Ivabradine in Cirrhotic Cardiomyopathy

• Sponsor: Postgraduate Institute of Medical Education and Research (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT04111133
• Collaborator: (none)
• Enrollment: 130
• Location: 1
• Arms: 2
• Anticipated Duration (Months): 47
• Patients Per Site Per Month: 2.8

Study Details

Study Description

Brief Summary

A total of 130 patients with liver cirrhosis who fulfill the criteria of the study, and who have been found to have left ventricular diastolic dysfunction on a screening 2D echocardiography, will then be randomized by Block randomization technique, to two arms in a ratio 1:1(Group A) will receive carvedilol+ Ivabradine targeted therapy for heart rate reduction while Group B will receive Carvedilol alone; and the dosage of drug in the treatment arm will be titrated every week to achieve target heart rate of 50-60/ minute. Patients in the treatment arms, who are unable to tolerate carvedilol due to hypotension episodes, will be offered ivabradine alone to allow achievement of targeted heart rate reduction. All patients will be evaluated at 0,6, and 12 months. The end points will be clinical events, cardiac function improvement, renal function, and mortality.

Condition or Disease	Intervention/Treatment	Phase
Cirrhotic Cardiomyopathy; Left Ventricular Dysfunction; Cirrhosis, Liver; Portal Hypertension	Drug: Betablocker + ivabradine; Drug: Betablocker	N/A

Detailed Description

The investigators have already demonstrated the role of targeted heart rate reduction in the management of LVDD in cirrhosis, but the previous study could not demonstrate the role of ivabradine alone in absence of betablocker therapy. This trial will be a validation cohort for the initial data obtained on this novel drug. The use of ivabradine can treat patients who do not tolerate betablocker therapy due to contraindications or adverse effects especially hypotension.

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 130 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Masking Description: Open Label
• Primary Purpose: Treatment
• Official Title: Efficacy of Carvedilol + Ivabradine vs Carvedilol Alone for Left Ventricular Diastolic Dysfunction in Chronic Liver Disease Patients and Its' Impact on Morbidity and Mortality; a Prospective Randomized Controlled Trial.
• Actual Study Start Date: Jan 1, 2020
• Anticipated Primary Completion Date: Oct 1, 2023
• Anticipated Study Completion Date: Dec 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Carvedilol + Ivabradine	Drug: Betablocker + ivabradine; Use of maximum tolerated dose of carvedilol and ivabradine to achieve therapeutic heart rate reduction (THR) to 55-65 beats per minute
Active Comparator: Carvedilol	Drug: Betablocker; Use of maximum tolerated dose of carvedilol to achieve targeted heart rate reduction (THR) to 55-65 beats per minute (responder) or inability to reach THR (non responder) with maximum dose of carvedilol, maintaining a minimum MAP of 70 mmHg.

Outcome Measures

Primary Outcome Measures

1. Number of Episodes of Cirrhosis related events [12 months]

   New onset ascites, variceal bleeding,hepatorenal syndrome

2. Survival [12 months]

   All cause mortality to be assessed

Secondary Outcome Measures

1. Change in E/e' Ratio [12 months]

   Echo parameter to be documented

2. Change in renal function [12 months]

3. Change in HRQoL [12 months]

4. Change in neurohormonal markers- Brain natriuretic peptide, aldosterone, plasma renin activity [12 months]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Age range of 18-65 years

• Cirrhosis, as diagnosed by histology or clinical, laboratory and USG findings,

• LV diastolic dysfunction on 2D echocardiography

Exclusion Criteria:

• Chronic renal disease

• Patient already on beta blocker

• 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Postgraduate Institute of Medical Education and Research	Chandigarh	Choose Any State/Province	India	160012

Sponsors and Collaborators

• Postgraduate Institute of Medical Education and Research

Investigators

• Study Chair: Radha K Dhiman, MD DM, Postgraduate Institute of Medical Education and Research

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Madhumita Premkumar, Assistant Professor and Principal Investigator, Department of Hepatology, Postgraduate Institute of Medical Education and Research
• ClinicalTrials.gov Identifier: NCT04111133
• Other Study ID Numbers: INT/IEC/2019/001617
• First Posted: Oct 1, 2019
• Last Update Posted: Aug 3, 2022
• Last Verified: Aug 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by Madhumita Premkumar, Assistant Professor and Principal Investigator, Department of Hepatology, Postgraduate Institute of Medical Education and Research: Cirrhotic cardiomyopathy; Left ventricular diatolic dysfunction; Carvedilol; Ivabradine
• Additional relevant MeSH terms: Hypertension, Portal; Liver Cirrhosis; Cardiomyopathies; Ventricular Dysfunction; Ventricular Dysfunction, Left; Adrenergic beta-Antagonists

Study Results

No Results Posted as of Aug 3, 2022