Chronic Liver DiseasesNCT02653846
Correlation of Liver and Spleen Stiffness by RT-2D-SWE and Severity of Portal Hypertension by HVPG
An observational study of Chronic Liver Diseases, run by University Hospital Dubrava at 1 site in Croatia.
Trial summary
Portal hypertension (PH) results from the increase of portal flow resistance in fibrotic tissue of the liver in patients with chronic liver diseases, leading to complications such as varices formation and variceal bleeding, ascites formation, spleenomegaly and hypersplenismus, systemic haemodynamic disorders and… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Liver Diseases
- What is being tested?
- RT-2D-SWE measurement and HVPG measurement
- Type of treatment
- Surgery or procedure
- How many people
- 50 participants
- Where
- 1 siteCroatia
- Study dates
- Jun 2015to Jun 2022
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: outpatients and inpatients in a tertiary care hospital 1) with suspicion of having compensated advanced chronic liver disease (cACLD) as assessed by transabdominal ultrasound, laboratory findings, FIB-4 and/or APRI score, and/or LS measurements by TE; 2) patients with chronic liver disease in whom any extrahepatic surgical procedure is planned and in whom it was not possible to exclude cACLD and/or portal hypertension based on non-invasive procedures only; 3) patients with HCC or other liver tumors on the ground of presumed liver cirrhosis who are under consideration for surgical resection, in whom HVPG is performed in order to reliably exclude clinically significant portal hypertension
Who may be able to join
- patients with suspicion of having cACLD as assessed by transabdominal ultrasound, laboratory findings, FIB-4 and/or APRI score, and/or LS measurements
- patients with chronic liver disease in whom any extrahepatic surgical procedure is planned and in whom it was not possible to exclude cACLD and/or portal hypertension based on non-invasive procedures only
- patients with HCC or other liver tumors on the ground of presumed liver cirrhosis who are under consideration for surgical resection, in whom HVPG is performed in order to reliably exclude clinically significant portal hypertension
- compliance to the study protocol
- signed approval for the diagnostic ultrasound with SWE™ and for transjugular liver biopsy and HVPG measurement
Who cannot join
- elevated alanine aminotransferase (ALT) values > 5 x upper limit of normal (ULN)
- obstructive jaundice
- congestive heart failure
- sepsis
- thrombosis of right jugular vein
- thrombosis of hepatic veins
Show all 10Show fewer
- hydatid cyst
- cholangitis
- absence of cooperation
- pregnancy
Trial locations and contacts
1 site in 1 country.
Ivica Grgurevic, MD, PhD contact
Tomislav Bokun, MD contact
Croatia1 site, 1 recruiting
- Recruiting
University Hospital Dubrava
Zagreb, 10040
Ivica Grgurevic, MD, PhD, ivica.grgurevic@zg.htnet.hr
Ivica Grgurevic, MD, PhD
About this study
Official title: Correlation of Liver and Spleen Stifness as Assesed by Real Time 2-Dimensional Shear Wave Elastography With Severity of Portal Hypertension and Clinical Outcomes in Patients With Compensated Advanced Chronic Liver Disease
Portal hypertension (PH) results from the increase of portal flow resistance in fibrotic tissue of the liver in patients with chronic liver diseases, leading to complications such as varices formation and variceal bleeding, ascites formation, spleenomegaly and hypersplenismus, systemic haemodynamic disorders and porto-systemic shunts formation. Early detection of PH in patients with chronic liver diseases is clinically important as it should change patient management in order to prevent the formation/onset or recurrence of PH complications. Hepatic venous pressure gradient (HVPG) measurement is the gold standard for the assessment of the severity of PH. However, it is an invasive method with its risks, and relatively costly. On the other hand transient elastography (TE) emerged as a non-invasive, easy, safe and low cost method with the potential to assess the severity of PH, as liver stiffness (LS) and spleen stiffens (SS) measured by TE showed very good correlation with HVPG. Real-time 2D shear wave elastography (RT-2D-SWE) is an ultrasound elastography method reliable for non-invasive assessment of fibrosis stage especially in chronic viral hepatitis, but only preliminary data exist on the