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

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

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.

Study Overview

• Status: Completed
• Conditions: Cirrhosis With Esophageal Varices
• Intervention / Treatment: Drug: Carvedilol; Drug: Carvedilol + Simvastatin

• Study Type: Interventional
• Enrollment (Actual): 220
• Phase: Not Applicable

Contacts and Locations

Study Locations

• India
  • Delhi
    • New Delhi, Delhi, India, 110070
      • Institute of Liver and Biliary Sciences

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. All patients of chronic liver disease with esophageal varices.
2. Age more than and equal to 18 years.

Exclusion Criteria:

1. Patients of chronic liver disease with history of upper Gastro Intestinal bleed.
2. Patients of acute on chronic liver failure
3. Thrombosis of splenoportal axis
4. Hepatocellular carcinoma
5. Patients who were on primary variceal ligation sessions as prophylaxis
6. Patients who are beta blocker intolerant (Prior h/o hypotension, bradycardia).
7. 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)}.
8. Failure to give consent for inclusion in the study

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Carvedilol + 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. 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
Active Comparator: Carvedilol; 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

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	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

Collaborators and Investigators

• Sponsor: Institute of Liver and Biliary Sciences, India
• Investigators: Principal Investigator: Dr V Rajan, MD, Institute of Liver and Biliary Sciences

Publications and helpful links

General Publications

• Vijayaraghavan R, Jindal A, Arora V, Choudhary A, Kumar G, Sarin SK. Hemodynamic Effects of Adding Simvastatin to Carvedilol for Primary Prophylaxis of Variceal Bleeding: A Randomized Controlled Trial. Am J Gastroenterol. 2020 May;115(5):729-737. doi: 10.14309/ajg.0000000000000551.

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2015
• Primary Completion (Actual): January 31, 2017
• Study Completion (Actual): January 31, 2017

Study Registration Dates

• First Submitted: June 4, 2015
• First Submitted That Met QC Criteria: June 4, 2015
• First Posted (Estimate): June 8, 2015

Study Record Updates

• Last Update Posted (Actual): May 11, 2018
• Last Update Submitted That Met QC Criteria: May 10, 2018
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Cardiovascular Diseases; Vascular Diseases; Gastrointestinal Diseases; Liver Diseases; Esophageal Diseases; Hypertension; Esophageal and Gastric Varices; Hypertension, Portal; Varicose Veins; Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Vasodilator Agents; Enzyme Inhibitors; Antimetabolites; Protective Agents; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Membrane Transport Modulators; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Antioxidants; Adrenergic alpha-1 Receptor Antagonists; Adrenergic alpha-Antagonists; Simvastatin; Carvedilol
• Other Study ID Numbers: ILBS-Cirrhosis-004