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

Primary Purpose

Diastolic Dysfunction, Chronic Liver Disease

Status
Completed
Phase
Not Applicable
Locations
India
Study Type
Interventional
Intervention
Carvedilol
Ivabradine
Endoscopic Variceal Ligation
Sponsored by
Institute of Liver and Biliary Sciences, India
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Diastolic Dysfunction

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Institute of Liver & Biliary Sciences

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Carvedilol + Ivabradine

Endoscopic Variceal Ligation (EVL)

Arm Description

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

Outcomes

Primary Outcome Measures

Progression of cirrhosis and its complications.

Secondary Outcome Measures

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

Full Information

First Posted
June 9, 2014
Last Updated
February 6, 2018
Sponsor
Institute of Liver and Biliary Sciences, India
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1. Study Identification

Unique Protocol Identification Number
NCT02294292
Brief Title
Therapeutic Approach to Diastolic Dysfunction in Chronic Liver Disease Patients and Its Impact on Morbidity and Mortality
Official Title
Therapeutic Approach to Diastolic Dysfunction in Chronic Liver Disease Patients and Its' Impact on Morbidity and Mortality
Study Type
Interventional

2. Study Status

Record Verification Date
February 2016
Overall Recruitment Status
Completed
Study Start Date
July 1, 2014 (Actual)
Primary Completion Date
August 31, 2016 (Actual)
Study Completion Date
August 31, 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Institute of Liver and Biliary Sciences, India

4. Oversight

Data Monitoring Committee
No

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diastolic Dysfunction, Chronic Liver Disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
Participant
Allocation
Randomized
Enrollment
189 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Carvedilol + Ivabradine
Arm Type
Experimental
Arm Description
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
Arm Title
Endoscopic Variceal Ligation (EVL)
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
Carvedilol
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Ivabradine
Intervention Description
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
Intervention Type
Procedure
Intervention Name(s)
Endoscopic Variceal Ligation
Primary Outcome Measure Information:
Title
Progression of cirrhosis and its complications.
Time Frame
1 Year
Secondary Outcome Measure Information:
Title
Improvement in left ventricular diastolic function in either arm.
Time Frame
1 Year
Title
Renal function
Description
Renal function is being checked- urea, creatinine, urine sediment, and creatinine clearance as calculated by Cockcroft - Gault formula
Time Frame
1 Year
Title
Serum level of Brain Natriuretic Peptide.
Time Frame
1 Year
Title
Mortality
Time Frame
1 Year
Title
Quality of life
Time Frame
1 Year
Title
Electrophysiologic modifications
Description
Electrophysiological changes checked are QTc interval, documentation of arrhythmias
Time Frame
1 Year
Title
Serum level of catecholamines
Time Frame
1 year
Title
Serum level of plasma renin activity
Time Frame
1 Year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Facility Information:
Facility Name
Institute of Liver & Biliary Sciences
City
New Delhi
State/Province
Delhi
ZIP/Postal Code
110070
Country
India

12. IPD Sharing Statement

Citations:
PubMed Identifier
31305281
Citation
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.
Results Reference
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Therapeutic Approach to Diastolic Dysfunction in Chronic Liver Disease Patients and Its Impact on Morbidity and Mortality

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