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

Not Applicable

Completed

• Conditions: Chronic Liver Disease; Diastolic Dysfunction
• Interventions: Procedure: Endoscopic Variceal Ligation; Drug: Carvedilol; Drug: Ivabradine

• Registration Number: NCT02294292
• Lead Sponsor: Institute of Liver and Biliary Sciences, India

Brief Summary

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).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2014-06-09
• Study Start: 2014-07-01
• Study First Submitted QC: 2014-11-18
• Study First Posted: 2014-11-19
• Status Verified: 2016-02
• Primary Completion: 2016-08-31
• Study Completion: 2016-08-31
• Last Update Submitted: 2018-02-06
• Last Update Posted: 2018-02-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 189

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Endoscopic Variceal Ligation (EVL)	Endoscopic Variceal Ligation	-
Carvedilol + Ivabradine	Carvedilol	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
Carvedilol + Ivabradine	Ivabradine	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

Primary Outcome Measures

Name	Time	Method
Progression of cirrhosis and its complications.	1 Year

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Institute of Liver & Biliary Sciences; 🇮🇳 New Delhi, Delhi, India