Comparative Study of Carvedilol Monotherapy Versus Combination Therapy With Endoscopic Variceal Ligation (EVL) for Primary Prophylaxis of Variceal Bleeding in Patients With Hepatocellular Carcinoma With High-Risk Esophageal Varices

February 15, 2025 updated by: Institute of Liver and Biliary Sciences, India

Comparative Study of Carvedilol Monotherapy Versus Combination Therapy With Endoscopic Variceal Ligation (EVL) for Primary Prophylaxis of Variceal Bleeding in Patients With Hepatocellular Carcinoma With High-Risk Esophageal Varices: A Randomized Trial

Esophageal varices are common in patients with hepatocellular carcinoma (HCC), with an incidence rate of 63% at the time of HCC diagnosis. Following an acute variceal bleed, the 6-week mortality rate for HCC patients is as high as 26%. Mortality rates escalate notably in HCC patients experiencing acute variceal bleeding, especially with increasing cancer severity indicated by BLCL status. Research suggests that the cumulative incidence rate of variceal bleeding at one year in patients receiving primary prophylaxis is almost half that of patients not receiving any prophylaxis.

Beta blockers are the standard therapy for primary prophylaxis in patients with portal hypertension to prevent variceal bleeding. Endoscopic band ligation has also shown promising results in recent studies. However, the combined impact of beta blockers and esophageal band ligation on lowering the incidence of variceal bleeding remains unstudied.

The aim of this study is to compare the efficacy of carvedilol monotherapy versus combination therapy with carvedilol and endoscopic band ligation in patients with HCC for primary prophylaxis of high-risk esophageal varices.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

Study population: All patients aged ≥ 18 years and ≤ 80 years admitted in Institute of Liver and Biliary Sciences, New Delhi with HCC of any cause and high risk esophageal varices and are giving written consent for participation in the study.

Study design - Single center, Open label, Randomized controlled trial Study period - 6 months Intervention - The patients will be randomized into Group -A (NSBB arm) and Group-B (EVL + NSBB arm). Both the group will receive the remaining treatment as per protocol Group A: Non-selective beta blocker (Carvedilol 3.125 mg BD for 3 days followed by 6.25 mg BD , maximum dose would be 12.5 mg BD , same shall be switch to maximum tolerable dose if SBP< 90 , H,R<55) Group B: Non-selective beta blocker (Carvedilol 3.125 mg BD for 3 days followed by 6.25 mg BD , maximum dose would be 12.5 mg BD , same shall be switch to maximum tolerable dose if SBP< 90 , H,R<55) + EVL every 3 weeks till eradication of varices followed by every 3 months.

Monitoring and assessment: Monitoring and evaluation would be done once a month for first 3 months then at 6th month.

Study Type

Interventional

Enrollment (Estimated)

100

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • India
    • Delhi
      • New Delhi, Delhi, India, 110070
        • Institute of Liver & Biliary Sciences (ILBS)
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Age 18-80 years
  2. Cirrhosis with HCC
  3. High risk oesophageal varices (*large or small with RCS)
  4. Valid consent

Exclusion Criteria:

  1. Any contra-indication to beta-blockers
  2. Any EVL or Sclerotherapy within last 3 months
  3. Any past history of TIPS or surgery for portal hypertension
  4. HCC with BCLC-D
  5. Patients with past history of variceal bleed.
  6. Patient With Liver transplant expected in next 2 weeks would be excluded

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: NSBB+EVL
Non-selective beta blocker (Carvedilol 3.125 mg BD for 3 days followed by 6.25 mg BD , maximum dose would be 12.5 mg BD , same shall be switch to maximum tolerable dose if Systolic BP< 90 , H,R<55) + EVL every 3 weeks till eradication of varices followed by every 3 months
Drug: Carvedilol Tablets
Non-selective beta blocker (Carvedilol 3.125 mg BD for 3 days followed by 6.25 mg BD , maximum dose would be 12.5 mg BD , same shall be switch to maximum tolerable dose if Systolic BP< 90 , H,R<55)
Procedure: Endoscopic Variceal Ligation
EVL every 3 weeks till eradication of varices followed by every 3 months.
Active Comparator: NSBB
Non-selective beta blocker (Carvedilol 3.125 mg BD for 3 days followed by 6.25 mg BD , maximum dose would be 12.5 mg BD , same shall be switch to maximum tolerable dose if Systolic BP< 90 , H,R<55)
Drug: Carvedilol Tablets
Non-selective beta blocker (Carvedilol 3.125 mg BD for 3 days followed by 6.25 mg BD , maximum dose would be 12.5 mg BD , same shall be switch to maximum tolerable dose if Systolic BP< 90 , H,R<55)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Proportion of patients of cirrhosis with HCC and high risk oesophageal varices on carvedilol developing variceal bleed with or without EVL in 6months follow up.
Time Frame: 6 months
6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of patient developing variceal bleed while on therapy with Tyrosine Kinase Inhibitors despite on carvedilol with or without EVL
Time Frame: 6 months
6 months
Proportion of patient developing variceal bleed while on therapy with immunotherapy despite on carvedilol with or without EVL.
Time Frame: 6 months
6 months
Percentage of patient of cirrhosis with HCC and Portal Vein Tumoral Thrombosis developing variceal bleed while on carvedilol with or without EVL.
Time Frame: 6 months
6 months
Proportion of patients having post-EVL ulcer bleed after endoscopic variceal ligation.
Time Frame: 6 months
6 months
Proportion of patients with change in non invasive test for portal hypertension in both groups.
Time Frame: 6 months
Non invasive markers: LSM, SSM, APRI Score, ALBI Score
6 months
Proportion of patient developing variceal bleed after SBRT for advanced Hepatocellular carcinoma
Time Frame: 6 months
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Institute of Liver and Biliary Sciences, India

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

February 20, 2025

Primary Completion (Estimated)

January 31, 2026

Study Completion (Estimated)

January 31, 2026

Study Registration Dates

First Submitted

January 27, 2025

First Submitted That Met QC Criteria

February 15, 2025

First Posted (Actual)

March 25, 2025

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

February 15, 2025

Last Verified

January 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ILBS-HCC-08

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Hepatocellular Carcinoma

Clinical Trials on Carvedilol Tablets

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Argentina

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe