Ivabradine in Cirrhotic Cardiomyopathy

NCT ID: NCT04111133

Last Updated: 2024-02-13

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 130 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-01-01
• Study Completion Date: 2024-12-31

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.

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.

Diagnosis of CCM will be as per 2020 CCMC criteria. CCM is defined as systolic or diastolic dysfunction in the absence of alternative cardiac pathology in concordance with the Cirrhotic Cardiomyopathy Consortium (CCMC) criteria. 9 Systolic dysfunction was defined as an ejection fraction (EF) ≤50% or an absolute value of GLS <18%. CCM will defined as presence of 3 of the following 4 criteria: septal early diastolic mitral annular flow velocity (e') <7 cm/s, early diastolic transmitral flow to early diastolic mitral annular velocity (E/e') ≥15, left atrial volume index (LAVI) >34 mL/m2, tricuspid jet maximum velocity >2.8 m/s, in the absence of pulmonary hypertension and the presence of measurable early to late diastolic transmitral flow velocity (E/A) ratio (E/A >2 = grade 3 & E/A 0.8-2 = grade 2 LVDD). Persons meeting only 2 criteria will be termed as indeterminate for LVDD grade.

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Carvedilol + Ivabradine

Group Type: EXPERIMENTAL

Betablocker + ivabradine

Intervention Type: DRUG

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

Carvedilol

Group Type: ACTIVE_COMPARATOR

Betablocker

Intervention Type: 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.

Interventions

Betablocker + ivabradine

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

Intervention Type: 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.

Intervention Type: DRUG

Eligibility 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Post Graduate Institute of Medical Education and Research, Chandigarh

OTHER

Sponsor Role: lead

Responsible Party

Madhumita Premkumar

Assistant Professor and Principal Investigator, Department of Hepatology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Radha K Dhiman, MD DM

Role: STUDY_CHAIR

Post Graduate Institute of Medical Education and Research, Chandigarh

Locations

Postgraduate Institute of Medical Education and Research

Chandigarh, Choose Any State/Province, India

Site Status: RECRUITING

Countries

India

Central Contacts

Madhumita Premkumar, MD DM

Role: CONTACT

drmadhumitap@gmail.com

01722756344

Facility Contacts

Madhumita Premkumar

Role: primary

References

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.

Reference Type: RESULT

PMID: 31342529 (View on PubMed)

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.

Reference Type: RESULT

PMID: 31305281 (View on PubMed)

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.

Reference Type: RESULT

PMID: 35068798 (View on PubMed)

Other Identifiers

INT/IEC/2019/001617

Identifier Type: -

Identifier Source: org_study_id