Clinical trial NCT04720456: SHAPE of Portal Hypertension in Children
Official title: Noninvasive Subharmonic Aided Pressure Estimation of Portal Hypertension in Children
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Hypertension, Portal
Lead sponsor: Thomas Jefferson University
Sponsor class: OTHER
Collaborators: name: Children's Hospital of Philadelphia
name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2021-01-22
Enrollment: 120
Sex: ALL
Minimum age (years): 6
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A prospective randomized cohort study with a longitudinal arm. There will be 2 cohorts.
Primary purpose: DIAGNOSTIC

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.


Eligibility criteria: 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

Primary outcomes:
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%)
timeFrame: 2 hours
measure: 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%
timeFrame: 2 hours
Secondary outcomes:
measure: Changes in calibrated subharmonic microbubble signals (in dB) between the portal and hepatic veins over time will predict the development of complications of portal hypertension (variceal bleeding, ascites, hepatopulmonary syndrome, etc)
timeFrame: on average 18 months
measure: Calibrated subharmonic microbubble signals (in dB) between the portal and hepatic veins and liver fibrosis stage (on a scale from 0-4 as determined by liver biopsy) will correlate with a p<0.05
timeFrame: 2 hours
measure: Compare the calibrated subharmonic microbubble signals (in dB) between the portal and hepatic veins obtained with Lumason and Sonazoid, respectively, for their ability to differentiate between the portal hypertension and non-portal hypertension groups
timeFrame: 2 hours
measure: Compare calibrated subharmonic microbubble signals (in dB) between the portal and hepatic veins to shear wave elastography values (in m/s) using regression analysis
timeFrame: 2 hours
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: The Children's Hospital of Philadelphia
state: Pennsylvania
Study officials:
affiliation: Thomas Jefferson University
name: Flemming Forsberg, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Children's Hospital of Philadelphia
name: Sudha A Anupindi, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.