Portal HypertensionNCT02508298
Surrogate Markers of Portal Pressure
A study testing HVPG, Indocyanine Green Retention test and Liver stiffness measurement in people with Portal Hypertension and Cirrhosis, run by VA Connecticut Healthcare System at 2 sites in United States.
Trial summary
This is a prospective longitudinal study that will evaluate if changes (pre and post therapy) in indocyanine green (ICG) retention test and liver stiff ness (LS) and spleen stiffness (SS) as measured by acoustic radiofrequency impulse (ARFI) correlate with changes in portal pressure as determined by the hepatic vein… Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Portal Hypertension, Cirrhosis
- What is being tested?
- HVPG, Indocyanine Green Retention test and Liver stiffness measurement
- Type of treatment
- Injection or infusion, Medical device, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 41 participants
- Where
- 2 sitesUnited States
- Study dates
- Apr 2014to Jul 2019
- Phase
- Interventional
- 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 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18-85
- HCV infection (HCV-RNA positive)
- Compensated cirrhosis will be defined histologically and/or clinically (presence of compatible lab findings (platelet count ≤ 150,000, total bilirubin ≥ 2, serum albumin ≤ 3.5, INR ≥ 1.2) PLUS compatible physical exam features (cutaneous stigmata, gynecomastia in men, or splenomegaly) OR compatible radiological findings (nodular liver surface, splenomegaly, and/or collaterals). (The ultimate confirmation of the diagnosis of cirrhosis will be a baseline HVPG > 5 mmHg)
- Planned anti-HCV therapy in the next 3 months
Who cannot join
- Any clinically-evident complication of cirrhosis that defines decompensation : jaundice, ascites, variceal hemorrhage, overt hepatic encephalopathy)
- Hepatocellular carcinoma
- Co-infection with HBV or HIV
- Ongoing alcohol abuse
- Occlusive portal thrombosis,
- Presence of comorbid conditions conferring a life expectancy<1 year, history of allergy to iodides, pregnancy
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Yale-New Haven Hospital
New Haven, Connecticut, 06511
VA Connecticut Healthcare System
West Haven, Connecticut, 06516
About this study
Official title: Surrogate Markers of Portal Pressure and Changes in Portal Pressure in Patients With Compensated Cirrhosis Undergoing Anti-viral Therapy
This is a prospective longitudinal study that will evaluate if changes (pre and post therapy) in indocyanine green (ICG) retention test and liver stiff ness (LS) and spleen stiffness (SS) as measured by acoustic radiofrequency impulse (ARFI) correlate with changes in portal pressure as determined by the hepatic vein pressure gradient (HVPG) in patients with compensated hepatitis C virus (HCV) cirrhosis undergoing antiviral therapy.
Read the detailed description
Subjects will be recruited from the outpatient setting of the West Haven VA Medical Center and the Yale Liver Clinic. Subjects between 18-85 years of age with compensated cirrhosis due to chronic hepatitis C virus (HCV) infection who will be starting anti-viral therapy to treat HCV within the next 3 months will be eligible for this study. 33 subjects (assuming 10% loss to follow-up) will be recruited and their participation will last from 6-12 months. The expected duration of the study is 2 years.
The primary end point of the study is to correlate the change (from baseline to after completing anti-HCV therapy) in ICG retention test, LS and SS as measured by ARFI with HVPG. After consent has been obtained, subjects will undergo ICG retention test, ARFI imaging and HVPG measurements before and after HCV therapy. Blood samples, demographic and clinical data will be collected before and after HCV therapy. Correlations between changes in HVPG and changes in ICG, LS and SS will be assessed. With 30 patients , we will have 80% power to perform a hypothesis test of the Pearson correlation assuming an observed correlation of 0.70 and a two-sided type I error rate of 0.05.
- Conditions
- Portal Hypertension, Cirrhosis
- Being tested
- HVPG, Indocyanine Green Retention test, Liver stiffness measurement, Spleen stiffness measurement
- Keywords
- ICG, ARFI, portal hypertension, cirrhosis, diagnostic study
- Medical subject headings
- Hypertension, Portal, Fibrosis, Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HVPGProcedure or surgery
Also called Hepatic Venous Portal Gradient
HVPG will be performed by placing a placing a 7F venous catheter into a supra-hepatic vein and then advancing a 5F balloon-tipped catheter into the right hepatic vein. Wedged hepatic venous pressure (WHVP) and free hepatic venous pressure (FHVP) will be measured by connection to an external transducer and polygraph (PowerLab, ADInstruments Inc., Colorado Springs, CO). After inflating the balloon catheter, adequacy of the occlusion will be established by injection of a small amount of radiologic contrast medium. Hepatic Venous Pressure gradient (HVPG) will be calculated as the difference between WHVP and FHVP.
