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NCT Number: NCT07322237

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

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.

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Key information

Conditions

Cirrhotic Cardiomyopathy Ascites Cardiometabolic Risk Factors Cardiovascular Diseases Cirrhosis Empagliflozin Fibrosis Heart Diseases Heart Failure Heart Failure, Diastolic Pathologic Processes Pathological Conditions, Signs and Symptoms

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Empagliflozin + Carvedilol

Drug

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.

Carvedilol

Drug
  • 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

Primary outcomes

  1. 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

Secondary outcomes

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. Hospitalization events

    Time frame: From enrolment through study completion, an average of 1 year

    • Episodes warranting hospitalization

  9. • Serum level of NT-proBNP

    Time frame: At enrolment

    Cardiac biomarkers

  10. • Serum level of NT-proBNP

    Time frame: At 6 months from enrolment

    Cardiac biomarkers

  11. • Serum level of NT-proBNP

    Time frame: At 12 months from enrolment

    Cardiac biomarkers

  12. • Serum level of Galectin-3

    Time frame: At enrolment

    Cardiac biomarkers

  13. • Serum level of Galectin 3

    Time frame: At 6 months from enrolment

    Cardiac biomarkers

  14. • Serum level of Galectin 3

    Time frame: At 12 months from enrolment

    Cardiac biomarkers

  15. • Serum level of Aldosterone

    Time frame: At enrolment

    Cardiac biomarkers

  16. • Serum level of Aldosterone

    Time frame: At 6 months from enrolment

    Cardiac biomarkers- Renin angiotensin aldosterone system

  17. • Serum level of Aldosterone

    Time frame: At 12 months from enrolment

    Cardiac biomarkers- Renin angiotensin aldosterone system

Study contacts

Contact information is provided by the study sponsor or research team.

Madhumita Premkumar, MD DM

CONTACT

[email protected]

01722754777

Madumita Premkumar

CONTACT

01722754777

Sponsors and collaborators

Lead sponsor

Post Graduate Institute of Medical Education and Research, Chandigarh

Other

Registry information

Official study title

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

Acronym: DICE

Important dates

Study start
2026
Primary completion
2029
Study completion
2029
First posted
Jan 7, 2026
Registry last updated
May 14, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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