Ivabradine in Cirrhotic Cardiomyopathy

Post Graduate Institute of Medical Education and Research, Chandigarh

Status: Enrolling

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

Treatments: Drug: Betablocker; Drug: Betablocker + ivabradine

Study type: Interventional

Funder types: Other

Identifiers

NCT04111133

INT/IEC/2019/001617

Details and patient eligibility

About

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.

Full 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.

Enrollment: 130 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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130 participants in 2 patient groups

Carvedilol + Ivabradine

Experimental group

Treatment:

Drug: Betablocker + ivabradine

Carvedilol

Active Comparator group

Treatment:

Drug: Betablocker