Indocyanine Green Retention testDrug
Also called ICG test
As decribed in arm descriptions
Liver stiffness measurementDevice
Also called LS
As decribed in arm descriptions; perfromed by ARFI
Spleen stiffness measurementDevice
Also called SS
As decribed in arm descriptions; performed by ARFI
| Study group | Role | What they receive |
|---|---|---|
| Indocyanine green retention test | Active comparator | A baseline venous sample of 5 ml of venous will be drawn for pre-infusion measurement. Under sterile conditions 0.5 mg/kg body weight of ICG will be injected into vein. Further blood samples (5 ml each) will be collected at 5, 10, 15 and 20 minute intervals after the injection from a peripheral vein in the opposite arm using another intravenous catheter. After serum is separated by centrifugation, optical densities will be measured at 804 nm using a calibrated method for measurement of ICG level s. ICG retention at 15 minutes and elimination rate constant will be calculated by fitting the serum disappearance curve to a single exponential decay equation.This will be compared to portal pressure measured by Hepatic Venous Portal Gradient (HVPG). Receives: Procedure: HVPG; Drug: Indocyanine Green Retention test |
| Liver stiffness measurement | Active comparator | ARFI measurements of the liver will be obtained using a standard ultrasound probe. The patient will be lying on his back and will be asked to hold his/her breath for 2-5 seconds during measurements.These will be compared to portal pressure measured by Hepatic Venous Portal Gradient (HVPG). Receives: Procedure: HVPG; Device: Liver stiffness measurement |
| Spleen stiffness measurement | Active comparator | ARFI measurements of the spleen will be obtained using a standard ultrasound probe. The patient will be lying on his back and will be asked to hold his/her breath for 2-5 seconds during measurements.These will be compared to portal pressure measured by Hepatic Venous Portal Gradient (HVPG). Receives: Procedure: HVPG; Device: Spleen stiffness measurement |
What is being measured
The primary outcome is the main question the study is designed to answer.
Indocyanine Green before and after treatment of hepatitis c
Indocyanine Green will be obtained , this will be conducted before and after treatment for hepatitis c and is measured in mg/dl
Measured: 2 years
Secondary outcomes (3)
Spleen stiffness before and after treatment of hepatitis c
Spleen stiffness will be obtained by ARFI, this will be conducted before and after treatment for hepatitis c and is measured in m/sec
Measured: 2 years
Liver stiffness before and after treatment of hepatitis c
Liver stiffness will be obtained by ARFI, this will be conducted before and after treatment for hepatitis c and is measured in m/sec
Measured: 2 years
Hepatic venous pressure gradient before and after treatment of hepatitis c
Hepatic venous pressure gradient would be obtained by catheterization of the hepatic vein, this will be conducted before and after treatment for hepatitis c and is measured in mmHg
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jul 2015 (estimated)
- Study startApr 2014
- Primary completionJul 2018
- Study completionJul 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Portal HypertensionStudies 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 41 participants (actual)
Sponsor and investigators
- Lead sponsor
- VA Connecticut Healthcare System
- Sponsor type
- US federal agency
- Responsible party
- Sponsor
- Investigators
- Guadalupe Garcia-Tsao, MD, Principal investigator, VA Connecticut Healthcare System
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02508298
- Sponsor's protocol ID
- GGT0037
- Status last verified
- Nov 2019
- First submitted
- 9 Jan 2015
- Last updated
- 25 Nov 2019
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Surrogate Markers of Portal Pressure and Changes in Portal Pressure in Patients With Compensated Cirrhosis Undergoing Anti-viral Therapy
- ClinicalTrials.gov ID
- NCT02508298
- Acronym / sponsor ID
- GGT0037
- Conditions
- Portal Hypertension, Cirrhosis
- Keywords
- ICG, ARFI, portal hypertension, cirrhosis, diagnostic study
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 41 participants (actual)
- Lead sponsor
- VA Connecticut Healthcare SystemUS federal agency
- Study start
- Apr 2014
- Primary completion
- Jul 2018 (actual)
- Study completion
- Jul 2019 (actual)
- First posted
- 24 Jul 2015 (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.
This is a prospective longitudinal study that will evaluate if changes (pre and post therapy) in indocyanine green (ICG) retention test and liver stiff ness (LS) and spleen stiffness (SS) as measured by acoustic radiofrequency impulse (ARFI) correlate with changes in portal pressure as determined by the hepatic vein pressure gradient (HVPG) in patients with compensated hepatitis C virus (HCV) cirrhosis undergoing antiviral therapy.
Detailed description
Subjects will be recruited from the outpatient setting of the West Haven VA Medical Center and the Yale Liver Clinic. Subjects between 18-85 years of age with compensated cirrhosis due to chronic hepatitis C virus (HCV) infection who will be starting anti-viral therapy to treat HCV within the next 3 months will be eligible for this study. 33 subjects (assuming 10% loss to follow-up) will be recruited and their participation will last from 6-12 months. The expected duration of the study is 2 years.
