Early Primary Prophylaxis of Esophageal Varices

Study Overview
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Brief Summary
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Patients of cirrhosis with portal hypertension aged 18 to 75 years who have small esophageal varices with or without red color signs and have not bled previously will be enrolled. After baseline evaluation, the participants will be randomized to receive either Placebo or Carvedilol 12.5 mg BD. After randomization they will be followed up for one year. The primary endpoint of the study is the the proportions of patients who develop large varices (Gd 3 or Gd 4) at 1 year in each group. The secondary endpoint are survival,reduction in HVPG,change in CTP and MELD score& adverse events.

Official Title
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A Prospective, Double-blind, Randomized Placebo-controlled Trial of Carvedilol for Early Primary Prophylaxis of Esophageal Varices in Cirrhosis.

Conditions
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Cirrhosis

Intervention / Treatment
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* Drug: Carvedilol
* Drug: Placebo


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 small esophageal varices with or without red color signs and have not bled previously. Exclusion Criteria: Any contra-indication to beta-blockers Any EVL or sclerotherapy within last 3 months Child Turcotte Pugh (CTP) score > 12, refractory ascites, hepatorenal syndrome Any past history of surgery for portal hypertension Significant cardio or pulmonary co-morbidity Any malignancy that affects survival. Active alcohol abuse or last intake ≤ 4 weeks to avoid possibility of ongoing alcohol hepatitis. Past history of surgery for portal hypertension Uncontrolled diabetes Peripheral vascular disease 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Carvedilol<br>Tablet Carvedilol 12.5 mg BD or maximum tolerated dose | Drug: Carvedilol<br>* Carvedilol will be administered orally at a start dose of 3.125 mg twice daily. After 1 week, this will increased if systolic blood pressure does not fall below 90 mm Hg. The patient will receive the maximum tolerated dose of carvedilol or with a maximum of 12.5 BD.<br>|
| Placebo Comparator: Placebo<br>Placebo tablets 2 to 4 BD | Drug: Placebo<br>* The placebo tablets will be identical to the carvedilol tablets. First the patients will receive placebo in the dose of 1 BD. Then depending on his tolerance it will be increased to a maximum of 4 BD.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary endpoint of the study is the the proportions of patients who develop large varices (Gd 3 or Gd 4) during the period of 2 year in each group. |  | 2 Years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival |  | 2 Years | 
| adverse effects of drugs |  | 2 Years | 
| reduction in HVPG |  | 1 Year |