Portal Hypertension Related to Cirrhosis
Conditions
Keywords
portal hypertension, EUS-PPG, HVPG, cirrhosis, non-selective beta blockers
Brief summary
The goal of this clinical trial is to learn if endoscopic ultrasound (EUS)-guided portal pressure measurement can determine the treatment response to non-selective beta-blockers (NSBB) in patients with cirrhosis and clinically significant portal hypertension (CSPH). Participants will undergo EUS-guided portal pressure measurement before start of Carvedilol en after three months of treatment. EUS-guided measurements will be paired with transjugular hepatic venous pressure gradient (HVPG) measurement as well as non-invasive tests for assessment of portal hypertension.
Interventions
PROCEDUREendoscopic ultrasound-guided portal pressure measurement
The portal pressure gradient will be determined by endoscopic ultrasound-guided pressure measurement in the hepatic vein and the portal vein. The gradient will be calculated by substracting the hepatic vein pressure from the portal vein pressure.
Sponsors
Universitaire Ziekenhuizen KU Leuven
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Patients with a clinical and/or pathological diagnosis of compensated cirrhosis. * Patients with suspicion of CSPH and thus indication for NSBB treatment. * Patients not yet on NSBB therapy. * Patients willing and able to undergo repeated HVPG and EUS-guided pressure measurements as per protocol.
Exclusion criteria
General criteria * Patient is \<18 or \>80 years of age * Patient is pregnant, breast-feeding or planning to become pregnant during the course of the study * Patient is unwilling or unable to sign the informed consent * Patients in whom general anesthesia or endoscopic procedures are contraindicated Medical criteria * Patients with cirrhosis and HCC Portopulmonary hypertension Portal or splanchnic venous thrombosis Prior TIPS Prior liver transplantation * Non-cirrhotic portal hypertension or pre-sinusoidal liver disease * Cholestatic liver disease with total bilirubin \>3 mg/dl * Previous total or partial splenectomy * Known infection that is not controlled by medical intervention * Patients with contraindications for non-selective beta-blocker therapy, including but not limited to the following baseline vital signs: Systolic BP \<100 mmHg HR \<50 bpm * Patients with reduced life expectancy described by an ASA score of 4 or 5 * INR \>1.7 or platelet count \<50.000 per mm3 * eGFR \<50 ml/min/1.73m2 (CKD-EPI formula) Anatomical criteria * Anatomical abnormalities that prevent access via EUS-guided puncture to the hepatic vein or intrahepatic portion of the portal vein, including anatomy that predisposes to difficult to reach puncture sites or an inadequate needle angle. * Visualization of ascites interposing the puncture tract on EUS * Diagnosis of portal vein thrombosis during EUS * Evidence of active gastrointestinal bleeding during EUS
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| EUS-guided response assessment to NSBB in the treatment of CSPH. | Three months | To assess if a positive response to non-selective beta-blockers (NSBB) treatment, as determined by a reduction of 10% or more in the hepatic venous pressure gradient (HVPG) and/or a decrease to values less than 12 mmHg, can be similarly observed using endoscopic ultrasound-guided portal pressure gradient (EUS-PPG) measurement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Correlation of EUS-PPG with HVPG | Three months | To assess the correlation of EUS-PPG and HVPG before treatment start as well as after treatment start with NSBB |
| Correlation of FHVP with HVP. | Three months | To assess the correlation of EUS-guided hepatic venous pressure (HVP) and transjugular free hepatic venous pressure (FHVP) measurement before treatment start as well as after treatment start with NSBB. |
| Correlation of PVP with WHVP. | Three months | To assess the correlation of EUS-guided portal venous pressure (PVP) and transjugular wedged hepatic venous pressure (WHVP) measurement before treatment start as well as after treatment start with NSBB. |
| CSPH assessed via EUS-guided pressure measurement. | Three months | To determine if the current definition of CSPH (i.e. HVPG \>/= 10 mmHg) can be adopted for portal tension measurement via EUS-PPG. |
| Correlation of sequential EUS-PPG and HVPG with non-invasive assessment tools before/after treatment with NSBB. | Three months | To evaluate the correlation of sequential PPG and HVPG measurements, before and after treatment start with NSBB, with (the evolution of) non-invasive assessment tools. Non-invasive tools evaluated are fibrosis-4 (FIB-4) score, AST to platelet ratio index (APRI), liver stiffness-spleen size-to-platelet ratio-score (LSPS), platelet count to spleen diameter ratio (PSR), liver stiffness measurement (LSM) and spleen stiffness measurement (SSM). |
| Safety of repeated EUS-PPG | 14 weeks | To assess the number of participants with any adverse event related to the (repeated) EUS-guided portal pressure gradient measurements. Potential risks associated with the study-specific intervention include fever, (minor) haemorrhage, (minor) infection, inflammation, pain/discomfort, (minor) vessel trauma, vessel occlusion/thrombosis, allergic reaction to medication\*, aspiration\*, cardiac arrhythmia or arrest\*, respiratory depression or arrest\*, death\*. Adverse events indicated with \* are related to the gastrointestinal endoscopic procedure required for the EUS-PPG intervention and are not specific to the device. |
Countries
Belgium
Contacts
CONTACTEmma Vanderschueren, MD
CONTACTPetra Windmolders
PRINCIPAL_INVESTIGATORSchalk van der Merwe, MD, PhD
Universitaire Ziekenhuizen KU Leuven
Outcome results
None listed