correlation of RT-2D-SWE measured LS/SS with and HVPG. In this study we hypothesized that LS and SS measured by RT-2D-SWE correlate with HVPG enabling RT-2D-SWE to be used for the assessment of severity of PH. The primary aim of this study is to analyse correlation between LS and SS as assessed by RT-2D-SWE and TE with the grade of portal hypertension as assessed by HVPG. The secondary aims are: 1) to analyse clinical outcomes of these patients in order to determine if LS and/or SS as assessed by RT-2D-SWE might predict adverse outcomes (liver decompensation, death or HCC development), and 2) to compare clinical performance (AUC) of RT-2D-SWE and TE for the assessment of the PH severity as well as for predicting clinical outcomes. Patients with suspicion of having compensated advanced chronic liver disease (cACLD) as assesed by non-invasive methods (transabdominal ultrasound, laboratory findings, FIB-4 and APRI score, and LS measurements by TE), will be included. Since positive predictive value of non-invasive methods for cirrhosis is generally not very reliable, these patients will be offered transjugular liver biopsy and HVPG measurements as gold-standard methods to define the stage of liver disease and severity of PH. These patients will undergo LS and SS measurements by RT-2D-SWE on Aixplorer SuperSonic Imagine ultrasound system and HVPG measurements as well, with transjugular liver biopsy performed during the same session. After SWE™ and HVPG measurement, 5-year follow-up is planned, including standard surveillance: laboratory findings, transabdominal US every six months and upper-GI endoscopy according to relevant guidelines, as well as treatment according to relevant guidelines as indicated: beta blockers, endoscopic variceal ligation, etiologic treatment and dietary measures. Appropriate statistical analysis will be undertaken after the enrollment period, as well as after follow-up period.
- Conditions
- Chronic Liver Diseases
- Being tested
- RT-2D-SWE measurement, HVPG measurement
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RT-2D-SWE measurementProcedure or surgery
measurement of liver and spleen stiffness by ultrasound real-time 2D shear wave elastography (SWE™)
HVPG measurementProcedure or surgery
assessment of portal hypertension assessed by hepatic venous pressure gradient measurement
What is being measured
The primary outcome is the main question the study is designed to answer.
liver and spleen stiffness
liver and spleen stiffness expressed in kPa, measured by real-time 2D shear wave elastography (SWE™) on Aixplorer® ultrasound machine from SuperSonic Imagine, Aix-en-Provence, France
Measured: at the time of enrollment
HVPG
severity of portal hypertension assessed by hepatic venous pressure gradient (HVPG) measurements
Measured: within one week of enrollment
Secondary outcomes (3)
development of hepatic decompensation
hepatic decompensation defined as: onset of icterus, onset of ascites diagnosed by transabdominal ultrasonud or CT scan, onset of portal encephalophaty diagnosed clinically, episode of variceal bleeding confirmed endoscopically
Measured: during follow-up period of 5 years
Hepatocellular carcinoma (HCC) development
conformed by contrast MDCT and/or MRI and/or tumor biopsy
Measured: during follow-up period of 5 years
mortality
Measured: during follow-up period of 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jan 2016 (estimated)
- Study startJun 2015
- Primary completionJun 2017 (estimated)
- Study completionJun 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Chronic Liver DiseasesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital Dubrava
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ivica Grgurevic, MD, University Hospital Dubrava
- Investigators
- Ivica Grgurevic, MD, PhD, Principal investigator, University Hospital Dubrava
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02653846
- Sponsor's protocol ID
- KBD-IG-LS/SSvsHVPG
- Status last verified
- Sep 2016
- First submitted
- 31 Dec 2015
- Last updated
- 8 Sep 2016
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Berzigotti A, Seijo S, Arena U, Abraldes JG, Vizzutti F, Garcia-Pagan JC, Pinzani M, Bosch J. Elastography, spleen size, and platelet count identify portal hypertension in patients with compensated cirrhosis. Gastroenterology. 2013 Jan;144(1):102-111.e1. doi: 10.1053/j.gastro.2012.10.001. Epub 2012 Oct 8.
