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

NCT07322237 | Recruiting Phase 4 DMC

• 1 other identifier: PGI/IEC/2025/SPL-865
• Study Type: interventional
• Target: 400
• Locations: 1 country
• Sites: 1

Brief Summary

1. 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. 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. 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.

Conditions

Cirrhotic Cardiomyopathy; Empagliflozin; Cardiometabolic Risk Factors; Cirrhosis

Keywords

Empagliflozin in cirrhosis; Carvedilol in Cirrhosis; SGLT-2 inhibitor; Ascites; Diastolic heart failure; heart failure with preserved ejection fraction

Outcome Measures

Primary Outcomes (1)

• Composite end point of decompensation event and/or death

  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 Outcomes (17)

• Improvement in Cardiac Diastolic Function

  From enrolment through study completion, an average of 1 year

• Improvement in Cardiac Diastolic Function

  From enrolment through study completion, an average of 1 year

• Improvement in Cardiac Diastolic Function

  From enrolment through study completion, an average of 1 year

• Improvement in Cardiac Diastolic Function

  From enrolment through study completion, an average of 1 year

• Improvement in Cardiac Systolic Function

  From enrolment through study completion, an average of 1 year

Study Arms (2)

Experimental: Empagliflozin + Carvedilol-arm

ACTIVE COMPARATOR

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

Active Comparator: Carvedilol arm

ACTIVE COMPARATOR

* 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

Interventions

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.

Experimental: Empagliflozin + Carvedilol-arm

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

Active Comparator: Carvedilol arm

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Post Graduate Institute of Medical Education and Research, Chandigarh: lead

Study Sites (1)

PGIMER Chandigarh

Chandigarh, 160012, India

RECRUITING

MeSH Terms

Conditions

Fibrosis; Ascites; Heart Failure, Diastolic

Interventions

empagliflozin; Carvedilol

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Heart Failure; Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Carbazoles; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 3-Ring

Central Study Contacts

Madhumita Premkumar, MD DM

CONTACT

01722754777; drmadhumitap@gmail.com

Madumita Premkumar

CONTACT

01722754777

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Additional Professor

Model Details: Double Blind Placebo controlled Randomized Controlled Trial

Study Record Dates

• First Submitted: November 30, 2025
• First Posted: January 7, 2026
• Study Start: April 1, 2026
• Primary Completion (Estimated): January 30, 2029
• Study Completion (Estimated): June 30, 2029
• Last Updated: May 14, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

IN (1)