Carvedilol Plus EVL or Not for the Primary Prevention of Esophageal Variceal Bleeding in Carvedilol Non-responders (CVL-NR)

February 10, 2025 updated by: Taipei Veterans General Hospital, Taiwan

Carvedilol Plus Endoscopic Ligation or Not for the Primary Prevention of Esophageal Variceal Bleeding in Carvedilol Non-responders: a Randomized Controlled Trial

The goal of this clinical trial is to evaluate whether carvedilol plus endoscopic variceal ligation (EVL) is more effective for the primary prevention of esophageal variceal bleeding than carvedilol alone in carvedilol non-responders. It will also learn about the safety of carvedilol combined with EVL in patients with cirrhosis.

The main questions it aims to answer are:

Whether carvedilol plus EVL is more effective than carvedilol alone in preventing the first esophageal variceal bleeding in cirrhotic patients unresponsive to carvedilol.

What medical problems do participants have when taking carvedilol or taking carvedilol combined with undergoing EVL? Researchers will compare the efficacy and safety of carvedilol with or without EVL in preventing the first esophageal variceal bleeding in cirrhotic patients unresponsive to carvedilol.

Participants will:

Take carvedilol every day (start from 6.25 mg/d and then titrate to 12.5 mg/d if tolerable) and undergo EVL every 3-4 weeks until variceal eradication followed by regular endoscopic follow-up according to the protocol, or Take carvedilol alone every day (start from 6.25 mg/d and then titrate to 12.5 mg/d if tolerable).

Visit the clinic once every 2-3 months for checkups and tests. Keep a diary of their vital signs (SBP, DBP, and HR) as well as symptoms.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Gastro-esophageal variceal bleeding is a major complication of portal hypertension and carries a high rate of rebleeding and mortality. How to prevent the first esophageal variceal bleeding (EVB) in patients with cirrhosis and portal hypertension has always been a very important issue. According to the latest Baveno VII consensus on the treatment of portal hypertension published in December 2021, nonselective beta-blockers (NSBB) should be used first to prevent decompensation in patients with clinically significant portal hypertension. Endoscopic variceal ligation (EVL) is recommended for compensated patients with high-risk esophageal varices (EVs) who have contraindications or an intolerance to NSBBs.

Carvedilol is a kind of NSBB and has extra intrinsic anti-α1 adrenergic activity. Carvedilol can reduce hepatic venous pressure gradient (HVPG) better than propranolol, and is currently the drug of choice for the primary prevention of EVB in patients with cirrhosis and CSPH. Although the HVPG-lowering effect of carvedilol is stronger than that of propranolol, up to 38-46% patients with CSPH are still carvedilol non-responders. Follow-up upper gastrointestinal endoscopy of these patients may show EVs become larger, more numerous, or have new red color signs, which indicate the increasing risk of EVB. However, studies discussing treatment options for patients with cirrhosis and EVs who do not respond to carvedilol therapy are scarce.

In this project, the investigators will initiate an open-label randomized controlled trial aiming at comparing the efficacy of carvedilol plus EVL or not for the primary prevention of EVB in cirrhotic patients who are carvedilol non-responders. The investigators will also explore if there is any difference between the two groups in terms of other upper gastrointestinal bleeding, non-bleeding liver decompensation (such as new onset/worsening ascites, hepatic encephalopathy, spontaneous bacterial peritonitis, and hepatorenal syndrome), overall survival, adverse events, tolerability and safety. The investigators will also analyze whether there is a difference of the two groups in preventing the first EVB in patients with varying degrees of cirrhosis who are carvedilol non-responders.

Study Type

Interventional

Enrollment (Estimated)

80

Phase

  • Phase 4

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

  • Taiwan
      • Taipei, Taiwan, 11217
        • Recruiting
        • Taipei Veterans General Hospital
        • Contact:
        • Contact:
        • Principal Investigator:
          • Tsung-Chieh Yang, MD

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:

- Cirrhotic patients with esophageal varices who, after carvedilol treatment, continue to experience variceal enlargement or develop new red color signs.

Exclusion Criteria:

  • Age under 18 or over 90 years.
  • History of esophageal variceal bleeding.
  • Previous treatment for esophageal varices, including endoscopic variceal ligation, endoscopic sclerotherapy, transjugular intrahepatic portosystemic shunt, or surgery.
  • Contraindications to non-selective beta-blockers, including severe atrioventricular block, chronic obstructive pulmonary disease (COPD), asthma, uncontrolled diabetes mellitus, or severe peripheral artery disease.
  • Presence of end-stage organ diseases, including hepatocellular carcinoma or other terminal cancers, heart failure, or renal failure.
  • Pregnant women.
  • Refusal to participate in the study.

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
Active Comparator: Carvedilol plus endoscopic variceal ligation
Take carvedilol every day (start from 6.25 mg/d and then titrate to 12.5 mg/d if tolerable) and undergo EVL every 3-4 weeks until variceal eradication followed by regular endoscopic follow-up according to the protocol.
Other: Carvedilol plus endoscopic variceal ligation
Take carvedilol every day (start from 6.25 mg/d and then titrate to 12.5 mg/d if tolerable) and undergo EVL every 3-4 weeks until variceal eradication followed by regular endoscopic follow-up according to the protocol.
Placebo Comparator: Carvedilol alone
Take carvedilol alone every day (start from 6.25 mg/d and then titrate to 12.5 mg/d if tolerable).
Drug: Carvedilol alone
Take carvedilol alone every day (start from 6.25 mg/d and then titrate to 12.5 mg/d if tolerable).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Esophageal variceal bleeding
Time Frame: 3 years
The cumulative incidence of esophageal variceal bleeding
3 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival
Time Frame: 3 years
3 years
Adverse events
Time Frame: 3 years
3 years
Other upper gastrointestinal bleeding
Time Frame: 3 years
The cumulative incidence of other upper gastrointestinal bleeding
3 years
First/further nonbleeding liver decompensation
Time Frame: 3 years
Events that defined first/further nonbleeding liver decompensation were based on the Baveno VII consensus.
3 years

Other Outcome Measures

Outcome Measure
Time Frame
Primary and secondary outcomes categorized by Child-Pugh class in the subgroup analysis
Time Frame: 3 years
3 years

Collaborators and Investigators

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

Sponsor

Taipei Veterans General Hospital, Taiwan

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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 (Actual)

January 6, 2025

Primary Completion (Estimated)

October 1, 2030

Study Completion (Estimated)

October 1, 2030

Study Registration Dates

First Submitted

September 10, 2024

First Submitted That Met QC Criteria

September 10, 2024

First Posted (Actual)

September 19, 2024

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

February 10, 2025

Last Verified

February 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2024-08-017A

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

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.

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