DICE Study- Diastolic Improvement With Carvedilol & Empagliflozin in Patients With Cirrhosis (DICE)

May 13, 2026 updated by: Madhumita Premkumar, Post Graduate Institute of Medical Education and Research, Chandigarh

Empagliflozin + Carvedilol vs. Carvedilol Alone for Patients With Cirrhosis and Left Ventricular Diastolic Dysfunction and Impact on Hepatic Decompensation and Survival: A Double-Blind Placebo-Controlled Randomized Controlled Trial

  1. This proposed double-blind placebo controlled randomized controlled trial incorporates recent advances in management of heart failure and portal hypertension using the SGLT-2 inhibitor i.e. EMPAGLIFLOZIN. The drug has been found to be useful in large trials on heart failure with preserved ejection fraction in the general population with improvement in MASLD progression, with improvement in body weight and hepatic steatosis but no change in liver fibrosis.
  2. Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been shown to reduce the development and progression of heart failure in patients with type 2 diabetes and in those with heart failure and a reduced and preserved ejection fraction. In patients with cirrhosis safety of empagliflozin in a dose of 10 mg has been demonstrated.
  3. Prevention of decompensation related events in cirrhosis is the key endpoint of any liver-directed therapy as the median survival in the compensated state exceeds 10 years but median survival in the decompensated state approximates 1.5 years. Previous data has demonstrated the risk of hepatic decompensation acute kidney injury and poor survival in patients with cirrhosis and heart failure with preserved ejection fraction (HFpEF) i.e. LVDD a large subset of whom meet criteria for CCM.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

New diagnostic criteria for cirrhotic cardiomyopathy For the diagnosis of cirrhotic cardiomyopathy (CCM) we will use criteria proposed by the CCM consortium in 2020 with modification to take septal e' and E/e' readings. In accordance with the recent CCM criteria 'systolic dysfunction is defined as an ejection fraction (EF) of 50% or less or an absolute value of GLS <18%. LVDD grade will be determined if 3 of the following 4 criteria are met: early diastolic trans mitral flow to early diastolic mitral annular velocity (E/e') ≥15 left atrial volume index (LAVI) >34 mL/m2 septal early diastolic mitral annular velocity (e') <7 cm/second or tricuspid regurgitation (TR) maximum velocity >2.8 m/second in the absence of pulmonary hypertension (HTN) and the presence of measurable early to late diastolic trans mitral flow velocity (E/A) ratio (E/A >2 = grade 3 E/A 0.8-2 = grade 2)'. LVDD will be classified as "of indeterminate grade" when only 2 of the 4 criteria are met. The supporting criteria for diagnosis of LVDD are changes in cardiac chamber sizes electrophysiological abnormalities increased biomarkers like N terminal pro-brain natriuretic peptide (NT-Pro BNP) and troponin I.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
400

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

  • Name: Madumita Premkumar
  • Phone Number: 01722754777

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion criteria

  • Age range of 18-65 years
  • Cirrhosis as diagnosed by histology or clinical laboratory and USG findings
  • LVDD (with EF>50%) on 2D echocardiography with TDI
  • Written informed consent.

Exclusion criteria

  • Age >65 years
  • Serum Creatinine>2 mg/dl
  • History of urinary tract /genital infections in last 3 months
  • Patient on treatment with statin (one month before the study)
  • Advanced Cirrhosis (MELD>20)
  • Coronary artery disease
  • Sick sinus syndrome/ Pacemaker valvular heart disease
  • Cardiac rhythm disorder Peripartum cardiomyopathy
  • Portopulmonary hypertension/ hepatopulmonary syndrome
  • Transjugular intrahepatic porto systemic shunt (TIPS) insertion
  • Hepatocellular carcinoma
  • Pregnancy or lactation
  • Patients with HIV or retroviral therapy
  • Anemia Hb < 8gm/dl in females and < 9 gm/dl in males
  • Acute variceal bleeding in last 6months.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Experimental: Empagliflozin + Carvedilol-arm

Experimental: Empagliflozin + Carvedilol-arm

  • Empagliflozin fixed dose of 10 mg per day in patients with or without diabetes for 1 year from randomization
  • Carvedilol: Starting dose of 3.125 mg twice daily targeted upwards q 7 days to achieve target heart rate
  • Standard Medical Therapy for liver disease as per clinician decision
Drug: Empagliflozin + Carvedilol

Patient Recruitment:

The study participants are all cirrhosis patients receiving treatment at PGIMER Chandigarh. Eligible participants meeting LVDD criteria per the CCM Consortium 2020 consensus.

Carvedilol Dosing protocol in this study Patients will be given carvedilol in a starting dose of 3.125 mg twice daily. The dose will be titrated weekly to achieve a target heart rate of 50-60/ min taking care that side effects such as hypotension bronchospasm excessive bradycardia are not seen. The maximum dosage allowed as per prior trial data is 25 mg per day.

