The Use of Endoscopic Ultrasound-Guided Portal Pressure Measurements to Guide Beta-Blocker Therapy in Patients With Compensated Cirrhosis

This pilot study to determine the feasibility of EUS-Portal Pressure Measurements to guide Beta-Blocker Therapy in patients with compensated cirrhosis .The study will be a prospective tandem controlled trial consisting of 30 patients who are already undergoing routine endoscopy screening for portal hypertension as part of their routine clinical care . The decision to start a beta-blocker will be made at the conclusion of the EGD based on the endoscopic findings (presence of esophageal varices). EUS-PPG will then be performed and measurements will be collected. The primary outcome is the feasibility of guiding B blocker therapy by EGD+EUS-PPG at the time of EGD for variceal screening. The secondary outcome will be the proportion of patients initiated on beta-blocker therapy based on EGD alone versus EGD+EUS-PPG

Study Overview

• Status: Not yet recruiting
• Conditions: Cirrhosis; Portal Hypertension; Compensated Cirrhosis
• Intervention / Treatment: Diagnostic test: EUS

Detailed Description

The study will be a prospective tandem controlled trial consisting of 30 patients who are undergoing EGD followed by EUS-PPG at Los Angeles County + University of Southern California Medical Center (LAC+USC).

Only patients undergoing endoscopic screening for portal hypertension as part of routine clinical care will be considered for the study.

All procedures will be performed with the patient under moderate sedation or monitored anesthesia care as is standard in our endoscopy unit. EGD with a forward-viewing scope will be performed initially in all patients to evaluate and document the presence of esophageal varices. Any other endoscopic evidence of portal hypertension, such as portal hypertensive gastropathy or gastric varices, will also be documented.

The decision to start a beta-blocker will be made at the conclusion of the EGD based on the endoscopic findings (presence of any esophageal varices).

EUS-PPG will then be performed. Using the dedicated 25-gauge portal systemic pressure measurement needle, the hepatic venous system and portal venous system will be directly accessed to allow measurements. The mean portal pressure gradient will be recorded. We will then record whether beta-blockers would be initiated based on portal pressure measurements ≥10mmHg.

The peri-procedure management will be performed according to standard of care within our endoscopy unit. As is our standard clinical care for patients with portal hypertension, for patients found to have evidence of portal hypertension we will start the beta-blocker carvedilol 6.25mg twice a day will be started on the day following the procedure. If tolerated, the dose will be increased to 12.5mg twice a day after one month.

The patients will be blinded to whether or not the decision to start beta-blockers was based on EGD, EUS-PPG or both findings. The patient will be followed clinically by the principal investigator assisted by a full time study coordinator and team with extensive prospective clinical trials experience

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Alex Rodriguez, BS; Phone Number: 323-409-6939; Email: Alex.Rodriguez@med.usc.edu
• Study Contact Backup: Name: Jessica D Serna, BS; Phone Number: 323-409-6939; Email: Jessica.Serna@med.usc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 18-75 years of age.
2. diagnosis of Child-Pugh class A cirrhosis who present to LAC+USC for variceal screening.

A diagnosis of cirrhosis will be determined histologically based on biopsy alone or clinically by reviewing notes from a gastroenterology or hepatology provider with imaging and clinical history consistent with cirrhosis.

Exclusion Criteria:

1. Prior decompensation, which includes a history of variceal hemorrhage, ascites, and/or hepatic encephalopathy;
2. other complications of cirrhosis that can affect portal pressures, such as splenic or portal vein thrombosis and/or hepatocellular carcinoma,
3. use of any medications (i.e. current beta-blocker use) or prior procedure that affects splanchnic hemodynamics or portal pressure;
4. contraindications to beta-blockers, including resting heart rate <60, systolic blood pressure <90, history of bronchospasm;
5. current incarceration;
6. pregnancy; and
7. inability to give informed consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Beta Blocker at EUS	Diagnostic test: EUS; The decision to start a beta-blocker will be made at the conclusion of the EGD based on the endoscopic findings (presence of esophageal varices)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility of guiding B blocker therapy for variceal screening	Feasibility will be measured by procedure success, Intra-procedure times, and adverse events.	Procedure through study completion, an average of 7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Initiation on beta-blocker therapy based EGD alone versus EGD+EUS-PPG.	The secondary outcome will be the proportion of patients initiated on beta-blocker therapy based on EGD alone versus EGD+EUS-PPG.	Baseline

Collaborators and Investigators

• Sponsor: University of Southern California
• Investigators: Principal Investigator: James Buxbaum, MD, LAC+USC Medical Center

Study record dates

Study Major Dates

• Study Start (Anticipated): December 1, 2023
• Primary Completion (Anticipated): May 1, 2025
• Study Completion (Anticipated): July 1, 2025

Study Registration Dates

• First Submitted: April 17, 2022
• First Submitted That Met QC Criteria: April 26, 2022
• First Posted (Actual): May 3, 2022

Study Record Updates

• Last Update Posted (Estimate): March 6, 2023
• Last Update Submitted That Met QC Criteria: March 2, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Liver Diseases; Fibrosis; Liver Cirrhosis; Hypertension, Portal
• Other Study ID Numbers: APP-22-01828

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