The primary end point of the study is to correlate the change (from baseline to after completing anti-HCV therapy) in ICG retention test, LS and SS as measured by ARFI with HVPG. After consent has been obtained, subjects will undergo ICG retention test, ARFI imaging and HVPG measurements before and after HCV therapy. Blood samples, demographic and clinical data will be collected before and after HCV therapy. Correlations between changes in HVPG and changes in ICG, LS and SS will be assessed. With 30 patients , we will have 80% power to perform a hypothesis test of the Pearson correlation assuming an observed correlation of 0.70 and a two-sided type I error rate of 0.05.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Indocyanine green retention test | Active comparator | Procedure: HVPG, Drug: Indocyanine Green Retention testA baseline venous sample of 5 ml of venous will be drawn for pre-infusion measurement. Under sterile conditions 0.5 mg/kg body weight of ICG will be injected into vein. Further blood samples (5 ml each) will be collected at 5, 10, 15 and 20 minute intervals after the injection from a peripheral vein in the opposite arm using another intravenous catheter. After serum is separated by centrifugation, optical densities will be measured at 804 nm using a calibrated method for measurement of ICG level s. ICG retention at 15 minutes and elimination rate constant will be calculated by fitting the serum disappearance curve to a single exponential decay equation.This will be compared to portal pressure measured by Hepatic Venous Portal Gradient (HVPG). |
| Liver stiffness measurement | Active comparator | Procedure: HVPG, Device: Liver stiffness measurementARFI measurements of the liver will be obtained using a standard ultrasound probe. The patient will be lying on his back and will be asked to hold his/her breath for 2-5 seconds during measurements.These will be compared to portal pressure measured by Hepatic Venous Portal Gradient (HVPG). |
| Spleen stiffness measurement | Active comparator | Procedure: HVPG, Device: Spleen stiffness measurementARFI measurements of the spleen will be obtained using a standard ultrasound probe. The patient will be lying on his back and will be asked to hold his/her breath for 2-5 seconds during measurements.These will be compared to portal pressure measured by Hepatic Venous Portal Gradient (HVPG). |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Age 18-85
- HCV infection (HCV-RNA positive)
- Compensated cirrhosis will be defined histologically and/or clinically (presence of compatible lab findings (platelet count ≤ 150,000, total bilirubin ≥ 2, serum albumin ≤ 3.5, INR ≥ 1.2) PLUS compatible physical exam features (cutaneous stigmata, gynecomastia in men, or splenomegaly) OR compatible radiological findings (nodular liver surface, splenomegaly, and/or collaterals). (The ultimate confirmation of the diagnosis of cirrhosis will be a baseline HVPG > 5 mmHg)
- Planned anti-HCV therapy in the next 3 months
Key exclusion criteria (6 listed)
- Any clinically-evident complication of cirrhosis that defines decompensation : jaundice, ascites, variceal hemorrhage, overt hepatic encephalopathy)
- Hepatocellular carcinoma
- Co-infection with HBV or HIV
- Ongoing alcohol abuse
- Occlusive portal thrombosis,
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 |
|---|---|---|
| HVPGAlso: Hepatic Venous Portal GradientHVPG will be performed by placing a placing a 7F venous catheter into a supra-hepatic vein and then advancing a 5F balloon-tipped catheter into the right hepatic vein. Wedged hepatic venous pressure (WHVP) and free hepatic venous pressure (FHVP) will be measured by connection to an external transducer and polygraph (PowerLab, ADInstruments Inc., Colorado Springs, CO). After inflating the balloon catheter, adequacy of the occlusion will be established by injection of a small amount of radiologic contrast medium. Hepatic Venous Pressure gradient (HVPG) will be calculated as the difference between WHVP and FHVP. | Procedure or surgery | Indocyanine green retention test, Liver stiffness measurement, Spleen stiffness measurement |
| Indocyanine Green Retention testAlso: ICG testAs decribed in arm descriptions | Drug | Indocyanine green retention test |
| Liver stiffness measurementAlso: LSAs decribed in arm descriptions; perfromed by ARFI | Device | Liver stiffness measurement |
| Spleen stiffness measurementAlso: SSAs decribed in arm descriptions; performed by ARFI | Device | Spleen stiffness measurement |
Primary outcome
Indocyanine Green before and after treatment of hepatitis c
Time frame: 2 years
Indocyanine Green will be obtained , this will be conducted before and after treatment for hepatitis c and is measured in mg/dl
3 secondary outcomes
Spleen stiffness before and after treatment of hepatitis c
Time frame: 2 years
Liver stiffness before and after treatment of hepatitis c
Time frame: 2 years
Hepatic venous pressure gradient before and after treatment of hepatitis c
Time frame: 2 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Nov 2019.
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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.
Guadalupe Garcia-Tsao, MD principal investigator
VA Connecticut Healthcare System
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing HVPG, Indocyanine Green Retention test and Liver stiffness measurement in people with Portal Hypertension and Cirrhosis, run by VA Connecticut Healthcare System at 2 sites in United States.
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 4 inclusion and 6 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: finished, as of the sponsor's last update on 25 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Indocyanine Green before and after treatment of hepatitis c (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 25 Nov 2019.