Endoscopic Band Ligation (EBL) Versus Propranolol for Primary Prophylaxis of Variceal Bleeding

Randomized Controlled Trial Comparing Propranolol, Endoscopic Banding Ligation, and Combined Treatment to Prevent First Variceal Hemorrhage in Patients With Liver Cirrhosis

This study is performed to compare the efficacy and safety of EBL, propranolol, and EBL combined with propranolol in patients with medium or large varices.

Study Overview

• Status: Unknown
• Conditions: Cirrhosis; Variceal Bleeding
• Intervention / Treatment: Procedure: Endoscopic band ligation; Drug: Propranolol; Procedure: EBL+Propranolol

Detailed Description

Current guidelines recommend prophylactic treatment with propranolol or endoscopic band ligation (EBL) to prevent variceal bleeding in patients with medium or large varices. However, it is unclear which treatment is more useful in regard to prevention of variceal bleeding as well as safety. In addition, the efficacy and safety of the combination of EBL and propranolol is not still defined. This study is performed to compare the efficacy and safety of EBL, propranolol, and EBL combined with propranolol in patients with medium or large varices.

• Study Type: Interventional
• Enrollment (Anticipated): 288
• Phase: Phase 4

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 136-705
    • Recruiting
    • Korea University Anam Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 66 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Liver cirrhosis
• Age between 18 and 70 years
• Esophageal varices with high bleeding risk: more than F2 and red color sign
• No previous history of upper gastrointestinal bleeding
• No previous history of endoscopic, radiologic, or surgical therapy for varices or ascites
• Do not take beta-blocker, ACE inhibitor, or nitrate
• Child-Pugh score <12

Exclusion Criteria:

• Patients with systolic blood pressure <100 mmHg or basal heart rate <60/min
• Portal vein thrombosis
• Uncontrolled ascites or hepatic encephalopathy
• Severe coagulation disorder: prothrombin time <40% (or INR >1.7) or platelet count <30,000/mm3
• Medium or large sized gastric or duodenal varices
• Coexisting malignancy
• Severe cardiovascular disorder, renal failure, peritonitis, sepsis
• Severe erosive esophagitis, severe esophageal stricture, active gastric or duodenal ulcer
• Contraindication to beta-blocker
• Pregnancy
• Refusal to give consent to participate in the trial

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Endoscopic band ligation; Endoscopic band ligation until eradication of esophageal varices with 4 weeks interval, and then follow-up endoscopy with 3-6 months interval until 36 months after enrollment	Procedure: Endoscopic band ligation; Perform EBL within 7 days after randomization; Apply 1-2 band/column/session to varices in the distal 5-7 cm of the esophagus till they are eradicated (disappearance or too small to apply band) with interval of 4 weeks (at 4,8,12 weeks after initial treatment); Acid suppression using proton pump inhibitor until eradicated.; After eradication, then follow-up endoscopy according to a preset schedule (at 1, 2, 3 months after initial treatment, then every 3-6 months until 36 months).; Other Names: EBL
Active Comparator: Propranolol; start with 20 mg b.i.d, and adjust by 20-40 mg/d reaching reduction by 25% in HR or HR ≤55/min. After reaching target HR, then follow-up according to a preset schedule (at 1, 2, 3 months after initial treatment, then every 3 months until 36 months)	Drug: Propranolol; start with 20 mg of propranolol b.i.d; Adjust by 20-40 mg/day reaching reduction by 25 percent in HR or HR less than 55/min; After reaching target HR, then FU according to a preset schedule (at 1, 2, 3 months after initial treatment, then every 3 months until 36 months); Other Names: Beta blocker
Active Comparator: EBL+Propranolol; EBL until eradication of esophageal varices with 4 weeks interval, and then follow-up endoscopy with 3-6 months interval until 36 months after enrollment; start with 20 mg of propranolol b.i.d, and adjust by 20-40 mg/d reaching reduction by 25% in HR or HR ≤55/min. After reaching target HR, then follow-up according to a preset schedule (at 1, 2, 3 months after initial treatment, then every 3 months until 36 months)	Procedure: EBL+Propranolol; EBLPerform EBL within 7 days after randomizationApply 1-2 band/column/session to varices in the distal 5-7 cm of the esophagus till they are eradicated (disappearance or too small to apply band) with interval of 4 weeks (at 4,8,12 weeks after initial treatment)Acid suppression using proton pump inhibitor until eradicated.After eradication, then follow-up endoscopy according to a preset schedule (at 1, 2, 3 months after initial treatment, then every 3-6 months until 36 months).; Propranololstart with 20 mg b.i.dAdjust by 20-40 mg/day reaching reduction by 25 percent in HR or HR less than 55/minAfter reaching target HR, then FU according to a preset schedule (at 1, 2, 3 months after initial treatment, then every 3 months until 36 months); Other Names: EBL+Beta blocker

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
First esophageal variceal bleeding	First esophageal variceal bleeding after enrollment	3 years after enrollment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality; Significant esophageal variceal bleeding; Upper gastrointestinal bleeding except esophageal bleeding; Adverse events	Mortality; Significant esophageal variceal bleeding; Upper gastrointestinal bleeding except esophageal bleeding; Adverse events	3 years after enrollment

Collaborators and Investigators

• Sponsor: Korea University
• Investigators: Principal Investigator: Soon Ho Um, Prof, Korea University

Study record dates

Study Major Dates

• Study Start: September 1, 2006
• Primary Completion (Anticipated): May 1, 2019
• Study Completion (Anticipated): May 1, 2021

Study Registration Dates

• First Submitted: August 25, 2009
• First Submitted That Met QC Criteria: August 25, 2009
• First Posted (Estimate): August 26, 2009

Study Record Updates

• Last Update Posted (Actual): August 23, 2017
• Last Update Submitted That Met QC Criteria: August 22, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Keywords: Cirrhosis; Varicose Veins; Esophagus Disorders
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Liver Diseases; Fibrosis; Hemorrhage; Liver Cirrhosis; Physiological Effects of Drugs; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Vasodilator Agents; Propranolol; Adrenergic beta-Antagonists
• Other Study ID Numbers: RCTPEBL