To Compare the Efficacy and Safety of Carvedilol With or Without Simvastatin in Patients With Portal Hypertension and Esophageal Varices.

Study Overview
=================
Brief Summary
-----------------
After successful screening of patients based on inclusion criteria, we will measure the baseline Hepatic Venous Pressure Gradient. At day 1 patients will undergo complete blood investigation including complete haemogram, kidney function test, liver function test, prothrombin time, AFP (Alfa Feto Protein) level, chest x ray, ultrasonography, fibroscan. Routine complete physical examination will be done.

Official Title
-----------------
A Prospective Randomized Study to Compare the Efficacy and Safety of Carvedilol With or Without Simvastatin in Patients With Portal Hypertension and Esophageal Varices

Conditions
-----------------
Cirrhosis With Esophageal Varices

Intervention / Treatment
-----------------
* Drug: Carvedilol
* Drug: Carvedilol + Simvastatin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: All patients of chronic liver disease with esophageal varices. Age more than and equal to 18 years. Exclusion Criteria: Patients of chronic liver disease with history of upper Gastro Intestinal bleed. Patients of acute on chronic liver failure Thrombosis of splenoportal axis Hepatocellular carcinoma Patients who were on primary variceal ligation sessions as prophylaxis Patients who are beta blocker intolerant (Prior h/o hypotension, bradycardia). Patients who are contraindicated for beta blockers {H/O COPD (Coronary Obstructive Pulmonary Disease), heart block, refractory Ascites, SBP(Spontaneous Bacterial Peritonitis) , HRS(Hepato Renal Syndrome)}. Failure to give consent for inclusion in the study

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Carvedilol + Simvastatin<br>Carvedilol will be administered orally at a start dose of 3.125 mg twice daily per day. After 1 week, this will increased to a dose of 6.25 mg twice daily per day. Target dose of 12.5 mg twice daily per day will be started after 2 weeks if systolic blood pressure does not fall below 90 mm Hg and HR 55-60/min. Simvastatin will be administered orally at a start dose of 20 mg for 15 days followed by 40 mg OD for the next 3 months. Along with Simvastatin, Carvedilol will be administered orally at a start dose of 3.125 mg twice daily per day. After 1 week, this will increased to a dose of 6.25 mg twice daily per day. Target dose of 12.5 mg twice daily per day will be started after 2 weeks if systolic blood pressure does not fall below 90 mm Hg and HR 55-60/min. | Drug: Carvedilol + Simvastatin<br> <br> |
| Active Comparator: Carvedilol<br>Carvedilol will be administered orally at a start dose of 3.125 mg twice daily per day. After 1 week, this will increased to a dose of 6.25 mg twice daily per day. Target dose of 12.5 mg twice daily per day will be started after 2 weeks if systolic blood pressure does not fall below 90 mm Hg and HR 55-60/min. | Drug: Carvedilol<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total number of patients who will be Responders. | Responders (Absolute value of HVPG<12 mm Hg or HVPG≥20% reduction) | 3 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total number of patients develop esophageal variceal bleed |  | 3 months | 
| Total number of patients develop PHG (Portal Hypertensive Gastropathy). |  | 3 months | 
| Total number of patients develop GAVE (Gastric Antral Vascular Ectasia). |  | 3 months | 
| Total number of patients develop Gastric Varices. |  | 3 months | 
| Total number of patients develop adverse Events of the study drug |  | 3 months | 
| Improvement in the CTP (Child-Turcotte-Pugh score) score. |  | 3 months | 
| Improvement in the MELD (Model for End Stage liver Disease) score. |  | 3 months |