Carvedilol + VSL#3 Versus Endoscopic Variceal Ligation for Primary Prophylaxis of Esophageal Variceal Bleeding in Cirrhotic Patients Non Responder to Carvedilol.

Study Overview
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Brief Summary
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Patients of cirrhosis will be enrolled who have large esophageal varices, which have never bled. After successful screening baseline hepatic venous pressure gradient (HVPG) will be measured. Tablet carvedilol 3.125 mg BD for 1 week will be started. It will be increased to 6.25 mg BD and continued for next 7 weeks. After completion of 8 weeks the hepatic venous pressure gradient (HVPG) will again be measured to find out responders (hepatic venous pressure gradient ≥20% reduction from baseline or absolute value of hepatic venous pressure gradient <12 mm Hg) and non responders (hepatic venous pressure gradient <20% reduction).The responders will be excluded from the study while the non responders will be randomize into carvedilol+VSL#3 versus Endoscopic Variceal Ligation.

Official Title
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A Prospective,Open Labeled, Randomized Controlled Trial Comparing Carvedilol + VSL# 3 Versus Endoscopic Variceal Ligation for Primary Prophylaxis of Esophageal Variceal Bleeding in Cirrhotic Patients Non Responder to Carvedilol.

Conditions
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Cirrhosis

Intervention / Treatment
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* Drug: Carvedilol+VSL#3
* Procedure: Endoscopic variceal ligation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients of cirrhosis with portal hypertension aged 18 to 75 years who have large esophageal varices with or without red color signs and have not bled previously. Exclusion Criteria: Any contra-indication to beta-blockers Coagulopathy with INR >1.8 at the time of enrollment Any Endoscopic Variceal Ligation or sclerotherapy within last 3 months Any past history of surgery for portal hypertension Significant cardio or pulmonary co-morbidity Any malignancy Refusal to participate in the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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 |
| --- | --- |
| Experimental: Carvedilol+VSL#3<br>Tablet Carvedilol 6.25 mg BD + VSL#3 | Drug: Carvedilol+VSL#3<br>* Tablet Carvedilol 6.25 mg BD & capsule VSL#3 1 TDS for 2 year<br>|
| Active Comparator: Endoscopic Variceal Ligation<br>Endoscopic Variceal Ligation every 3-4 weeks till variceal ligation | Drug: Carvedilol+VSL#3<br>* Tablet Carvedilol 6.25 mg BD & capsule VSL#3 1 TDS for 2 year<br>Procedure: Endoscopic variceal ligation<br>* In the Endoscopic Variceal Ligation arm, Endoscopic Variceal Ligation will be performed using multibander devices by senior fully trained endoscopists or under their direct supervision. Varices will be banded starting at the gastroesophageal junction moving proximally upward in a spiral fashion. Patients will undergo Endoscopic Variceal Ligation every 3-4 weeks until eradication. Eradication is defined as the absence of varices or presence of grade I esophageal varices. Following eradication, the interval for the next endoscopy will be every 3 months to look for recurrence of varices. Endoscopic Variceal Ligation sessions would be repeated for the recurrent varices if they are sufficiently large.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Development of first variceal bleeding |  | 1 Year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival |  | 1 Year | 
| Reduction in Portal pressure |  | 1 Year | 
| Time to bleed |  | 1 Years | 
| Adverse events |  | 1 Year |