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Ivabradine in Cirrhotic Cardiomyopathy

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04111133
Recruitment Status : Recruiting
First Posted : October 1, 2019
Last Update Posted : January 27, 2020
Sponsor:
Information provided by (Responsible Party):
Madhumita Premkumar, Postgraduate Institute of Medical Education and Research

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 Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Estimated 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.
Estimated Study Start Date : February 1, 2020
Estimated Primary Completion Date : October 2021
Estimated Study Completion Date : October 2022


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.




Primary Outcome Measures :
  1. Number of Episodes of Cirrhosis related events [ Time Frame: 12 months ]
    New onset ascites, variceal bleeding,hepatorenal syndrome

  2. Survival [ Time Frame: 12 months ]
    All cause mortality to be assessed


Secondary Outcome Measures :
  1. Improvement in E/e' Ratio [ Time Frame: 12 months ]
    Improved Echo parameter

  2. Improvement in renal function [ Time Frame: 12 months ]
  3. Improvement in HRQoL [ Time Frame: 12 months ]
  4. Improvement in neurohormonal markers- Brain natriuretic peptide, aldosterone, plasma renin activity [ Time Frame: 12 months ]


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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04111133


Contacts
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Contact: Madhumita Premkumar, MD DM 01722756344 drmadhumitap@gmail.com

Locations
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India
Postgraduate Institute of Medical Education and Research Recruiting
Chandigarh, Choose Any State/Province, India, 160012
Contact: Madhumita Premkumar         
Sponsors and Collaborators
Postgraduate Institute of Medical Education and Research
Investigators
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Study Chair: Radha K Dhiman, MD DM Postgraduate Institute of Medical Education and Research
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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: October 1, 2019    Key Record Dates
Last Update Posted: January 27, 2020
Last Verified: January 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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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, Postgraduate Institute of Medical Education and Research:
Cirrhotic cardiomyopathy
Left ventricular diatolic dysfunction
Carvedilol
Ivabradine
Additional relevant MeSH terms:
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Hypertension, Portal
Liver Cirrhosis
Cardiomyopathies
Ventricular Dysfunction
Ventricular Dysfunction, Left
Cardiovascular Diseases
Heart Diseases
Liver Diseases
Digestive System Diseases
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs