Ivabradine in Cirrhotic Cardiomyopathy

NCT04111133 | Recruiting DMC

• 1 other identifier: INT/IEC/2019/001617
• Study Type: interventional
• Target: 130
• Locations: 1 country
• Sites: 1

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.

Conditions

Cirrhotic Cardiomyopathy; Left Ventricular Dysfunction; Cirrhosis, Liver; Portal Hypertension

Keywords

Cirrhotic cardiomyopathy; Left ventricular diatolic dysfunction; Carvedilol; Ivabradine

Outcome Measures

Primary Outcomes (1)

• Survival

  All cause mortality to be assessed

  12 months

Secondary Outcomes (5)

• Change in E/e' Ratio

  12 months

• Change in renal function

  12 months

• Change in HRQoL

  12 months

• Change in neurohormonal markers- Brain natriuretic peptide, aldosterone, plasma renin activity

  12 months

• Number of Episodes of Cirrhosis related events

  12 months

Study Arms (2)

Carvedilol + Ivabradine

EXPERIMENTAL

Drug: Betablocker + ivabradine

Carvedilol

ACTIVE COMPARATOR

Drug: Betablocker

Interventions

Betablocker + ivabradine DRUG

Use of maximum tolerated dose of carvedilol and ivabradine to achieve therapeutic heart rate reduction (THR) to 55-65 beats per minute

Carvedilol + Ivabradine

Betablocker DRUG

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.

Carvedilol

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age range of 18-65 years
• Cirrhosis, as diagnosed by histology or clinical, laboratory and USG findings,
• LV diastolic dysfunction on 2D echocardiography

You may not qualify if:

• 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

Sponsors & Collaborators

• Post Graduate Institute of Medical Education and Research, Chandigarh: lead

Study Sites (1)

Postgraduate Institute of Medical Education and Research

Chandigarh, Choose Any State/Province, 160012, India

RECRUITING

Related Publications (3)

• Izzy M, VanWagner LB, Lin G, Altieri M, Findlay JY, Oh JK, Watt KD, Lee SS; Cirrhotic Cardiomyopathy Consortium. Redefining Cirrhotic Cardiomyopathy for the Modern Era. Hepatology. 2020 Jan;71(1):334-345. doi: 10.1002/hep.30875. Epub 2019 Oct 11.

  PMID: 31342529 RESULT

• 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.

  PMID: 31305281 RESULT

• Kaur H, Premkumar M. Diagnosis and Management of Cirrhotic Cardiomyopathy. J Clin Exp Hepatol. 2022 Jan-Feb;12(1):186-199. doi: 10.1016/j.jceh.2021.08.016. Epub 2021 Aug 21.

  PMID: 35068798 RESULT

MeSH Terms

Conditions

Ventricular Dysfunction, Left; Liver Cirrhosis; Hypertension, Portal

Interventions

Ivabradine

Condition Hierarchy (Ancestors)

Ventricular Dysfunction; Heart Diseases; Cardiovascular Diseases; Liver Diseases; Digestive System Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Radha K Dhiman, MD DM

  Post Graduate Institute of Medical Education and Research, Chandigarh

  STUDY CHAIR

Central Study Contacts

Madhumita Premkumar, MD DM

CONTACT

01722756344; drmadhumitap@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Open Label
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor and Principal Investigator, Department of Hepatology

Study Record Dates

• First Submitted: September 26, 2019
• First Posted: October 1, 2019
• Study Start: January 1, 2020
• Primary Completion: October 1, 2024
• Study Completion: December 1, 2024
• Last Updated: February 13, 2024

Record last verified: 2024-02

Locations

IN (1)