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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Cirrhosis, Variceal Bleeding

Intervention / Treatment
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* Procedure: Endoscopic band ligation
* Drug: Propranolol
* Procedure: EBL+Propranolol


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Endoscopic band ligation<br>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<br>* 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).<br>* Other names: EBL;|
| Active Comparator: Propranolol<br>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<br>* 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)<br>* Other names: Beta blocker;|
| Active Comparator: EBL+Propranolol<br>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<br>* EBL 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). Propranolol start with 20 mg 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)<br>* Other names: EBL+Beta blocker;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cirrhosis, Esophagus Disorders, Varicose Veins