NCT02294292

Brief Summary

Cirrhotic cardiomyopathy is defined as a chronic cardiac dysfunction in patients with cirrhosis. It is suspected that this specific cardiac dysfunction contributes to the onset of complications in liver disease. The purpose of this prospective, randomized controlled trial is to determine whether carvedilol can revert cardiac dysfunction i.e. left ventricular diastolic dysfunction secondary to cirrhosis, and prevent complications (renal dysfunction, worsening cardiac function, and mortality).

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
189

participants targeted

Target at P75+ for not_applicable

Timeline
Completed

Started Jul 2014

Typical duration for not_applicable

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

June 9, 2014

Completed
22 days until next milestone

Study Start

First participant enrolled

July 1, 2014

Completed
5 months until next milestone

First Posted

Study publicly available on registry

November 19, 2014

Completed
1.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 31, 2016

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

August 31, 2016

Completed
Last Updated

February 8, 2018

Status Verified

February 1, 2016

Enrollment Period

2.2 years

First QC Date

June 9, 2014

Last Update Submit

February 6, 2018

Conditions

Diastolic DysfunctionChronic Liver Disease

Outcome Measures

Primary Outcomes (1)

  • Progression of cirrhosis and its complications.

    1 Year

Secondary Outcomes (8)

  • Improvement in left ventricular diastolic function in either arm.

    1 Year

  • Renal function

    1 Year

  • Serum level of Brain Natriuretic Peptide.

    1 Year

  • Mortality

    1 Year

  • Quality of life

    1 Year

  • +3 more secondary outcomes

Study Arms (2)

Carvedilol + Ivabradine

EXPERIMENTAL

Carvedilol started to achieve target HR (heart rate) reduction to 60/min, to a lowest permissible 50-55/ min ; provided Systolic Blood Pressure\> 90 mmHg. if carvedilol is not tolerated,Ivabradine is added in a dose starting 2.5 mg BD to a maximum of 15 mg/day to ensure targeted heart rate reduction

Drug: CarvedilolDrug: Ivabradine

Endoscopic Variceal Ligation (EVL)

ACTIVE COMPARATOR
Procedure: Endoscopic Variceal Ligation

Interventions

CarvedilolDRUG

Carvedilol started to achieve target HR (heart rate) reduction to 60/min, to a lowest permissible 50-55/ min ; provided Systolic Blood Pressure\> 90 mmHg.

Carvedilol + Ivabradine
IvabradineDRUG

Carvedilol started to achieve target HR (heart rate) reduction to 60/min, to a lowest permissible 50-55/ min ; provided Systolic Blood Pressure\> 90 mmHg. If carvedilol is not tolerated,Ivabradine is added in a dose starting 2.5 mg BD to a maximum of 15 mg/day to ensure targeted heart rate reduction

Carvedilol + Ivabradine
Endoscopic Variceal LigationPROCEDURE
Endoscopic Variceal Ligation (EVL)

Eligibility Criteria

Age18 Years - 60 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64)

You may qualify if:

  • Patients with cirrhosis who have been diagnosed by clinical, biochemical,or histological (when available) criteria plus ultrasound imaging.
  • Age range of 18-60 years
  • Cirrhosis as diagnosed by histology or clinical, laboratory and USG (UltraSonography) findings,
  • Upper GI bleed who are undergoing secondary endoscopic variceal ligation for eradication of varices

You may not qualify if:

  • Age \>60 years
  • Chronic renal disease
  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Institute of Liver & Biliary Sciences

New Delhi, National Capital Territory of Delhi, 110070, India

Location

Related Publications (1)

  • 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: 31305281DERIVED

MeSH Terms

Interventions

CarvedilolIvabradine

Intervention Hierarchy (Ancestors)

PropanolaminesAmino AlcoholsAlcoholsOrganic ChemicalsPropanolsAminesCarbazolesIndolesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic CompoundsHeterocyclic Compounds, 3-RingBenzazepines

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
PARTICIPANT
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 9, 2014

First Posted

November 19, 2014

Study Start

July 1, 2014

Primary Completion

August 31, 2016

Study Completion

August 31, 2016

Last Updated

February 8, 2018

Record last verified: 2016-02

Locations

IN(1)