SHAPE of Portal Hypertension in Children
Ikke-invasiv subharmonisk støttet trykkestimering av portalhypertensjon hos barn
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.
Studieoversikt
Status
Forhold
Studietype
Registrering (Faktiske)
Fase
- Fase 2
Kontakter og plasseringer
Studiesteder
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Pennsylvania
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Philadelphia, Pennsylvania, Forente stater, 19104
- The Children's Hospital of Philadelphia
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Deltakelseskriterier
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
Tar imot friske frivillige
Kjønn som er kvalifisert for studier
Beskrivelse
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
Studieplan
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Diagnostisk
- Tildeling: Randomisert
- Intervensjonsmodell: Parallell tildeling
- Masking: Ingen (Open Label)
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
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Eksperimentell: 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). |
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. |
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Aktiv komparator: 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). |
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. |
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Eksperimentell: 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. |
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. 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. |
Hva måler studien?
Primære resultatmål
Resultatmål |
Tidsramme |
|---|---|
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Frekvensen (%) av bivirkninger som oppstår med Sonazoid sammenlignet med gjeldende forekomst av bivirkninger som er rapportert i pakningsvedlegget til Lumason for pediatrisk bruk (0,001 %)
Tidsramme: 2 timer
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2 timer
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Kalibrerte subharmoniske mikroboblesignaler (i dB) mellom portal- og levervenene vil skille mellom gruppene portalhypertensjon og ikke-portalhypertensjon med en nøyaktighet på 94 %
Tidsramme: 2 timer
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2 timer
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Sekundære resultatmål
Resultatmål |
Tidsramme |
|---|---|
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Endringer i kalibrerte subharmoniske mikroboblesignaler (i dB) mellom portal- og levervenene over tid vil forutsi utviklingen av komplikasjoner av portalhypertensjon (variceal blødning, ascites, hepatopulmonal syndrom, etc)
Tidsramme: i gjennomsnitt 18 måneder
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i gjennomsnitt 18 måneder
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Kalibrerte subharmoniske mikroboblesignaler (i dB) mellom portal- og levervenene og leverfibrosestadiet (på en skala fra 0-4 bestemt ved leverbiopsi) vil korrelere med en p<0,05
Tidsramme: 2 timer
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2 timer
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Sammenlign de kalibrerte subharmoniske mikroboblesignalene (i dB) mellom portal- og levervenene oppnådd med henholdsvis Lumason og Sonazoid for deres evne til å skille mellom portalhypertensjons- og ikke-portalhypertensjonsgruppene
Tidsramme: 2 timer
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2 timer
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Sammenlign kalibrerte subharmoniske mikroboblesignaler (i dB) mellom portal- og levervenene med skjærbølgeelastografiverdier (i m/s) ved hjelp av regresjonsanalyse
Tidsramme: 2 timer
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2 timer
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Samarbeidspartnere og etterforskere
Sponsor
Samarbeidspartnere
Etterforskere
- Hovedetterforsker: Sudha A Anupindi, MD, Children's Hospital of Philadelphia
- Hovedetterforsker: Flemming Forsberg, PhD, Thomas Jefferson University
Publikasjoner og nyttige lenker
Generelle publikasjoner
- 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.
- 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.
Studierekorddatoer
Studer hoveddatoer
Studiestart (Faktiske)
Primær fullføring (Faktiske)
Studiet fullført (Faktiske)
Datoer for studieregistrering
Først innsendt
Først innsendt som oppfylte QC-kriteriene
Først lagt ut (Faktiske)
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
Siste oppdatering sendt inn som oppfylte QC-kriteriene
Sist bekreftet
Mer informasjon
Begreper knyttet til denne studien
Ytterligere relevante MeSH-vilkår
Andre studie-ID-numre
- 20F.728
- R01DK118964 (U.S. NIH-stipend/kontrakt)
Plan for individuelle deltakerdata (IPD)
Planlegger du å dele individuelle deltakerdata (IPD)?
IPD-planbeskrivelse
Data generated from the proposed study will be shared to make the results available to the scientific community.
Presentations at national scientific meetings.
Lectures.
Post-graduate training.
Approximately 12 months after the completion of the trial (when the main manuscript has been published) individual researchers can contact the PIs and request the final, complete data-set from this trial without any protected health information
IPD-delingstidsramme
Approximately 12 months after the completion of the trial when the main manuscript has been published
Tilgangskriterier for IPD-deling
On an individual basis - contact the PIs
IPD-deling Støtteinformasjonstype
- STUDY_PROTOCOL
- SEVJE
- ICF
Legemiddel- og utstyrsinformasjon, studiedokumenter
Studerer et amerikansk FDA-regulert medikamentprodukt
Studerer et amerikansk FDA-regulert enhetsprodukt
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