Patients With Compensated Liver Cirrhosis
Conditions
Keywords
MBT, CSPH, HVPG
Brief summary
This study will be used to train an algorithm using Methacetin breath test (MBT) measures and to select a cut-off to determine presence or absence of Clinically Significant Portal Hypertension (CSPH) as defined by Hepatic Venous Gradient Pressure (HVPG) ≥ 10mmHg,
Detailed description
The portal pressure leaving the liver is measured by using a balloon catheter before and after a wedge. The difference of the pressure between the wedge and the free is the hepatic venous pressure gradient. Methacetin breath test is hypothesized to also identify CSPH and the agreement to the reference standard (HVPG) will be assessed in this study.
Interventions
DEVICEMethacetin Breath Test
13C labelled methacetin solution for breath test monitoring
Sponsors
Meridian Bioscience, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult men or women (\>18 years of age) * Known chronic liver disease with cirrhosis * Europe: Indicated to undergo HVPG testing * US: Consented for HVPG * For patients treated with beta blockers: They have to be on a stable dose for at least 6 weeks prior to any study related tasks * For patients who stopped their treatment with beta blockers: Their last dose should be at least 6 weeks prior to any study related tasks
Exclusion criteria
* Decompensated cirrhosis as clinically defined by the presence of ascites, hepatic encephalopathy, variceal bleeding or hepatorenal syndrome * Renal failure (creatinine \> 2.5 mg/dl) * Known acute renal tubular disease Known hypotension (Systolic Pressure \<100mmHg) * Hypocoagulablity defined as PT \>6 and INR \>2.3. * Congestive heart failure (assessed clinically as NIHA \>2) * Known pulmonary hypertension (right ventricular systolic pressure \> 45 mm Hg) * Uncontrolled diabetes mellitus (HBA1C \>9.5gr%) * Concurrent prednisone or immunosuppressive treatment, if therapy and/or response to treatment are not stable for at least 3 months. * Documented or suspected hepatocellular carcinoma * Gastric bypass surgery or extensive small bowel resection * Total parenteral nutrition * Any organ transplant recipient * Pregnant or breast feeding * Allergy to acetaminophen and/or other related medications * Documented drug-related concurrent hepatotoxicity or drug-related silent steatosis or drug-related fibrosis (e.g. amiodarone, methotrexate and tamoxifen) * Uncontrolled malabsorption or diarrhea * Documented non-cirrhotic PHT, partial / complete portal venous occlusion, hepatic venous occlusion, previous PHT surgery, or placement of a transjugular intrahepatic portosystemic shunt (TIPS) * Primary or secondary biliary cirrhosis, primary or secondary sclerosing cholangitis, hepatic sarcoidosis, or other cholestatic disorders * Subjects unable to perform the MBT within 7 days of HVPG procedure. * Subject should not have taken any of the following for at least 48 hours prior to the breath test: Acyclovir , allopurinol, amiodarone, carbamazepine, cimetidine, ciprofloxacin, daidzein, (herbal) disulfiram, echinacea, enoxacin, famotidine, fluvoxamine, methoxsalen, mexiletine, montelukast, norfloxacin, phenylpropanolamine, phenytoin, propafenone, rifampin, terbinafine, ticlopidine, thiabendazole, verapamil, zileuton or oral contraceptives or any medication that might interfere with Methacetin metabolism or might affect CYP 1A2 * Subject should not have taken amiodarone or statins within the last 30 days prior to the breath test or HVPG procedure
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| CSPH (Clinically Significant Portal Hypertension) | 1 hour | Clinically significant portal hypertension is defined as Hepatic Venous Pressure Gradient (HVPG)\>=10mmHg, whereby the portal pressure leaving the liver is measured by using a balloon catheter before and after a wedge. The difference of the pressure between the wedge and the free is the hepatic venous pressure gradient. Methacetin breath test is hypothesized to also identify CSPH and the agreement to the reference standard (HVPG) will be assessed in this study. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Hepatic Venous Pressure Gradient (HVPG)>=12; Severe Portal Hypertension (SPH) | 1 hour | Hepatic Venous Pressure Gradient greater than 12 (SPH) is an indicator of bleeding varices. whereby the portal pressure leaving the liver is measured by using a balloon catheter before and after a wedge. The difference of the pressure between the wedge and the free is the hepatic venous pressure gradient. Methacetin breath test is hypothesized to also identify SPH and the agreement to the reference standard (HVPG) will be assessed in this study. |
Countries
France, Spain, Switzerland, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Compensated Cirrhotic Patients A methacetin breath test will be performed on patients who are undergoing the HVPG procedure due to their clinical indication of compensated cirrhosis.
Methacetin Breath Test: 13C labelled methacetin solution for breath test monitoring | 246 |
| Total | 246 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Device malfunction | 1 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Compensated Cirrhotic Patients |
|---|---|
| Age, Continuous | 60.6 years STANDARD_DEVIATION 9.27 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 242 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Region of Enrollment France | 40 participants |
| Region of Enrollment Spain | 158 participants |
| Region of Enrollment Switzerland | 9 participants |
| Region of Enrollment United States | 39 participants |
| Sex: Female, Male Female | 93 Participants |
| Sex: Female, Male Male | 153 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 246 |
| other Total, other adverse events | 2 / 246 |
| serious Total, serious adverse events | 1 / 246 |
Outcome results
Primary
CSPH (Clinically Significant Portal Hypertension)
Clinically significant portal hypertension is defined as Hepatic Venous Pressure Gradient (HVPG)\>=10mmHg, whereby the portal pressure leaving the liver is measured by using a balloon catheter before and after a wedge. The difference of the pressure between the wedge and the free is the hepatic venous pressure gradient. Methacetin breath test is hypothesized to also identify CSPH and the agreement to the reference standard (HVPG) will be assessed in this study.
Time frame: 1 hour
Population: Compensated cirrhotic patients with CSPH based on breath test compared to CSPH from HVPG (reference standard)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Compensated Cirrhotic Patients With CSPH | CSPH (Clinically Significant Portal Hypertension) | 81.82 percentage of agreement |
Secondary
Hepatic Venous Pressure Gradient (HVPG)>=12; Severe Portal Hypertension (SPH)
Hepatic Venous Pressure Gradient greater than 12 (SPH) is an indicator of bleeding varices. whereby the portal pressure leaving the liver is measured by using a balloon catheter before and after a wedge. The difference of the pressure between the wedge and the free is the hepatic venous pressure gradient. Methacetin breath test is hypothesized to also identify SPH and the agreement to the reference standard (HVPG) will be assessed in this study.
Time frame: 1 hour
Population: Compensated cirrhotic Patients with Severe Portal Hypertension based on MBT compared to HVPG (reference standard)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Compensated Cirrhotic Patients With CSPH | Hepatic Venous Pressure Gradient (HVPG)>=12; Severe Portal Hypertension (SPH) | 76.39 percentage of agreement |