PubMed 23058320Augustin S, Millan L, Gonzalez A, Martell M, Gelabert A, Segarra A, Serres X, Esteban R, Genesca J. Detection of early portal hypertension with routine data and liver stiffness in patients with asymptomatic liver disease: a prospective study. J Hepatol. 2014 Mar;60(3):561-9. doi: 10.1016/j.jhep.2013.10.027. Epub 2013 Nov 6.
PubMed 24211744Vergniol J, Foucher J, Terrebonne E, Bernard PH, le Bail B, Merrouche W, Couzigou P, de Ledinghen V. Noninvasive tests for fibrosis and liver stiffness predict 5-year outcomes of patients with chronic hepatitis C. Gastroenterology. 2011 Jun;140(7):1970-9, 1979.e1-3. doi: 10.1053/j.gastro.2011.02.058. Epub 2011 Mar 2.
PubMed 21376047Colecchia A, Montrone L, Scaioli E, Bacchi-Reggiani ML, Colli A, Casazza G, Schiumerini R, Turco L, Di Biase AR, Mazzella G, Marzi L, Arena U, Pinzani M, Festi D. Measurement of spleen stiffness to evaluate portal hypertension and the presence of esophageal varices in patients with HCV-related cirrhosis. Gastroenterology. 2012 Sep;143(3):646-654. doi: 10.1053/j.gastro.2012.05.035. Epub 2012 May 27.
PubMed 22643348Colecchia A, Colli A, Casazza G, Mandolesi D, Schiumerini R, Reggiani LB, Marasco G, Taddia M, Lisotti A, Mazzella G, Di Biase AR, Golfieri R, Pinzani M, Festi D. Spleen stiffness measurement can predict clinical complications in compensated HCV-related cirrhosis: a prospective study. J Hepatol. 2014 Jun;60(6):1158-64. doi: 10.1016/j.jhep.2014.02.024. Epub 2014 Mar 6.
PubMed 24607624Behrens G, Ferral H. Transjugular liver biopsy. Semin Intervent Radiol. 2012 Jun;29(2):111-7. doi: 10.1055/s-0032-1312572.
PubMed 23729981Dohan A, Guerrache Y, Boudiaf M, Gavini JP, Kaci R, Soyer P. Transjugular liver biopsy: indications, technique and results. Diagn Interv Imaging. 2014 Jan;95(1):11-5. doi: 10.1016/j.diii.2013.08.009. Epub 2013 Sep 3.
PubMed 24007769
Study at a glance
From the registry record, last updated by the sponsor on 8 Sep 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Correlation of Liver and Spleen Stifness as Assesed by Real Time 2-Dimensional Shear Wave Elastography With Severity of Portal Hypertension and Clinical Outcomes in Patients With Compensated Advanced Chronic Liver Disease
- ClinicalTrials.gov ID
- NCT02653846
- Acronym / sponsor ID
- KBD-IG-LS/SSvsHVPG
- Conditions
- Chronic Liver Diseases
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- University Hospital DubravaUniversity, hospital or other
- Study start
- Jun 2015
- Primary completion
- Jun 2017 (estimated)
- Study completion
- Jun 2022 (estimated)
- First posted
- 12 Jan 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Portal hypertension (PH) results from the increase of portal flow resistance in fibrotic tissue of the liver in patients with chronic liver diseases, leading to complications such as varices formation and variceal bleeding, ascites formation, spleenomegaly and hypersplenismus, systemic haemodynamic disorders and porto-systemic shunts formation. Early detection of PH in patients with chronic liver diseases is clinically important as it should change patient management in order to prevent the formation/onset or recurrence of PH complications. Hepatic venous pressure gradient (HVPG) measurement is the gold standard for the assessment of the severity of PH. However, it is an invasive method with its risks, and relatively costly. On the other hand transient elastography (TE) emerged as a non-invasive, easy, safe and low cost method with the potential to assess the severity of PH, as liver stiffness (LS) and spleen stiffens (SS) measured by TE showed very good correlation with HVPG. Real-time 2D shear wave elastography (RT-2D-SWE) is an ultrasound elastography method reliable for non-invasive assessment of fibrosis stage especially in chronic viral hepatitis, but only preliminary data exist on the correlation of RT-2D-SWE measured LS/SS with and HVPG. In this study we hypothesized that LS and SS measured by RT-2D-SWE correlate with HVPG enabling RT-2D-SWE to be used for the assessment of severity of PH. The primary aim of this study is to analyse correlation between LS and SS as assessed by RT-2D-SWE and TE with the grade of portal hypertension as assessed by HVPG. The secondary aims are: 1) to analyse clinical outcomes of these