Therapeutic Approach to Diastolic Dysfunction in Chronic Liver Disease Patients and Its Impact on Morbidity and Mortality

Study Overview
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Brief Summary
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Cirrhotic cardiomyopathy is defined as a chronic cardiac dysfunction in patients with cirrhosis. It is suspected that this specific cardiac dysfunction contributes to the onset of complications in liver disease. The purpose of this prospective, randomized controlled trial is to determine whether carvedilol can revert cardiac dysfunction i.e. left ventricular diastolic dysfunction secondary to cirrhosis, and prevent complications (renal dysfunction, worsening cardiac function, and mortality).

Official Title
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Therapeutic Approach to Diastolic Dysfunction in Chronic Liver Disease Patients and Its' Impact on Morbidity and Mortality

Conditions
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Diastolic Dysfunction, Chronic Liver Disease

Intervention / Treatment
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* Drug: Carvedilol
* Drug: Ivabradine
* Procedure: Endoscopic Variceal Ligation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with cirrhosis who have been diagnosed by clinical, biochemical,or histological (when available) criteria plus ultrasound imaging. Age range of 18-60 years Cirrhosis as diagnosed by histology or clinical, laboratory and USG (UltraSonography) findings, Upper GI bleed who are undergoing secondary endoscopic variceal ligation for eradication of varices Exclusion Criteria: Age >60 years Chronic renal disease Pregnancy and peripartum cardiomyopathy Hypertension Coronary artery disease Valvular heart disease Sick sinus syndrome/ Pacemaker Cardiac rhythm disorder Hypothyroidism Hyperthyroidism Portal vein thrombosis Transjugular intrahepatic porto systemic shunt (TIPS) insertion Hepatocellular carcinoma Anemia Hb < 8gm/dl in females, and < 9 gm/dl in males

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Carvedilol + Ivabradine<br>Carvedilol started to achieve target HR (heart rate) reduction to 60/min, to a lowest permissible 50-55/ min ; provided Systolic Blood Pressure> 90 mmHg. if carvedilol is not tolerated,Ivabradine is added in a dose starting 2.5 mg BD to a maximum of 15 mg/day to ensure targeted heart rate reduction | Drug: Carvedilol<br>* Carvedilol started to achieve target HR (heart rate) reduction to 60/min, to a lowest permissible 50-55/ min ; provided Systolic Blood Pressure> 90 mmHg.<br>Drug: Ivabradine<br>* Carvedilol started to achieve target HR (heart rate) reduction to 60/min, to a lowest permissible 50-55/ min ; provided Systolic Blood Pressure> 90 mmHg. If carvedilol is not tolerated,Ivabradine is added in a dose starting 2.5 mg BD to a maximum of 15 mg/day to ensure targeted heart rate reduction<br>|
| Active Comparator: Endoscopic Variceal Ligation (EVL)<br> | Procedure: Endoscopic Variceal Ligation<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression of cirrhosis and its complications. |  | 1 Year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement in left ventricular diastolic function in either arm. |  | 1 Year | 
| Renal function | Renal function is being checked- urea, creatinine, urine sediment, and creatinine clearance as calculated by Cockcroft - Gault formula | 1 Year | 
| Serum level of Brain Natriuretic Peptide. |  | 1 Year | 
| Mortality |  | 1 Year | 
| Quality of life |  | 1 Year | 
| Electrophysiologic modifications | Electrophysiological changes checked are QTc interval, documentation of arrhythmias | 1 Year | 
| Serum level of catecholamines |  | 1 year | 
| Serum level of plasma renin activity |  | 1 Year |