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Estimativa não invasiva da pressão assistida por subharmônicos da hipertensão portal; Renovação

29 de setembro de 2026 atualizado por: Thomas Jefferson University

Estimativa não invasiva da pressão assistida por subharmônicos da hipertensão portal

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.

Visão geral do estudo

Status

Recrutamento

Condições

Intervenção / Tratamento

Descrição detalhada

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.

Tipo de estudo

Intervencional

Inscrição (Estimado)

660

Estágio

  • Fase 3

Contactos e Locais

Esta seção fornece os detalhes de contato para aqueles que conduzem o estudo e informações sobre onde este estudo está sendo realizado.

Contato de estudo

Estude backup de contato

Locais de estudo

  • Estados Unidos
    • Pennsylvania
      • Philadelphia, Pennsylvania, Estados Unidos, 19104
      • Philadelphia, Pennsylvania, Estados Unidos, 19107
        • Recrutamento
        • Thomas Jefferson University, Dept of Radiology
        • Contato:
        • Investigador principal:
          • Flemming Forsberg, PhD
        • Subinvestigador:
          • John R Eisenbrey, PhD
        • Subinvestigador:
          • Kevin Anton, MD
        • Subinvestigador:
          • Jonathan Fenkel, MD
        • Subinvestigador:
          • Ji-Bin Liu, MD
        • Contato:
  • Suíça
      • Bern, Suíça, 3010

Critérios de participação

Os pesquisadores procuram pessoas que se encaixem em uma determinada descrição, chamada de critérios de elegibilidade. Alguns exemplos desses critérios são a condição geral de saúde de uma pessoa ou tratamentos anteriores.

Critérios de elegibilidade

Idades elegíveis para estudo

18 anos e mais velhos (Adulto, Adulto mais velho)

Aceita Voluntários Saudáveis

Não

Gêneros Elegíveis para o Estudo

Tudo

Descrição

Inclusion Criteria:

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.

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

Exclusion Criteria:

  • 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)
    • 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

Plano de estudo

Esta seção fornece detalhes do plano de estudo, incluindo como o estudo é projetado e o que o estudo está medindo.

Como o estudo é projetado?

Detalhes do projeto

  • Finalidade Principal: Diagnóstico
  • Alocação: Não randomizado
  • Modelo Intervencional: Atribuição Paralela
  • Mascaramento: Nenhum (rótulo aberto)

Armas e Intervenções

Grupo de Participantes / Braço
Intervenção / Tratamento
Experimental: Reproducibility - Cohort 1

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.
Medicamento: 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.

Outros nomes:
  • Sonazóide
Medicamento: SHAPE measurement (Definity ultrasoud contrast agent)

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.

Outros nomes:
  • Definição
Experimental: HCC monitoring - Cohort 2

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.
Medicamento: 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.

Outros nomes:
  • Sonazóide
Experimental: New β-blockers - Cohort 3

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.
Medicamento: 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.

Outros nomes:
  • Sonazóide
Experimental: Ccreening for varices - Cohort 4

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.
Medicamento: 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.

Outros nomes:
  • Sonazóide

O que o estudo está medindo?

Medidas de resultados primários

Medida de resultado
Descrição da medida
Prazo
Reproducibility of SHAPE liver pressure measurements
Prazo: 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.
during procedure
Number of subjects who develop ascites during follow-up
Prazo: 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).
up to 18 months
Number of subjects who experience clinical decompensation events (including the development of variceal bleeding) during follow-up
Prazo: 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.
up to 18 months
Number of subjects who present with esophageal or gastric varices on endoscopy
Prazo: 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
baseline

Colaboradores e Investigadores

É aqui que você encontrará pessoas e organizações envolvidas com este estudo.

Patrocinador

Thomas Jefferson University

Colaboradores

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

Investigadores

  • Investigador principal: Flemming Forsberg, PhD, Thomas Jefferson University

Publicações e links úteis

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Publicações Gerais

Datas de registro do estudo

Essas datas acompanham o progresso do registro do estudo e os envios de resumo dos resultados para ClinicalTrials.gov. Os registros do estudo e os resultados relatados são revisados ​​pela National Library of Medicine (NLM) para garantir que atendam aos padrões específicos de controle de qualidade antes de serem publicados no site público.

Datas Principais do Estudo

Início do estudo (Real)

28 de novembro de 2022

Conclusão Primária (Estimado)

28 de fevereiro de 2028

Conclusão do estudo (Estimado)

30 de abril de 2028

Datas de inscrição no estudo

Enviado pela primeira vez

13 de junho de 2022

Enviado pela primeira vez que atendeu aos critérios de CQ

20 de julho de 2022

Primeira postagem (Real)

22 de julho de 2022

Atualizações de registro de estudo

Última Atualização Postada (Real)

2 de outubro de 2026

Última atualização enviada que atendeu aos critérios de controle de qualidade

29 de setembro de 2026

Última verificação

1 de setembro de 2026

Mais Informações

Termos relacionados a este estudo

Termos MeSH relevantes adicionais

Outros números de identificação do estudo

  • 21F.1224
  • 2R01DK098526 (Concessão/Contrato do NIH dos EUA)

Plano para dados de participantes individuais (IPD)

Planeja compartilhar dados de participantes individuais (IPD)?

SIM

Descrição do plano IPD

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.

Prazo de Compartilhamento de IPD

After the completion of the study

Tipo de informação de suporte de compartilhamento de IPD

  • PROTOCOLO DE ESTUDO
  • SEIVA
  • CIF

Informações sobre medicamentos e dispositivos, documentos de estudo

Estuda um medicamento regulamentado pela FDA dos EUA

Sim

Estuda um produto de dispositivo regulamentado pela FDA dos EUA

Não

Essas informações foram obtidas diretamente do site clinicaltrials.gov sem nenhuma alteração. Se você tiver alguma solicitação para alterar, remover ou atualizar os detalhes do seu estudo, entre em contato com register@clinicaltrials.gov. Assim que uma alteração for implementada em clinicaltrials.gov, ela também será atualizada automaticamente em nosso site .

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