patients in order to determine if LS and/or SS as assessed by RT-2D-SWE might predict adverse outcomes (liver decompensation, death or HCC development), and 2) to compare clinical performance (AUC) of RT-2D-SWE and TE for the assessment of the PH severity as well as for predicting clinical outcomes. Patients with suspicion of having compensated advanced chronic liver disease (cACLD) as assesed by non-invasive methods (transabdominal ultrasound, laboratory findings, FIB-4 and APRI score, and LS measurements by TE), will be included. Since positive predictive value of non-invasive methods for cirrhosis is generally not very reliable, these patients will be offered transjugular liver biopsy and HVPG measurements as gold-standard methods to define the stage of liver disease and severity of PH. These patients will undergo LS and SS measurements by RT-2D-SWE on Aixplorer SuperSonic Imagine ultrasound system and HVPG measurements as well, with transjugular liver biopsy performed during the same session. After SWE™ and HVPG measurement, 5-year follow-up is planned, including standard surveillance: laboratory findings, transabdominal US every six months and upper-GI endoscopy according to relevant guidelines, as well as treatment according to relevant guidelines as indicated: beta blockers, endoscopic variceal ligation, etiologic treatment and dietary measures. Appropriate statistical analysis will be undertaken after the enrollment period, as well as after follow-up period.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- outpatients and inpatients in a tertiary care hospital 1) with suspicion of having compensated advanced chronic liver disease (cACLD) as assessed by transabdominal ultrasound, laboratory findings, FIB-4 and/or APRI score, and/or LS measurements by TE; 2) patients with chronic liver disease in whom any extrahepatic surgical procedure is planned and in whom it was not possible to exclude cACLD and/or portal hypertension based on non-invasive procedures only; 3) patients with HCC or other liver tumors on the ground of presumed liver cirrhosis who are under consideration for surgical resection, in whom HVPG is performed in order to reliably exclude clinically significant portal hypertension
Key inclusion criteria (5 listed)
- patients with suspicion of having cACLD as assessed by transabdominal ultrasound, laboratory findings, FIB-4 and/or APRI score, and/or LS measurements
- patients with chronic liver disease in whom any extrahepatic surgical procedure is planned and in whom it was not possible to exclude cACLD and/or portal hypertension based on non-invasive procedures only
- patients with HCC or other liver tumors on the ground of presumed liver cirrhosis who are under consideration for surgical resection, in whom HVPG is performed in order to reliably exclude clinically significant portal hypertension
- compliance to the study protocol
- signed approval for the diagnostic ultrasound with SWE™ and for transjugular liver biopsy and HVPG measurement
Key exclusion criteria (10 listed)
- elevated alanine aminotransferase (ALT) values > 5 x upper limit of normal (ULN)
- obstructive jaundice
- congestive heart failure
- sepsis
- thrombosis of right jugular vein
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RT-2D-SWE measurementmeasurement of liver and spleen stiffness by ultrasound real-time 2D shear wave elastography (SWE™) | Procedure or surgery | – |
| HVPG measurementassessment of portal hypertension assessed by hepatic venous pressure gradient measurement | Procedure or surgery | – |
Primary outcome
liver and spleen stiffness
Time frame: at the time of enrollment
liver and spleen stiffness expressed in kPa, measured by real-time 2D shear wave elastography (SWE™) on Aixplorer® ultrasound machine from SuperSonic Imagine, Aix-en-Provence, France
HVPG
Time frame: within one week of enrollment
severity of portal hypertension assessed by hepatic venous pressure gradient (HVPG) measurements
3 secondary outcomes
development of hepatic decompensation
Time frame: during follow-up period of 5 years
Hepatocellular carcinoma (HCC) development
Time frame: during follow-up period of 5 years
mortality
Time frame: during follow-up period of 5 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Sep 2016.
