated advanced chronic liver disease scheduled for an endoscopy examination for screening of varices according to the Baveno VI or the expanded-Baveno VI criteria as well as the AST to Platelet Ratio Index and FIB-4 will undergo a SHAPE examination. 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- 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.
Key exclusion criteria (18 listed)
- 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 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SHAPE measurement (Sonazoid ultrasoud contrast agent)Also: SonazoidThree 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. | Drug | Ccreening for varices - Cohort 4, HCC monitoring - Cohort 2, New β-blockers - Cohort 3, Reproducibility - Cohort 1 |
| SHAPE measurement (Definity ultrasoud contrast agent)Also: DefinityTwo vials with 3 mL of Definity will be mixed and diluted in 50 mL of normal saline, yielding a concentration of 49.4 μL/mL, and infused at a rate of at least 4 ml/min. | Drug | Reproducibility - Cohort 1 |
Primary outcome
Reproducibility of SHAPE liver pressure measurements
Time frame: during procedure
Evaluate the use of in vivo SHAPE with 2 ultrasound contrast agents (Sonazoid and Definity) for determining the presence of portal hypertension in patients undergoing a transjugular liver biopsy using catheter based pressure measurements as the reference standard.
Number of subjects who develop ascites during follow-up
Time frame: up to 18 months
Determine if SHAPE estimates of portal vein pressures in patients with compensated cirrhosis can predict the development of ascites (i.e., the progression into decompensated cirrhosis or HVPG > 16 mmHg).
Number of subjects who experience clinical decompensation events (including the development of variceal bleeding) during follow-up
Time frame: up to 18 months
Determine if SHAPE measurements can monitor treatment response (i.e., the ability to accurately assess the response to non-selective beta blockers) in patients newly diagnosed with portal hypertension better than elastography.
Number of subjects who present with esophageal or gastric varices on endoscopy
Time frame: baseline
In subjects allocated to endoscopic screening for varices based on their clinical risk assessment the outcome of the endoscopic procedure will be compared to their SHAPE values
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Oct 2026.
- Background: PubMed 23525208Eisenbrey 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.
- Background: PubMed 33201789Gupta 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.
- Background: PubMed 33341374Gupta I, Fenkel JM, Eisenbrey JR, Machado P, Stanczak M, Wessner CE, Shaw CM, Miller C, Soulen MC, Wallace K, Forsberg F. A Noninvasive Ultrasound Based Technique to Identify Treatment Responders in Patients with Portal Hypertension. Acad Radiol. 2021 Nov;28 Suppl 1(Suppl 1):S128-S137. doi: 10.1016/j.acra.2020.11.023. Epub 2020 Dec 17.
- Background: PubMed 33392869Machado P, Gupta I, Gummadi S, Stanczak M, Wessner CE, Fenkel JM, Shaw CM, Shamini-Noori S, Schultz S, Soulen MC, Sehgal CM, Wallace K, Eisenbrey JR, Forsberg F. Hepatic Vein Contrast-Enhanced Ultrasound Subharmonic Imaging Signal as a Screening Test for Portal Hypertension. Dig Dis Sci. 2021 Dec;66(12):4354-4360. doi: 10.1007/s10620-020-06790-6. Epub 2021 Jan 4.
- Background: PubMed 33346203Forsberg F, Gupta I, Machado P, Shaw CM, Fenkel JM, Wallace K, Eisenbrey JR. Contrast-Enhanced Subharmonic Aided Pressure Estimation (SHAPE) using Ultrasound Imaging with a Focus on Identifying Portal Hypertension. J Vis Exp. 2020 Dec 5;(166):10.3791/62050. doi: 10.3791/62050.
- Background: PubMed 34850412Machado P, Gupta I, Fenkel JM, Gummadi S, Stanczak M, Wessner CE, Shaw CM, Schultz S, Soulen MC, Wallace K, Eisenbrey JR, Forsberg F. Ultrasound Pressure Estimation for Diagnosing Portal Hypertension in Patients Undergoing Dialysis for Chronic Kidney Disease. J Ultrasound Med. 2022 Sep;41(9):2181-2189. doi: 10.1002/jum.15897. Epub 2021 Dec 1.
- Individual participant dataSharing planned: Yes. This project will generate subharmonic ultrasound data corresponding to portal pressures in the liver from the patients who will be recruited in this study. In addition other conventional measurements will be obtained during the clinical phases of this project. The clinical data will be anonymized to remove any patient information. All of the data collected as in this project will be uploaded on Zenodo.org and made openly available using the Zenodo platform, because it accepts any file format and assigns the uploads a Digital Object Identifier (DOI) to make uploads easily accessible and citable.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Flemming Forsberg, PhD principal investigator
Thomas Jefferson University
3 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing SHAPE measurement (Sonazoid ultrasoud contrast agent) and SHAPE measurement (Definity ultrasoud contrast agent) in people with Liver Diseases and Portal Hypertension, run by Thomas Jefferson University at 3 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 2 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States, Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Flemming Forsberg, PhD (215-955-4870, flemming.forsberg@jefferson.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Reproducibility of SHAPE liver pressure measurements (time frame: during procedure). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05470205, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Oct 2026.