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

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

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).

Study Overview

• Status: Completed
• Conditions: Chronic Liver Disease; Diastolic Dysfunction
• Intervention / Treatment: Drug: Carvedilol; Drug: Ivabradine; Procedure: Endoscopic Variceal Ligation

• Study Type: Interventional
• Enrollment (Actual): 189
• Phase: Not Applicable

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Carvedilol + 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	Drug: 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.; Drug: 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
ACTIVE_COMPARATOR: Endoscopic Variceal Ligation (EVL)	Procedure: Endoscopic Variceal Ligation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Institute of Liver and Biliary Sciences, India

Publications and helpful links

General Publications

• Premkumar M, Rangegowda D, Vyas T, Khumuckham JS, Shasthry SM, Thomas SS, Goyal R, Kumar G, Sarin SK. Carvedilol Combined With Ivabradine Improves Left Ventricular Diastolic Dysfunction, Clinical Progression, and Survival in Cirrhosis. J Clin Gastroenterol. 2020 Jul;54(6):561-568. doi: 10.1097/MCG.0000000000001219.

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 1, 2014
• Primary Completion (ACTUAL): August 31, 2016
• Study Completion (ACTUAL): August 31, 2016

Study Registration Dates

• First Submitted: June 9, 2014
• First Submitted That Met QC Criteria: November 18, 2014
• First Posted (ESTIMATE): November 19, 2014

Study Record Updates

• Last Update Posted (ACTUAL): February 8, 2018
• Last Update Submitted That Met QC Criteria: February 6, 2018
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Vasodilator Agents; Protective Agents; Membrane Transport Modulators; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Antioxidants; Adrenergic alpha-1 Receptor Antagonists; Adrenergic alpha-Antagonists; Carvedilol
• Other Study ID Numbers: ILBS-CLD-DD-01