- Background: PubMed 23058320Berzigotti A, Seijo S, Arena U, Abraldes JG, Vizzutti F, Garcia-Pagan JC, Pinzani M, Bosch J. Elastography, spleen size, and platelet count identify portal hypertension in patients with compensated cirrhosis. Gastroenterology. 2013 Jan;144(1):102-111.e1. doi: 10.1053/j.gastro.2012.10.001. Epub 2012 Oct 8.
- Background: PubMed 24211744Augustin S, Millan L, Gonzalez A, Martell M, Gelabert A, Segarra A, Serres X, Esteban R, Genesca J. Detection of early portal hypertension with routine data and liver stiffness in patients with asymptomatic liver disease: a prospective study. J Hepatol. 2014 Mar;60(3):561-9. doi: 10.1016/j.jhep.2013.10.027. Epub 2013 Nov 6.
- Background: PubMed 21376047Vergniol J, Foucher J, Terrebonne E, Bernard PH, le Bail B, Merrouche W, Couzigou P, de Ledinghen V. Noninvasive tests for fibrosis and liver stiffness predict 5-year outcomes of patients with chronic hepatitis C. Gastroenterology. 2011 Jun;140(7):1970-9, 1979.e1-3. doi: 10.1053/j.gastro.2011.02.058. Epub 2011 Mar 2.
- Background: PubMed 22643348Colecchia A, Montrone L, Scaioli E, Bacchi-Reggiani ML, Colli A, Casazza G, Schiumerini R, Turco L, Di Biase AR, Mazzella G, Marzi L, Arena U, Pinzani M, Festi D. Measurement of spleen stiffness to evaluate portal hypertension and the presence of esophageal varices in patients with HCV-related cirrhosis. Gastroenterology. 2012 Sep;143(3):646-654. doi: 10.1053/j.gastro.2012.05.035. Epub 2012 May 27.
- Background: PubMed 24607624Colecchia A, Colli A, Casazza G, Mandolesi D, Schiumerini R, Reggiani LB, Marasco G, Taddia M, Lisotti A, Mazzella G, Di Biase AR, Golfieri R, Pinzani M, Festi D. Spleen stiffness measurement can predict clinical complications in compensated HCV-related cirrhosis: a prospective study. J Hepatol. 2014 Jun;60(6):1158-64. doi: 10.1016/j.jhep.2014.02.024. Epub 2014 Mar 6.
- Background: PubMed 23729981Behrens G, Ferral H. Transjugular liver biopsy. Semin Intervent Radiol. 2012 Jun;29(2):111-7. doi: 10.1055/s-0032-1312572.
- Background: PubMed 24007769Dohan A, Guerrache Y, Boudiaf M, Gavini JP, Kaci R, Soyer P. Transjugular liver biopsy: indications, technique and results. Diagn Interv Imaging. 2014 Jan;95(1):11-5. doi: 10.1016/j.diii.2013.08.009. Epub 2013 Sep 3.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ivica Grgurevic, MD, PhD contact
Tomislav Bokun, MD contact
Ivica Grgurevic, MD, PhD principal investigator
University Hospital Dubrava
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Chronic Liver Diseases, run by University Hospital Dubrava at 1 site in Croatia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 8 Sep 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Croatia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Ivica Grgurevic, MD, PhD (ivica.grgurevic@zg.htnet.hr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
liver and spleen stiffness (time frame: at the time of enrollment). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02653846, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Sep 2016.