Empagliflozin Dosing protocol in this Study:

• All patients will receive a standard dose of Empagliflozin fixed dose of 10 mg per day in patients with or without diabetes.
Active Comparator: Active Comparator: Carvedilol arm
  • Carvedilol: Starting dose of 3.125 mg twice daily targeted upwards q 7 days to achieve target heart rate 10 mg placebo administered once daily.
  • Standard Medical Therapy prescribed as per clinician decision
Drug: Carvedilol
  • Carvedilol: Starting dose of 3.125 mg twice daily targeted upwards q 7 days to achieve target heart rate 10 mg placebo pill
  • Standard Medical Therapy

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Composite end point of decompensation event and/or death
Time Frame: From enrolment through study completion, an average of 1 year
The primary outcome measure is defined as a composite end point of acute decompensation event (acute variceal bleeding new ascites or recurrence of previously controlled ascites episode of hepatic encephalopathy or acute kidney injury) OR all-cause death in patients with cirrhosis and LVDD
From enrolment through study completion, an average of 1 year

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Improvement in Cardiac Diastolic Function
Time Frame: From enrolment through study completion, an average of 1 year

Improvement in CCM parameters (left ventricular diastolic function) in either arm based on Echocardiography and Cardiac Imaging

Septal E/e' ratio
From enrolment through study completion, an average of 1 year
Improvement in Cardiac Diastolic Function
Time Frame: From enrolment through study completion, an average of 1 year
Improvement in CCM parameters (left ventricular diastolic function) in either arm based on Echocardiography and Cardiac Imaging Septal e' velocity
From enrolment through study completion, an average of 1 year
Improvement in Cardiac Diastolic Function
Time Frame: From enrolment through study completion, an average of 1 year

Improvement in CCM parameters (left ventricular diastolic function) in either arm based on Echocardiography and Cardiac Imaging

Left atrial volume index
From enrolment through study completion, an average of 1 year
Improvement in Cardiac Diastolic Function
Time Frame: From enrolment through study completion, an average of 1 year

Improvement in CCM parameters (left ventricular diastolic function) in either arm based on Echocardiography and Cardiac Imaging

Tricuspid regurgitant Velocity
From enrolment through study completion, an average of 1 year
Improvement in Cardiac Systolic Function
Time Frame: From enrolment through study completion, an average of 1 year
Improvement in Cardiac systolic function (Cardiac Index) in either arm based on Echocardiography and Cardiac Imaging
From enrolment through study completion, an average of 1 year
Improvement in Cardiac Systolic Function
Time Frame: From enrolment through study completion, an average of 1 year
Improvement in Cardiac systolic function (Ejection Fraction) in either arm based on Echocardiography and Cardiac Imaging
From enrolment through study completion, an average of 1 year
Improvement in Cardiac Systolic Function
Time Frame: From enrolment through study completion, an average of 1 year
Improvement in Cardiac systolic function (Global Longitudinal Strain) in either arm based on Echocardiography and Cardiac Imaging
From enrolment through study completion, an average of 1 year
Hospitalization events
Time Frame: From enrolment through study completion, an average of 1 year
• Episodes warranting hospitalization
From enrolment through study completion, an average of 1 year
• Serum level of NT-proBNP
Time Frame: At enrolment
Cardiac biomarkers
At enrolment
• Serum level of NT-proBNP
Time Frame: At 6 months from enrolment
Cardiac biomarkers
At 6 months from enrolment
• Serum level of NT-proBNP
Time Frame: At 12 months from enrolment
Cardiac biomarkers
At 12 months from enrolment
• Serum level of Galectin-3
Time Frame: At enrolment
Cardiac biomarkers
At enrolment
• Serum level of Galectin 3
Time Frame: At 6 months from enrolment
Cardiac biomarkers
At 6 months from enrolment
• Serum level of Galectin 3
Time Frame: At 12 months from enrolment
Cardiac biomarkers
At 12 months from enrolment
• Serum level of Aldosterone
Time Frame: At enrolment
Cardiac biomarkers
At enrolment
• Serum level of Aldosterone
Time Frame: At 6 months from enrolment
Cardiac biomarkers- Renin angiotensin aldosterone system
At 6 months from enrolment
• Serum level of Aldosterone
Time Frame: At 12 months from enrolment
Cardiac biomarkers- Renin angiotensin aldosterone system
At 12 months from enrolment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Post Graduate Institute of Medical Education and Research, Chandigarh

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 1, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 30, 2029

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 30, 2029

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 30, 2025

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 22, 2025

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 7, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 14, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 13, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • PGI/IEC/2025/SPL-865

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

This database has identifier information

Drug and device information, study documents

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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