Direct Portal Pressure Measurement Via Endoscopic Ultrasound in Advanced Chronic Liver Disease (EVADIPP) (EVADIPP)

Evaluation of Direct Portal Pressure Measurement by Endoscopic Ultrasound in Advanced Chronic Liver Disease and Newly Diagnosed Clinically Significant Portal Hypertension (EVADIPP)

A minimally invasive procedure to directly assess portal pressure gradient under endoscopic ultrasound guidance (EUS-PPG) has become available and initial data have proved the technique to be safe. Aims of our proposal are: (i) to assess performance of EUS-PPG as compared to HVPG in evaluating hemodynamic response to non selective betablockers (NSBBs) in a large cohort of patients with CSPH;(ii) identification of markers of hemodynamic response(iii) identification of factors potentially affecting the accuracy of PPG measurement.

Study Overview

• Status: Recruiting
• Conditions: Portal Hypertension
• Intervention / Treatment: Device: EUS PPG measurement

Detailed Description

Specific Aim 1 To explore the correlation between endoscopic ultrasound (EUS)-guided portal pressure gradient (PPG) and hepatic venous pressure gradient (HVPG) in evaluation of hemodynamic response to non-selective beta blockers (NSBBs) in patients with advanced chronic liver disease and high risk varices. The investigators will perform EUS-PPG measurement and HVPG measurement at baseline and after NSBBs titration in enrolled patients. Hemodynamic response to medical therapy is defined as either a decrease in HVPG by >20% of the baseline value or an absolute value of HVPG < 12 mmHg after dose titration.

Correlation between PPG/HVPG values and development of portal hypertension-related gastrointestinal bleeding or liver- related events (ascites, spontaneous bacterial peritonitis, and hepatic encephalopathy) will be clinically assessed during follow-up with outpatients visits every 2-3 months.

Specific Aim 2 Identification of other markers of hemodynamic response to non selective beta blockers (NSBBs), with focus on elastography modifications and gut microbiota composition. To identify predictors of hemodynamic response, splenic and hepatic elastography measurement will performed at baseline and after NSBBs titration. In the same way the investigators will evaluate the gut microbiota before and after the start of therapy with NSBBs.

Specific Aim 3 Identification of factors potentially affecting the accuracy of PPG measurement. It is well-known that deep sedation may cause inaccurate HVPG values, while mild sedation with low dose midazolam does not modify the HVPG. In a subgroup of enrolled patients the investigators will perform PPG measurement with deep and mild sedation in order to investigate influence of deep sedation on PPG measurement accuracy.

• Study Type: Observational
• Enrollment (Estimated): 50

Contacts and Locations

• Study Contact: Name: Francesco Santopaolo, MD; Phone Number: +393492754288; Email: francesco.santopaolo@policlinicogemelli.it
• Study Contact Backup: Name: Elisabetta Creta, SC; Email: elisabetta.creta@policlinicogemelli.it

Study Locations

• Italy
  • Roma, Italy, 00168
    • Recruiting
    • Policlinico Gemelli IRCCS
    • Contact: Francesco Santopaolo, MD; Phone Number: +393492754288; Email: francesco.santopaolo@policlinicogemelli.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Consecutive outpatients with newly diagnosed esophago-gastric varices or with high suspicion of CSPH at non-invasive tests, naïve to treatment with NSBBs, will be evaluated over a two-years period.

Description

Inclusion Criteria:

• Patients with newly diagnosed esophago-gastric varices or with high suspicion of CSPH at non-invasive tests (porto- systemic collaterals at imaging, platelet count <150.000 x mm3, spleen size >13 cm in the largest axis, alteration of elastography parameters of the liver or spleen)
• naïve to treatment with NSBBs,

Exclusion Criteria:

• Child Pugh >A6
• Hepatocellular carcinoma
• Portal vein thrombosis

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measurement of the portal pressure gradient though endoscopic ultrasound (EUS) and hepatic venous pressure gradient (HVPG) to evaluate the hemodynamic response to non-selective beta blockers (NSBBs)	The investigators will measure portal pressure gradient through EUS-PPG measurement at baseline and after NSBBs titration in enrolled patients.	24 months
HVPG Measurement Before and After NSBB Titration in Portal Hypertension	The investigators will measure portal pressure gradient through HVPG measurement at baseline and after NSBBs titration in enrolled patients.	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Markers of hemodynamic response	Spleen Stiffness Measurement (SSM) will be assessed by transient elastography before starting NSBB and using a FibroScan® (Echosens, Paris, France) after an overnight fasting.	24 months
Identifying Markers of Hemodynamic Response in Portal Hypertension	Liver Stiffness Measurement (LSM) will be assessed by transient elastography before starting NSBB and using a FibroScan® (Echosens, Paris, France) after an overnight fasting.	24 months
Clinical and Biochemical Indicators of Hemodynamic Response	The gut microbiota will be collected before and after the start of therapy with NSBBs. Fecal samples will be collected at home in a commercial sterile, dry screw-top container, and frozen at -80 °C within 24 hours, until further processing. Baseline and post NSBBs treatment blood samples collected from portal vein will be drawn, processed and stored at -80°C within 1 hour, until further processing.	24 months

Collaborators and Investigators

• Sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
• Investigators: Principal Investigator: Francesco Santopaolo, MD, Fondazione Policlinico A. Gemelli IRCCS, Rome

Study record dates

Study Major Dates

• Study Start (Actual): September 11, 2023
• Primary Completion (Estimated): April 1, 2025
• Study Completion (Estimated): April 1, 2026

Study Registration Dates

• First Submitted: September 11, 2023
• First Submitted That Met QC Criteria: February 15, 2024
• First Posted (Actual): February 20, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 11, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Digestive System Diseases; Hypertension; Liver Diseases; Hypertension, Portal
• Other Study ID Numbers: 5486

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No