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Stima della pressione assistita subarmonica non invasiva dell'ipertensione portale; Rinnovo

29 settembre 2026 aggiornato da: Thomas Jefferson University

Stima della pressione assistita subarmonica non invasiva dell'ipertensione portale

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.

Panoramica dello studio

Stato

Reclutamento

Condizioni

Intervento / Trattamento

Descrizione dettagliata

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 di studio

Interventistico

Iscrizione (Stimato)

660

Fase

  • Fase 3

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Contatto studio

Backup dei contatti dello studio

Luoghi di studio

  • Stati Uniti
    • Pennsylvania
      • Philadelphia, Pennsylvania, Stati Uniti, 19104
      • Philadelphia, Pennsylvania, Stati Uniti, 19107
        • Reclutamento
        • Thomas Jefferson University, Dept of Radiology
        • Contatto:
        • Investigatore principale:
          • Flemming Forsberg, PhD
        • Sub-investigatore:
          • John R Eisenbrey, PhD
        • Sub-investigatore:
          • Kevin Anton, MD
        • Sub-investigatore:
          • Jonathan Fenkel, MD
        • Sub-investigatore:
          • Ji-Bin Liu, MD
        • Contatto:
  • Svizzera
      • Bern, Svizzera, 3010

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

18 anni e precedenti (Adulto, Adulto più anziano)

Accetta volontari sani

No

Sessi ammissibili allo studio

Tutto

Descrizione

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

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

  • Scopo principale: Diagnostico
  • Assegnazione: Non randomizzato
  • Modello interventistico: Assegnazione parallela
  • Mascheramento: Nessuno (etichetta aperta)

Armi e interventi

Gruppo di partecipanti / Arm
Intervento / Trattamento
Sperimentale: 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.
Droga: 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.

Altri nomi:
  • Sonazoide
Droga: 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.

Altri nomi:
  • Definitività
Sperimentale: 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.
Droga: 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.

Altri nomi:
  • Sonazoide
Sperimentale: 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.
Droga: 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.

Altri nomi:
  • Sonazoide
Sperimentale: 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.
Droga: 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.

Altri nomi:
  • Sonazoide

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Reproducibility of SHAPE liver pressure measurements
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Sponsor

Thomas Jefferson University

Collaboratori

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

Investigatori

  • Investigatore principale: Flemming Forsberg, PhD, Thomas Jefferson University

Pubblicazioni e link utili

La persona responsabile dell'inserimento delle informazioni sullo studio fornisce volontariamente queste pubblicazioni. Questi possono riguardare qualsiasi cosa relativa allo studio.

Pubblicazioni generali

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio (Effettivo)

28 novembre 2022

Completamento primario (Stimato)

28 febbraio 2028

Completamento dello studio (Stimato)

30 aprile 2028

Date di iscrizione allo studio

Primo inviato

13 giugno 2022

Primo inviato che soddisfa i criteri di controllo qualità

20 luglio 2022

Primo Inserito (Effettivo)

22 luglio 2022

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Effettivo)

2 ottobre 2026

Ultimo aggiornamento inviato che soddisfa i criteri QC

29 settembre 2026

Ultimo verificato

1 settembre 2026

Maggiori informazioni

Termini relativi a questo studio

Termini MeSH pertinenti aggiuntivi

Altri numeri di identificazione dello studio

  • 21F.1224
  • 2R01DK098526 (Sovvenzione/contratto NIH degli Stati Uniti)

Piano per i dati dei singoli partecipanti (IPD)

Hai intenzione di condividere i dati dei singoli partecipanti (IPD)?

SÌ

Descrizione del piano 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.

Periodo di condivisione IPD

After the completion of the study

Tipo di informazioni di supporto alla condivisione IPD

  • STUDIO_PROTOCOLLO
  • LINFA
  • ICF

Informazioni su farmaci e dispositivi, documenti di studio

Studia un prodotto farmaceutico regolamentato dalla FDA degli Stati Uniti

Sì

Studia un dispositivo regolamentato dalla FDA degli Stati Uniti

No

Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .

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