Recruiting
Phase 2

SHAPE

Sponsor:

Thomas Jefferson University

Code:

NCT04720456

Conditions

Hypertension, Portal

Eligibility Criteria

Sex: All

Age: 6 - 21

Healthy Volunteers: Not accepted

Interventions

SHAPE measurement using the ultrasound contrast agent Sonazoid (perfluorobutane microbubbles)

SHAPE measurement using the ultrasound contrast agent Lumason (sulfur hexafluoride lipid-type A microspheres)

Study Details

Brief summary:

Early diagnosis of portal hypertension is difficult as symptoms rarely manifest until the later stages of liver disease. Both cirrhotic and non-cirrhotic portal hypertension can result in life-threatening complications, the most frequent of which is bleeding from esophageal varices. In children, variceal bleeds are associated with mortality rates of 1-3 %, while life-threatening complications have been reported in up to 20 % of children with cirrhosis. Despite the high incidence of portal hypertension in children with liver disease, a noninvasive modality to monitor disease progression and risk of complications is currently lacking. Hence, this trial will investigate the safety and efficacy of subharmonic aided pressure estimation (SHAPE) as a noninvasive ultrasound technique for diagnosing portal hypertension in children.

Conditions

Hypertension, Portal

Study ID

NCT04720456

Start date

Nov 3, 2021

Status verified date

Jan, 2025

Completion date

Aug, 2025

Anticipated

Primary completion date

Jul, 2025

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 6 - 21

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • Patients with a diagnosis of chronic liver disease without portal hypertension.
  • Patients with a diagnosis of chronic liver disease with portal hypertension.

Exclusion Criteria:

  • Subjects who are pregnant.
  • Patients with known or suspected hypersensitivity to egg phosphatidyl serine or with a history of anaphylactic allergy to eggs or egg products.
  • Subjects with allergy to egg products or other components of the ultrasound contrast agents will be excluded.
  • History of allergic reaction to Lumason®, sulfur hexafluoride, sulfur hexafluoride lipid microsphere components, or other ingredients in Lumason (polyethylene glycol, distearoylphosphatidylcholine (DSPC), dipalmitoylphosphatidylglycerol sodium (DPPG-Na), palmitic acid)
  • History of allergic reaction to Sonazoid
  • Patients with biliary atresia with asplenia or polysplenia.
  • Patients with prior liver transplant.
  • Patients with cystic fibrosis.
  • Patients with chronic lung disease.
  • Patients with portal vein thrombosis, cavernous transformation of the portal vein or absent portal vein.
  • Adults not competent/impaired.
  • Patients with significant heart disease or severe congenital heart disease

Study Design

Enrollment

120 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Diagnostic

Interventions and Outcome Measures

Arms

experimental: SHAPE with Sonazoid

Up to 60 children (6-21 years of age) with a diagnosis of chronic liver disease, including some who will have portal hypertension who are followed at The Children's Hospital of Philadelphia (CHOP) will be enrolled in this arm. A SHAPE measurement using the ultrasound contrast agent Sonazoid® (perfluorobutane microbubbles) will be performed during a single visit. A dose of three vials with 16 μL each of microbubbles will be prepared. An infusion of the ultrasound contrast agent at the rate of 0.18 mL/kg/hour will be co-infused with an infusion of saline at the rate of 120 mL/hour resulting in an effective dosage of 1.44 μL microbubbles/kg/hour as per the FDA approved IND through an IV line in a peripheral vein. The total duration of contrast agent infusion is expected to range from 4 to 8 minutes, which includes a 2 min calibration period followed by 2-6 minutes of SHAPE acquisition (i.e., ultrasound imaging).

active comparator: SHAPE with Lumason

Up to 60 children (6-21 years of age) with a diagnosis of chronic liver disease, including some who will have portal hypertension who are followed at CHOP will be enrolled in this arm. A SHAPE measurement using the ultrasound contrast agent LUMASON® (sulfur hexafluoride lipid-type A microspheres) will be performed during a single visit. Two doses of 0.03 mL/kg (or 2.4 mL maximum) as per package labeling will be prepared and mixed with saline at a 1:10 dilution in a 50 ml bag of saline. The diluted preparation of Lumason will be through an IV line in a peripheral vein up to 4 mL/min using an infusion setup. The total duration of contrast agent infusion is expected to range from 4 to 8 minutes, which includes a 2 min calibration period followed by 2-6 minutes of SHAPE acquisition (i.e., ultrasound imaging).

experimental: Longitudinal SHAPE

SHAPE will be used to monitor subjects identified in the initial examination as having portal hypertension for up to 18 months. These subjects will undergo laboratory testing every 6 months as a part of their clinical standard of care. During these times the SHAPE examination will also be repeated using the same ultrasound contrast agent and infusion methodologies (including dosages) as during the initial study.

Interventions

SHAPE measurement using the ultrasound contrast agent Sonazoid (perfluorobutane microbubbles)

The ultrasound contrast agent will be infused thorough an IV line and SHAPE ultrasound imaging and data acquisition will be performed with a Logiq E10 (GE Medical Systems, Waukesha, WI) ultrasound scanner.

SHAPE measurement using the ultrasound contrast agent Lumason (sulfur hexafluoride lipid-type A microspheres)

The ultrasound contrast agent will be infused thorough an IV line and SHAPE ultrasound imaging and data acquisition will be performed with a Logiq E10 (GE Medical Systems, Waukesha, WI) ultrasound scanner.

Primary outcome measure

  • The rate (%) of adverse events that occur with Sonazoid compared to the current rate of adverse events that have been reported in the Lumason package insert for pediatric use (0.001%) [ Time Frame: 2 hours ]
  • Calibrated subharmonic microbubble signals (in dB) between the portal and hepatic veins will differentiate between the portal hypertension and non-portal hypertension groups with an accuracy of 94% [ Time Frame: 2 hours ]

Central Contacts and Locations

Central contacts

Morgan L Gabbert, MA

267-426-0820gabbertm@email.chop.edu

Locations

The Children's Hospital of Philadelphia

Recruiting

Philadelphia, Pennsylvania, United States, 19104

Contacts

Morgan L Gabbert, MA

267-426-0820gabbertm@email.chop.edu

Principal Investigator:

Sudha A Anupindi, MD

More Information

Sponsor

Thomas Jefferson University

Last update posted

Feb 11, 2025

Last verified

Jan, 2025

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by Thomas Jefferson University on 2025-02-11.